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Participants between the ages of 10-86 years old were vaccinated with split-inactivated influenza vaccine (Fluzone®) in six consecutive influenza seasons from 2016-2017 to 2021-2022. Vaccine effectiveness varies from season to season as a result of both host immune responses as well as evolutionary changes in the influenza virus surface glycoproteins that provide challenges to vaccine manufacturers to produce more effective annual vaccines. Next generation influenza vaccines are in development and may provide protective immune responses against a broader number of influenza viruses and reduce the need for annual vaccination. An improved understanding how current influenza vaccines are influenced by human host immune responses in people of different ages and co-morbidities is necessary for designing the next-generation of 'universal' or broadly-protective influenza vaccines. Overall, pre-existing immune responses to previous influenza virus exposures, either by past infections or vaccinations, is a critical factor influencing host responses to seasonal influenza vaccination. Participants vaccinated in consecutive seasons had reduced serum hemagglutination-inhibition (HAI) activity against strains included in the vaccine compared to participants that had not been vaccinated in the preceding 1-2 years prior to entering this study. The magnitude and breadth of these antibody responses were also modulated by the age of the participant. Elderly participants over 65 years of age, in general, had lower pre-existing HAI titers each season prior to vaccination with lower post-vaccination titers compared to children or young adults under the age of 35. The administration of higher doses (HD) of the split-inactivated vaccine enhanced the antibody titers in the elderly. This report showcases 6 consecutive years of antibody HAI activity in human subjects receiving seasonal split-inactivated influenza vaccine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Carlock et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response., Competing Interests: Authors YS and ZY were employed by the company Wuhan Institute of Biological Products Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Wang, Yang, He, Bao, Xie, Sun, Li, Quan, Yang and Li.)

Background: Scale drop disease virus (SDDV) threatens Asian seabass (Lates calcarifer) aquaculture production by causing scale drop disease (SDD) in Asian seabass. Research on the development of SDDV vaccines is missing an in-depth examination of long-term immunity and the immune reactions it provokes. This study investigated the long-term immune protection and responses elicited by an SDDV vaccine. The research evaluated the effectiveness of a formalin-inactivated SDDV vaccine (SDDV-FIV) using both prime and prime-booster vaccination strategies in Asian seabass. Three groups were used: control (unvaccinated), single-vaccination (prime only), and booster (prime and booster). SDDV-FIV was administered via intraperitoneal route, with a booster dose given 28 days post-initial vaccination., Results: The immune responses in vaccinated fish (single and booster groups) showed that SDDV-FIV triggered both SDDV-specific IgM and total IgM production. SDDV-specific IgM levels were evident until 28 days post-vaccination (dpv) in the single vaccination group, while an elevated antibody response was maintained in the booster group until 70 dpv. The expression of immune-related genes (dcst, mhc2a1, cd4, ighm, cd8, il8, ifng, and mx) in the head kidney and peripheral blood lymphocytes (PBLs) of vaccinated and challenged fish were significantly upregulated within 1-3 dpv and post-SDDV challenge. Fish were challenged with SDDV at 42 dpv (challenge 1) and 70 dpv (challenge 2). In the first challenge, the group that received booster vaccinations demonstrated notably higher survival rates than the control group (60% versus 20%, P < 0.05). However, in the second challenge, while there was an observable trend towards improved survival rates for the booster group compared to controls (42% versus 25%), these differences did not reach statistical significance (P > 0.05). These findings suggest that the SDDV-FIV vaccine effectively stimulates both humoral and cellular immune responses against SDDV. Booster vaccination enhances this response and improves survival rates up to 42 dpv., Conclusions: This research provides valuable insights into the development of efficient SDDV vaccines and aids in advancing strategies for immune modulation to enhance disease management in the aquaculture of Asian seabass., (© 2024. The Author(s).)

Objective: Porcine interferon-γ (poIFN-γ) and porcine granulocyte-macrophage colony-stimulating factor (poGM-CSF) are multifunctional cytokines that exhibit robust antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV). In this study, the immunoadjuvant effects of recombinant poIFN-γ-poGM-CSF fusion protein in inactivated PRRSV vaccine administered to piglets were assessed., Animals: Twenty-eight 4-week-old specific pathogen-free piglets., Methods: The experimental piglets were divided into control, highly pathologic PRRSV, PRRSV killed virus vaccine (KV), poIFN-γ-poGM-CSF, KV + 1.0 mg poIFN-γ-poGM-CSF, KV + 2.0 mg poIFN-γ-poGM-CSF, and KV + 4.0 mg poIFN-γ-poGM-CSF groups. A recombinant poIFN-γ-linker-poGM-CSF fusion gene was constructed via splicing by overlap extension PCR and prepared using an Escherichia coli expression system, after which its adjuvant activity in the context of PRRSV KV administration was assessed., Results: This analysis revealed the successful construction of the poIFN-γ-linker-poGM-CSF fusion gene via splicing by overlap extension PCR, with recombinant poIFN-γ-linker-poGM-CSF successfully being prepared in E coli with a plasmid vector for expressing thioredoxin fusion proteins with an enterokinase site. Importantly, the coadministration of poIFN-γ-linker-poGM-CSF and PRRSV KV significantly increased neutralizing antibody titers, accelerated viral clearance, reduced clinical symptoms, and prevented highly pathogenic PRRSV infection., Clinical Relevance: The recombinant poIFN-γ-poGM-CSF fusion protein is a promising candidate adjuvant for use in the context of swine immunization and viral challenge.

Background: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate., Objectives: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response., Methods: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination., Results: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4 + T cells, and CD8 + T cells using LASSO combined with the random forest algorithm., Conclusion: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs., Methods: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed., Results: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval., Conclusions: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807., Competing Interests: Potential conflicts of interest . E. J. A. has consulted for Pfizer, Sanofi Pasteur, GSK, Janssen, Moderna, and Medscape, and his institution has received funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi-Pasteur, Janssen, and Micron. He has served on a safety monitoring board for Kentucky BioProcessing, Inc. and Sanofi Pasteur. He has served on a data adjudication board for WCG and ACI Clinical. His institution has also received funding from the National Institutes of Health (NIH) to conduct clinical trials of COVID-19 vaccines. He is currently employed by Moderna, Inc. N. R. has consulted for EMMES, Moderna, GSK, Sanofi, Seqirus, and ICON, and her institution receives funds to conduct clinical research unrelated to this manuscript from Pfizer, Sanofi, Quidel, Lilly, Immorna, Vaccine Company, and Merck as well as NIH to conduct translational clinical studies and interventional clinical trials. P. W. has consulted for EMMES and Pfizer and her institution has received funds to conduct clinical research unrelated to this manuscript from Pfizer, Glaxo Smith Kline, Sanofi-Pasteur, and Gilead as well as NIH. C. A. R.'s institution has received funds to conduct clinical research unrelated to this manuscript from the Centers for Disease Control and Prevention, BioFire Inc, GSK, MedImmune, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, and Sanofi-Pasteur. She is co-inventor of patented respiratory syncytial virus vaccine technology, which has been licensed to Meissa Vaccines, Inc. C. M. K.'s institution has received funds to conduct clinical research unrelated to this manuscript from the CDC, Pfizer, Merck, and the NIH to conduct clinical trials of the Moderna COVID-19 vaccine. V. R. is currently employed by Pfizer, Inc., and works in vaccine clinical research unrelated to the current manuscript. This material reflects the personal views of the author and may not reflect the views of her current employer. M. J. M. reported these potential competing interests: laboratory research and clinical trials contracts for vaccines or MAB with Lilly, Pfizer, and Sanofi; contract funding from USG/HHS/BARDA for research specimen characterization and repository; research grant funding from USG/HHS/NIH for vaccine and MAB clinical trials; personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc., and Pfizer. EBW has received funding support from Pfizer, Moderna, Sequiris, Najit Technologies Inc, and Clinetic for the conduct of clinical trials and clinical research. E. B. W. has served as an advisor to Vaxcyte and consultant to ILiAD biotechnologies. A. C. S.'s institution has received funds to conduct clinical research unrelated to this manuscript from NIH, HIV Vaccine Trials Network, COVID Vaccine Prevention Network, International AIDS Vaccine Initiative, Crucell/Janssen, Moderna, Pfizer, and Sanofi-Pasteur. S. K.'s institution has received funds to conduct clinical research and vaccine trials unrelated to this manuscript from the CDC, Pfizer, Meissa, Emergent BioSolutions, and the NIH. I. Y. reported being a member of the NIAID/COVPN mRNA-1273 Study Group and her institution received funding to conduct clinical research from NIH, Gates Foundation, Centers for Disease Control and Prevention, Pfizer, and Moderna outside the submitted work. She has consulted for Merck, Sanofi-Pasteur, and UptoDate. S. E. F. has received funding to conduct research from Novartis, Moderna, Janssen, Pfizer, and Bavarian Nordic and is a member of the HIV Vaccine Trials Network safety monitoring board. G. A. has received funding to conduct research from Bavarian Nordic. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn 2+ ) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn 2+ -loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn 2+ -loaded nanoadjuvant for veterinary vaccines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Immersion vaccination, albeit easier to administer than immunization by injection, sometimes has challenges with antigen uptake, resulting in sub-optimal protection. In this research, a new strategy to enhance antigen uptake of a heat-inactivated Vibrio harveyi vaccine in Asian seabass (Lates calcarifer) using oxygen nanobubble-enriched water (ONB) and positively charged chitosan (CS) was explored. Antigen uptake in fish gills was assessed, as was the antibody response and vaccine efficacy of four different combinations of vaccine with ONB and CS, and two control groups. Pre-mixing of ONB and CS before introducing the vaccine, referred to as (ONB + CS) + Vac, resulted in superior antigen uptake and anti-V. harveyi antibody (IgM) production in both serum and mucus compared to other formulas. The integration of an oral booster (4.22 × 10 8  CFU/g, at day 21-25) within a vaccine trial experiment set out to further evaluate how survival rates post exposure to V. harveyi might be improved. Antibody responses were measured over 42 days, and vaccine efficacy was assessed through an experimental challenge with V. harveyi. The expression of immune-related genes IL1β, TNFα, CD4, CD8, IgT and antibody levels were assessed at 1, 3, and 7-day(s) post challenge (dpc). The results revealed that antibody levels in the group (ONB + CS) + Vac were consistently higher than the other groups post immersion immunization and oral booster, along with elevated expression of immune-related genes after challenge with V. harveyi. Ultimately, this group demonstrated a significantly higher relative percent survival (RPS) of 63 % ± 10.5 %, showcasing the potential of the ONB-CS-Vac complex as a promising immersion vaccination strategy for enhancing antigen uptake, stimulating immunological responses, and improving survival of Asian seabass against vibriosis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study longitudinally evaluated the immune response in individuals over a year after receiving three doses of an inactivated SARS-CoV-2 vaccine, focusing on reactions to Omicron breakthrough infections. From 63 blood samples of 37 subjects, results showed that the third booster enhanced the antibody response against Alpha, Beta, and Delta VOCs but was less effective against Omicron. Although antibody titres decreased post-vaccination, SARS-CoV-2-specific T-cell responses, both CD4 + and CD8 + , remained stable. Omicron breakthrough infections significantly improved neutralization against various VOCs, including Omicron. However, the boost in antibodies against WT, Alpha, Beta, and Delta variants was more pronounced. Regarding T cells, breakthrough infection predominantly boosted the CD8 + T-cell response, and the intensity of the spike protein-specific T-cell response was roughly comparable between WT and Omicron BA.5., (© 2024 The Authors. Immunology published by John Wiley & Sons Ltd.)

Our study aimed to evaluate the safety of CoronaVac, an inactivated vaccine made by Sinovac, in children aged 7-14. We conducted a parent-administered online survey to monitor adverse reactions after vaccinating children in Taizhou, China, from February 15, 2021, to January 19, 2022. 767 parents completed the survey after receiving a questionnaire via WeChat. Overall, 15.3 % (117/767) of children experienced adverse effects after the first dose, and 12.2 % (88/724) after the second. Muscle pain was the most common adverse reaction post-first dose (10.0 %), while localized pain or itching at the injection site was most common after the second dose (7.6 %). In conclusion, the vaccine has a low incidence of side effects. The mild to moderate, transient, and common nature of these effects further boosts parents' confidence in vaccinating their children., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Previous research suggested that the inactivated influenza vaccine (IIV) may protect against SARS-CoV-2 infection or a severe course of COVID-19. These findings were however based on cohort studies, that are prone to confounding by indication. We examined the association between IIV and SARS-Cov-2 infection in a Dutch population using a test-negative design., Methods: This test-negative case-control study was conducted in adults (≥60) who tested because of COVID-19 like symptoms at community SARS-CoV-2 testing locations in the Netherlands during the period of November 8th 2021-March 11th 2022. Information on receipt of IIV in October-November 2021 was routinely collected at each visit. Logistic regression was used to calculate unadjusted, partially (sex, age, education level) and fully adjusted (COVID-19 vaccination, IIV 2020) odds ratios (ORs) for receipt of IIV in SARS-CoV-2 positive versus negative subjects. Differential effects on SARS-CoV-2 risk by time since IIV were investigated by including an interaction term for calendar time: November 2021-January 2022 vs February-March 2022., Results: In total, 1,832 participants were included in the main analysis, of whom 336 (18.3 %) had a positive SARS-CoV-2 test. No significant association between IIV and SARS-CoV-2 infection was found; fully adjusted OR of 1.07 (95 % CI: 0.78-1.49). The interaction term for time periods was not significant (1.04 [95 % CI: 0.51-2.15], p = 0.91). Results were robust in sensitivity analyses., Conclusions: While earlier observational studies suggested a protective non-specific effect of IIV and SARS-CoV-2 infections, this smaller, but well controlled test-negative design study does not suggest an effect, either positive or negative. Larger test-negative design studies, or alternative designs such as the self-controlled case series design are needed to confirm these findings and provide more definite answers on the topic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier India Pvt Ltd. Published by Elsevier Ltd. All rights reserved.)

Little studies evaluated the effectiveness of booster vaccination of inactivated COVID-19 vaccines against being infected (susceptibility), infecting others (infectiousness), and spreading the disease from one to another (transmission). Therefore, we conducted a retrospective cohort study to evaluate the effectiveness of booster vaccination of inactivated COVID-19 vaccines against susceptibility, infectiousness, and transmission in Shenzhen during an Omicron BA.2 outbreak period from 1 February to 21 April 2022. The eligible individuals were classified as four sub-cohorts according to the inactivated COVID-19 vaccination status of both the close contacts and their index cases: group 2-2, fully vaccinated close contacts seeded by fully vaccinated index cases (reference group); group 2-3, booster-vaccinated close contacts seeded by fully vaccinated index cases; group 3-2, fully vaccinated close contacts seeded by booster-vaccinated index cases; and group 3-3, booster-vaccinated close contacts seeded by booster-vaccinated index cases. Univariate and multivariate logistic regression analyses were applied to estimate the effectiveness of booster vaccination. The sample sizes of groups 2-2, 2-3, 3-2, and 3-3 were 846, 1,115, 1,210, and 2,417, respectively. We found that booster vaccination had an effectiveness against infectiousness of 44.9% (95% CI: 19.7%, 62.2%) for the adults ≥ 18 years, 62.2% (95% CI: 32.0%, 78.9%) for the female close contacts, and 60.8% (95% CI: 38.5%, 75.1%) for the non-household close contacts. Moreover, booster vaccination had an effectiveness against transmission of 29.0% (95% CI: 3.2%, 47.9%) for the adults ≥ 18 years, 38.9% (95% CI: 3.3%, 61.3%) for the female close contacts, and 45.8% (95% CI: 22.1%, 62.3%) for the non-household close contacts. However, booster vaccination against susceptibility did not provide any protective effect. In summary, this study confirm that booster vaccination of the inactivated COVID-19 vaccines provides low level of protection and moderate level of protection against Omicron BA.2 transmission and infectiousness, respectively. However, booster vaccination does not provide any protection against Omicron BA.2 susceptibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liao, Su, Zhao, Qin, Zhang, Gao, Wan, Liao, Zou and He.)

Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges posed by transboundary diseases in which viral infections are at the forefront. Among the porcine viral diseases, African swine fever, classical swine fever, foot and mouth disease, porcine reproductive and respiratory syndrome, pseudorabies, swine influenza, and transmissible gastroenteritis are some of the diseases that cause substantial economic losses in the pig industry. It is a well-established fact that vaccination is undoubtedly the most effective strategy to control viral infections in animals. From the period of Jenner and Pasteur to the recent new-generation technology era, the development of vaccines has contributed significantly to reducing the burden of viral infections on animals and humans. Inactivated and modified live viral vaccines provide partial protection against key pathogens. However, there is a need to improve these vaccines to address emerging infections more comprehensively and ensure their safety. The recent reports on new-generation vaccines against swine viruses like DNA, viral-vector-based replicon, chimeric, peptide, plant-made, virus-like particle, and nanoparticle-based vaccines are very encouraging. The current review gathers comprehensive information on the available vaccines and the future perspectives on porcine viral vaccines.

Background: To investigate the immune responses and protection ability of ultraviolet light (UV)-inactivated recombinant vesicular stomatitis (rVSV)-based vectors that expressed a fusion protein consisting of four copies of the influenza matrix 2 protein ectodomain (tM2e) and the Dendritic Cell (DC)-targeting domain of the Ebola Glycoprotein (EΔM), (rVSV-EΔM-tM2e)., Method: In our previous study, we demonstrated the effectiveness of rVSV-EΔM-tM2e to induce robust immune responses against influenza M2e and protect against lethal challenges from H1N1 and H3N2 strains. Here, we used UV to inactivate rVSV-EΔM-tM2e and tested its immunogenicity and protection in BALB/c mice from a mouse-adapted H1N1 influenza challenge. Using Enzyme-Linked Immunosorbent Assay (ELISA) and Antibody-Dependent Cellular Cytotoxicity (ADCC), the influenza anti-M2e immune responses specific to human, avian and swine influenza strains induced were characterized. Likewise, the specificity of the anti-M2e immune responses induced in recognizing M2e antigen on the surface of the cell was investigated using Fluorescence-Activated Cell Sorting (FACS) analysis., Results: Like the live attenuated rVSV-EΔM-tM2e, the UV-inactivated rVSV-EΔM-tM2e was highly immunogenic against different influenza M2e from strains of different hosts, including human, swine, and avian, and protected against influenza H1N1 challenge in mice. The FACS analysis demonstrated that the induced immune responses can recognize influenza M2 antigens from human, swine and avian influenza strains. Moreover, the rVSV-EΔM-tM2e also induced ADCC activity against influenza M2e from different host strains., Conclusions: These findings suggest that UV-inactivated rVSV-EΔM-tM2e could be used as an inactivated vaccine against influenza viruses., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: Cell-based quadrivalent-inactivated influenza vaccine has been shown to have higher vaccine effectiveness than traditional egg-based quadrivalent-inactivated influenza vaccine. This is observed despite similar levels of serum hemagglutinin antibodies induced by each vaccine., Methods: In this study, we examine peripheral immune activation after egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated, and ribonucleic acid was sequenced from 81 study participants (41 Fluzone, egg based and 40 Flucelvax, cell based) pre- and 7 days postvaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted., Results: Cell-based influenza vaccine induced greater interferon-stimulated and innate immune gene activation compared with egg-based influenza vaccine. Participants who seroconverted had increased interferon-signaling activation versus those who did not seroconvert., Conclusions: These data suggest that cell-based influenza vaccine stimulates immune activation differently from egg-based influenza vaccine, shedding light on reported differences in vaccine effectiveness., Competing Interests: Potential conflicts of interest . All authors: The authors have ongoing relationships with the NIH and CDC as stated in the financial support section. The authors have a previous funding relationship with Sanofi Pasteur Inc., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines., Methods: The primary immunogenicity objective of this phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy adults aged ≥65 years in Australia was to demonstrate noninferiority of immune responses with coadministration of the stabilized RSV prefusion F protein-based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone, using a 1.5-fold noninferiority margin (lower bound 95% confidence interval >.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data., Results: Of 1403 participants randomized, 1399 received vaccinations (median age, 70; range, 65‒91 years). Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin., Conclusions: The primary study objectives were met, demonstrating noninferiority of RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV and that RSVpreF had an acceptable safety and tolerability profile when coadministered with SIIV. The results of this study support coadministration of RSVpreF and SIIV in an older-adult population., Clinical Trials Registration: https://clinicaltrials.gov/study/NCT05301322., Competing Interests: Potential conflicts of interest. E. A. reports receiving consulting fees from Moderna for vaccine advisory meeting. R. J. S. reports being an investigator for Pfizer (consultant doctor/medical investigator for the University of the Sunshine Coast Clinical Trials team; received consulting fees to work as a medical investigator; and was involved with the conduct of the clinical trial for Pfizer RSVpreF vaccine at the clinical trial site in Queensland, Australia). A. G. reports patents planned, issued, or pending: WO2017/1096729. All authors (except E. A. and R. J. S.) are employees of Pfizer, Inc, and may hold stock or stock options. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19., (© 2024. The Author(s).)

Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira, continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pseudorabies virus (PRV) is a highly contagious viral disease, which leads to severe financial losses in the breeding industry worldwide. Presently, PRV is mainly controlled using live attenuated and inactivated vaccines. However, these vaccines have an innate tendency to lose their structural conformation upon exposure to environmental and chemical stressors and cannot provide full protection against the emerging prevalent PRV variants. In this work, first, we synthesized aminated ZIF-7/8 nanoparticles (NPs), and then chemical bond-coated alginate dialdehyde (ADA, a type of dioxide alginate saccharide) on their surface via Schiff base reaction to obtain ZIF-7/8-ADA NPs. The as-fabricated ZIF-7/8-ADA NPs exhibited high stability, monodispersity and a high loading ratio of antigen. Furthermore, the ZIF-7/8-ADA NPs showed good biocompatibility in vitro and in vivo . Using ZIF-7/8-ADA NPs as an adjuvant and inactivated PRV as a model antigen, we constructed a PR vaccine through a simple mixture. The immunity studies indicated that ZIF-7/8-ADA induced an enhancement in the Th1/Th2 immune response, which was superior to that of the commercial ISA201, alum adjuvant and ZIF-7/8. Due to the pH-sensitive release of the antigen in lysosomes, the as-prepared PR vaccine subsequently accelerated the antigen presentation and improved the immune responses in vitro and in vivo . The results of PRV challenge using mice as the model demonstrated that ZIF-7/8-ADA achieved the same preventive effect as the commercial ISA201 and was much better than the alum adjuvant, and thus can serve as a promising delivery system and adjuvant to enhance humoral and cellular responses against PRV infection.

Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection., (© 2024. The Author(s).)

Strangles is a highly contagious disease of the equine upper respiratory tract caused by Streptococcus equi subspecies. Streptococcus equi subsp. equi (S. equi) and Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) was isolated, as local, hot, and field strains, from horses clinically suffering from respiratory distress. The isolated Streptococci were identified using bacteriological and molecular techniques. Four formulations of inactivated S. equi vaccines were developed and evaluated. The first formulation was prepared using the S. equi isolates, adjuvanted with MONTANIDE GEL adjuvant, while the second formulation was adjuvanted with MONTANIDE ISA-70 adjuvant. The other 2 formulations were inactivated combined vaccines prepared from both S. equi and S. zooepidemicus isolates. The 3rd formulation was the combined isolates adjuvanted with MONTANIDE GEL while the 4th formulation was the combined isolates adjuvanted with MONTANIDE ISA-70. The developed vaccines' physical properties, purity, sterility, safety, and potency were ensured. The immunizing efficacy was determined in isogenic BALB/c mice and white New Zealand rabbits using the passive hemagglutination test. Also, the antibodies' titer of the combined S. equi and S. zooepidemicus vaccine adjuvanted with MONTANIDE ISA-70 in foals was tracked using an indirect enzyme-linked immunosorbent assay. The protective efficacy of the developed vaccines was determined using a challenge test in both laboratory and field animal models, where a 75% protection rate was achieved. The combined vaccine proved to be more efficacious than the monovalent vaccine. Also, the MONTANIDE ISA-70 adjuvant provided significant protective efficacy than the MONTANIDE GEL. The current work is introducing a very promising mitigative and strategic controlling solution for strangles., (© 2024. The Author(s).)

Background: A global shortage of cholera vaccines has increased the use of single-dose regimens, rather than the standard two-dose regimen. There is sparse evidence on single-dose protection, particularly in children. In 2020, a mass vaccination campaign was conducted in Uvira, an endemic urban setting in eastern Democratic Republic of the Congo, resulting in largely single-dose coverage. We examined the effectiveness of a single-dose of the oral cholera vaccine Euvichol-Plus in this high-burden setting., Methods: In this matched case-control study, we recruited individuals with medically attended confirmed cholera in the two cholera treatment facilities in the city of Uvira. The control group consisted of age-matched, sex-matched, and neighbourhood-matched community individuals. We recruited across two distinct periods: Oct 14, 2021, to March 10, 2022 (12-17 months after vaccination), and Nov 21, 2022, to Oct 18, 2023 (24-36 months after vaccination). Study staff administered structured questionnaires to all participants to capture demographics, household conditions, potential confounding variables, and vaccination status. The odds of vaccination for the case and control groups were contrasted in conditional logistic regression models to estimate unadjusted and adjusted vaccine effectiveness., Findings: We enrolled 658 individuals with confirmed cholera and 2274 matched individuals for the control group. 99 (15·1%) individuals in the case group were younger than 5 years at the time of vaccination. The adjusted single-dose vaccine effectiveness was 52·7% (95% CI 31·4 to 67·4) 12-17 months after vaccination and 44·7% (24·8 to 59·4) 24-36 months after vaccination. Although protection in the first 12-17 months after vaccination was similar for children aged 1-4 years and older individuals, the estimate of protection in children aged 1-4 years appeared to wane during the third year after vaccination (adjusted vaccine effectiveness 32·9%, 95% CI -30·7 to 65·5), with CIs spanning the null., Interpretation: A single dose of Euvichol-Plus provided substantial protection against medically attended cholera for at least 36 months after vaccination in this cholera-endemic setting. Although the evidence provides support for similar levels of protection in young children and others in the short term, protection among children younger than 5 years might wane significantly during the third year after vaccination., Funding: Wellcome Trust and Gavi, the Vaccine Alliance., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The newly emerged SARS-CoV-2 possesses shared antigenic epitopes with other human coronaviruses. We investigated if COVID-19 vaccination or SARS-CoV-2 infection may boost cross-reactive antibodies to other human coronaviruses., Methods: Prevaccination and postvaccination sera from SARS-CoV-2 naïve healthy subjects who received three doses of the mRNA vaccine (BioNTech, BNT) or the inactivated vaccine (CoronaVac, CV) were used to monitor the level of cross-reactive antibodies raised against other human coronaviruses by enzyme-linked immunosorbent assay. In comparison, convalescent sera from COVID-19 patients with or without prior vaccination history were also tested. Pseudoparticle neutralization assay was performed to detect neutralization antibody against MERS-CoV., Results: Among SARS-CoV-2 infection-naïve subjects, BNT or CV significantly increased the anti-S2 antibodies against Betacoronaviruses (OC43 and MERS-CoV) but not Alphacoronaviruses (229E). The prevaccination antibody response to the common cold human coronaviruses did not negatively impact the postvaccination antibody response to SARS-CoV-2. Cross-reactive antibodies that binds to the S2 protein of MERS-CoV were similarly detected from the convalescent sera of COVID-19 patients with or without vaccination history. However, these anti-S2 antibodies do not possess neutralizing activity in MERS-CoV pseudoparticle neutralization tests., Conclusions: Our results suggest that SARS-CoV-2 infection or vaccination may potentially modulate population immune landscape against previously exposed or novel human coronaviruses. The findings have implications for future sero-epidemiological studies on MERS-CoV., (© 2024 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

The enterovirus A71 (EV71) inactivated vaccine is an effective intervention to control the spread of the virus and prevent EV71-associated hand, foot, and mouth disease (HFMD). It is widely administered to infants and children in China. The empty particles (EPs) and full particles (FPs) generated during production have different antigenic and immunogenic properties. However, the antigen detection methods currently used were established without considering the differences in antigenicity between EPs and FPs. There is also a lack of other effective analytical methods for detecting the different particle forms, which hinders the consistency between batches of products. In this study, we analyzed the application of sedimentation velocity analytical ultracentrifugation (SV-AUC) in characterizing the EPs and FPs of EV71. Our results showed that the proportions of the two forms could be quantified simultaneously by SV-AUC. We also determined the repeatability and accuracy of this method and found that both parameters were satisfactory. We assessed SV-AUC for bulk vaccine quality control, and our findings indicated that SV-AUC can be used effectively to analyze the percentage of EPs and FPs and monitor the consistency of the process to ensure the quality of the vaccine.

Patients with inborn errors of immunity (IEI) are among the high-risk groups regarding COVID-19. Receiving booster doses (third and fourth) in addition to the standard doses is recommended in these patients. This study investigated the antibody response before and after a booster dose of Sinopharm vaccine in IEI patients.  Thirty patients (>12 years) with antibody deficiencies, referred to Imam Khomeini Hospital and Children's Medical Center in Tehran, were enrolled in this prospective cross-sectional study. All patients were fully vaccinated with the BBIBP-CorV vaccine (2 doses of Sinopharm). Initial measurements of anti-receptor-binding domain (anti-RBD) and anti-nucleocapsid (anti-N) IgG antibody responses were conducted by enzyme-linked immunosorbent assay (ELISA). Subsequently, all patients received a booster dose of the vaccine. Four to six weeks after booster injection, the levels of antibodies were re-evaluated.  Twenty patients with common variable immunodeficiency (CVID), 7 cases with agammaglobulinemia and 3 patients with hyper IgM syndrome were studied. Anti-RBD IgG and anti-N IgG antibodies increased in all patients after the booster. Our results indicated the need of receiving booster doses of the COVID-19 vaccine in patients with antibody deficiencies, even for enhancing humoral immune response specially in patients with CVID.

The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.) vaccines against RSV have been approved for elderly and pregnant women. Noninvasive mucosal vaccination, e.g., by inhalation, offers an alternative against respiratory pathogens like RSV. Effective mucosal vaccines induce local immune responses, potentially resulting in the efficient and fast elimination of respiratory viruses after natural infection. To investigate this immune response to an RSV challenge, low-energy electron inactivated RSV (LEEI-RSV) was formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) or 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DD-LEEI-RSV) for vaccination of mice intranasally. As controls, LEEI-RSV and formalin-inactivated-RSV (FI-RSV) were used via i.m. vaccination. The RSV-specific immunogenicity of the different vaccines and their protective efficacy were analyzed. RSV-specific IgA antibodies and a statistically significant reduction in viral load upon challenge were detected in mucosal DD-LEEI-RSV-vaccinated animals. Alhydrogel-adjuvanted LEEI-RSV i.m. showed a Th2-bias with enhanced IgE, eosinophils, and lung histopathology comparable to FI-RSV. These effects were absent when applying the mucosal vaccines highlighting the potential of DD-LEEI-RSV as an RSV vaccine candidate and the improved performance of this mucosal vaccine candidate., Competing Interests: SU and MT are authors of patents and patent applications covering LEEI to inactivate liquids: WO2018041953, DE102015224206B3, US10080795, DE 102017002645.9. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eberlein, Rosencrantz, Finkensieper, Besecke, Mansuroglu, Kamp, Lange, Dressman, Schopf, Hesse, Thoma, Fertey, Ulbert and Grunwald.)

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs., (© 2024. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Importance: Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay., Objective: To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment., Design, Setting, and Participants: This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023., Exposures: Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year)., Main Outcomes and Measures: Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed., Results: Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment., Conclusions and Relevance: The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.

This study aimed to examine the safety, immunogenicity and protective effective of inhaled COVID-19 vaccines (ICVs). Literature research was done through EMBASE, Cochrane, PubMed, and Web of Science up to 10 March 2024. Pooled estimates with corresponding 95% confidence intervals (CI) were computed and compared using the random effects and common effects model. Of the 15 studies, 11 analyzed safety, 13 analyzed immunogenicity, and 3 analyzed protective effective. The results showed a favorable safety profile of ICVs for primary vaccination series, however it does not always seem to produce the expected immune response and protective effective. Meta-analysis of ICVs booster vaccinations (BVs) showed that the levels of neutralizing antibody Geometric mean titer (nAb-GMT) with aerosolised Ad5-nCoV (AAd5-nCoV) were all higher than those with inactivated vaccine (INA-nCoV) (standard mean difference (SMD) = 2.32; 95% CI: 1.96-2.69) and intramuscular Ad5-nCoV (IMAd5-nCoV) (SMD = 0.31; 95% CI: 0.14-0.48) against the original strain of SARS-CoV-2. Importantly, we also observed similar results in the omicron variant. In addition, ICV in BVs has high mucosal immunity to IgA antibodies. The risk of adverse events was comparable or lower for AAd5-nCoV compared to INA-nCoV or IMAd5-nCoV. Current evidence shows that the safety profile of ICVs were well. The booster dose of AAd5-nCoV had a high immune response (including mucosal immunity) and provided protection against COVID-19 caused by the SARS-CoV-2 omicron variant. Further studies are needed to investigate the long-term safety of intranasal vaccine booster protection and various types of ICVs., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Staphylococcus aureus, Escherichia coli and Mycoplasma bovis are the most commonly isolated mastitis pathogens. The aim of this study was to evaluate the efficacy of a new mixed vaccine against mastitis caused by  Staphylococcus aureus, Escherichia coli, and Mycoplasma bovis. For this purpose, a mixed inactivated vaccine was administered subcutaneously to 24 heifers as one dose (2 mL) on the 45th day before birth and the second dose 21 days later. In 9 heifers, 2 mL of PBS was administered as placebo instead of vaccine. Then, heifers were divided into 3 groups as 7 vaccinated and 3 unvaccinated animals. Staphylococcus aureus, Escherichia coli, and Mycoplasma bovis were administered to the groups through intramammary route. Three vaccinated heifers were considered the common control without bacteria in all groups. The parameters considered to assess the effect of vaccination were clinical findings, bacterial count in milk, somatic cell count, and antibody titers. Clinical signs were observed only in the unvaccinated placebo group. Bacteria count and somatic cell count in milk increased in vaccinated and unvaccinated heifers. However, this increase was less in vaccinated animals and gradually returned to the normal level. In the unvaccinated heifers, it was ever high. Serum antibody titers were measured before and after vaccination. Antibody titers were high in vaccinated heifers after vaccination and were negative in unvaccinated heifers. In conclusion, the mixed vaccine had beneficial effect against Staphylococcus aureus, Escherichia coli, and Mycoplasma bovis mastitis and stimulated the immune response of vaccinated heifers.

Rabies is a zoonotic disease with high lethality. Most human deaths are associated with the bites received from dogs and cats. Vaccination is the most effective method of preventing rabies disease in both animals and humans. In this study, the ability of an adjuvant based on recombinant Salmonella typhimurium flagellin to increase protective activity of the inactivated rabies vaccine in mice was evaluated. A series of inactivated dry culture vaccine for dogs and cats "Rabikan" (strain Shchelkovo-51) with addition of an adjuvant at various dilutions were used. The control preparation was a similar series of inactivated dry culture vaccine without an adjuvant. Protective activity of the vaccine preparations was evaluated by the NIH potency test, which is the most widely used and internationally recommended method for testing effectiveness of the inactivated rabies vaccines. The value of specific activity of the tested rabies vaccine when co-administered with the adjuvant was significantly higher (48.69 IU/ml) than that of the vaccine without the adjuvant (3.75 IU/ml). Thus, recombinant flagellin could be considered as an effective adjuvant in the composition of future vaccine preparations against rabies virus.

Background: Over a dozen vaccines are in or have completed phase III trials at an unprecedented speed since the World Health Organization (WHO) declared COVID-19 a pandemic. In this review, we aimed to compare and rank these vaccines indirectly in terms of efficacy and safety using a network meta-analysis., Methods: We searched Embase, MEDLINE, and the Cochrane Library for phase III randomized controlled trials (RCTs) from their inception to September 30, 2023. Two investigators independently selected articles, extracted data, and assessed the risk of bias. Outcomes included efficacy in preventing symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the incidence of serious adverse events (SAEs) according to vaccine type and individual vaccines in adults and elderly individuals. The risk ratio and mean differences were calculated with 95% confidence intervals using a Bayesian network meta-analysis., Results: A total of 25 RCTs involving 22 vaccines were included in the study. None of vaccines had a higher incidence of SAEs than the placebo. Inactivated virus vaccines might be the safest, with a surface under the cumulative ranking curve (SUCRA) value of 0.16. BIV1-CovIran showed the highest safety index (SUCRA value: 0.13), followed by BBV152, Soberana, Gam-COVID-Vac, and ZF2001. There were no significant differences among the various types of vaccines regarding the efficacy in preventing symptomatic SARS-CoV-2 infection, although there was a trend toward higher efficacy of the mRNA vaccines (SUCRA value: 0.09). BNT162b2 showed the highest efficacy (SUCRA value: 0.02) among the individual vaccines, followed by mRNA-1273, Abdala, Gam-COVID-Vac, and NVX-CoV2373. BNT162b2 had the highest efficacy (SUCRA value: 0.08) in the elderly population, whereas CVnCoV, CoVLP + AS03, and CoronaVac were not significantly different from the placebo., Conclusions: None of the different types of vaccines were significantly superior in terms of efficacy, while mRNA vaccines were significantly inferior in safety to other types. BNT162b2 had the highest efficacy in preventing symptomatic SARS-CoV-2 infection in adults and the elderly, whereas BIV1-CovIran had the lowest incidence of SAEs in adults., (© 2024. The Author(s).)

Background: HIV-infected children have a higher risk of presenting infections, including the hepatitis A virus (HAV). The inactivated HAV vaccine is immunogenic in immunocompetent hosts; however, there are insufficient studies on the duration of seroprotection in HIV-infected children., Methods: An analytical cohort study was conducted. HIV-1-infected children who received the inactivated HAV vaccine (2 doses) were included. Blood samples were taken for antibody measurement, the first one 28 days after the second dose and another 7 years after the vaccination schedule. Information on viral load, immunological category, weight, height, and response to antiretroviral treatment from diagnosis to the last assessment was obtained., Results: 19 patients were included, with a mean age of 12.6 years (SD ± 2.29). 58% were male. 80% of the patients presented protective immunoglobulin G antibodies against HAV 7-year post-vaccination. The antibody concentration was found to be between 13 and 80 mIU/mL (median of 80 mIU/mL). 52% showed some degree of immunosuppression. There was no statistically significant relationship between the presence of seroprotection and viral load, treatment failure, immunological category, and malnutrition. Twelve patients presented with antiretroviral treatment failure, and in 33% of them, the antibodies did not offer satisfactory seroprotection., Conclusion: 7-year post-vaccination, 80% of HIV-infected children maintain seroprotection titers against HAV., (Copyright: © 2024 Permanyer.)

Introduction: Inactivated parapoxvirus ovis (iPPVO) exerts strong immunomodulatory effects on innate immune cells, making it an attractive therapeutic candidate. However, little is known about the signaling pathways that are involved in iPPVO-induced immune responses., Methods: In this study, we systematically analyzed how different types of dendritic cells (DCs) react to iPPVO (Zylexis, strain D1701) in both BALB/c and C57BL/6 mice by flow cytometry and ELISAs, and investigated which signaling pathway is related to DC activation by Western blotting and protein profiling., Results: We demonstrated that bone marrow-derived conventional DCs (BM-cDCs) and bone marrow-derived plasmacytoid DCs (BM-pDCs) matured and secreted type I interferons in response to Zylexis stimulation in both mouse strains. Similarly, Zylexis promoted the secretion of IL-12/23p40 and TNF by pDCs. However, IL-12/23p40 and TNF secretion by cDCs were induced in BALB/c mice but not in C57BL/6 mice. Analyzing the underlying signaling pathways revealed that iPPVO-induced maturation of cDCs was Toll-like receptor 9 (TLR9) independent, while the maturation of pDCs partially depended on the TLR9 pathway. Moreover, the production of proinflammatory cytokines by cDCs and the secretion of IFN-α/β by pDCs partially depended on the TLR9 pathway in both mouse strains. Therefore, other signaling pathways seem to participate in the response of DCs to iPPVO, supported by protein profiling., Conclusion: Our data provide useful insights into the diversity of iPPVO sensors and their varying effects across different strains and species., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Influenza viruses can multiply in quails and be transmitted to other animal species. As vaccination reduces virus shedding in chickens, the effect of the killed H9N2 avian influenza virus (AIV) on tissue distribution and virus shedding was evaluated in quails. One hundred 20-day-old quails were divided into six equal groups, kept in separate pens, and fed ad libitum. Before vaccination, blood samples were randomly collected from the wing veins. Four groups were vaccinated with the inactivated H9N2 Razi Institute vaccine at 21 days subcutaneously at the back of neck. Three weeks later, two groups were re-vaccinated. Two weeks later, at the age of 56 days, three groups were challenged with 100 μL of allantoic fluid containing 10 5 EID 50 H9N2 through the oculonasal route. Blood samples were collected from quails at 42, 56, 63, and 70 days from each group to determine AIV antibodies by the hemagglutination inhibition test. Three quails were randomly selected and euthanized from each group on days 1, 3, and 6 post-inoculation (PI). Tissue samples were collected, and the RT-PCR test was performed. No clinical signs or gross lesions existed in any of the groups during the experiment. However, the virus was detected in different tissues on the first, third, and sixth days after the challenge in unvaccinated challenged birds. Virus detection was significantly more frequent in the quails vaccinated once and challenged than in the twice-vaccinated challenged group ( P ≤0.05). On the third day of PI, the virus was detected in some organs of the challenged groups. On the sixth day of PI, the virus was detected only in the lungs of two unvaccinated and once-vaccinated challenged birds. It was concluded that the vaccination of quails against AIV H9 is necessary to protect them from clinical signs, as well as respiratory tract and intestine replication. Two-time vaccination significantly protects the respiratory and intestine tracts, compared to one-time vaccination ( P ≤0.05)., Competing Interests: The authors declare that they have no conflict of interest.

Background: It is important to extend the indication of severe acute respiratory syndrome coronavirus 2 vaccine to children to improve the vaccine intake rate and reduce infection in this population., Methods: In 2 phase 1 and phase 2 randomized, double-blind and placebo-controlled trials, 84 and 480 Chinese healthy children 3 to 17 years old were enrolled, respectively, and randomized in 3:1 ratio to receive 2 doses of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine, KCONVAC or placebo. The 2 doses were given 28 days apart. Adverse events (AEs) were recorded through Day 28 after each dosing. Live virus neutralizing antibody and receptor binding domain antibody (RBD-IgG) were tested before vaccination and after the second dose., Results: Two doses of the vaccine, KCONVAC, elicited geometric mean titers of 142-150 for neutralizing antibody and 4154-4253 for RBD-IgG 28 days after the second dose. Seroconversion rates were 100% after 2 doses for both antibodies in both trials. The predominant AEs were injection-site pain, cough and fever. Most AEs were grade 1 or 2 in intensity. Five participants reported 6 vaccination-unrelated serious AEs in the phase 2 trial., Conclusions: Two doses of this study vaccine, KCONVAC, were well tolerated and immunogenic in children 3 to 17 years of age., Competing Interests: J.L. is an employee of Shenzhen Kangtai Biological Products Co., Ltd. G.L., X.C., Y.L. and W.L. are employees of Beijing Minhai Biotechnology Co., Ltd. The other authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Enterotoxigenic Escherichia coli (ETEC) is an important cause of moderate to severe diarrhoea in children for which there is no licensed vaccine. We evaluated ETVAX®, an oral, inactivated ETEC vaccine containing four E. coli strains over-expressing the major colonization factors CFA/I, CS3, CS5, and CS6, a toxoid (LCTBA) and double mutant heat-labile enterotoxin (dmLT) adjuvant for safety, tolerability, and immunogenicity., Methods: A double-blind, placebo-controlled, age-descending, dose-finding trial was undertaken in 40 adults, 60 children aged 10-23 months, and 146 aged 6-9 months. Adults received one full dose of ETVAX® and children received 3 doses of either 1/4 or 1/8 dose. Safety was evaluated as solicited and unsolicited events for 7 days following vaccination. Immunogenicity was assessed by evaluation of plasma IgA antibody responses to CFA/I, CS3, CS5, CS6, and LTB, and IgG responses to LTB., Results: Solicited adverse events were mostly mild or moderate with only 2 severe fever reports which were unrelated to the vaccine. The most common events were abdominal pain in adults (26.7 % in vaccinees vs 20 % in placebos), and fever in children aged 6-9 months (44 % vs 54  %). Dosage, number of vaccinations and decreasing age had no influence on severity or frequency of adverse events. The vaccine induced plasma IgA and IgG responses against LTB in 100 % of the adults and 80-90 % of the children. In the 6-23 months cohort, IgA responses to more than 3 vaccine antigens after 3 doses determined as ≥2-fold rise was significantly higher for 1/4 dose compared to placebo (56.7 % vs 27.2 %, p = 0.01). In the 6-9 months cohort, responses to the 1/4 dose were significantly higher than 1/8 dose after 3 rather than 2 doses., Conclusion: ETVAX® was safe, tolerable, and immunogenic in Zambian adults and children. The 1/4 dose induced significantly stronger IgA responses and is recommended for evaluation of protection in children., Clinical Trials Registration: The trial is registered with the Pan African Clinical Trials Registry (PACTR Ref. 201905764389804) and a description of this clinical trial is available on: https://pactr.samrc.ac.za/Trial Design., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nils Carlin and Björn Sjöstrand are employees and minority shareholder of Scandinavian Biopharma Holding AB, which holds certain commercial rights to the vaccine tested in this study. Ann-Mari Svennerholm is shareholder of the biotech company Gotovax AB that may receive a small royalty on sales of the ETEC vaccine if it becomes a commercial product. Nils Carlin and Ann-Mari Svennerholm have patent PCT/EP2012/067598-PCT and PCT/EP2011/065784-PCT. All other authors declare that they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Leptospirosis is a neglected disease caused by bacteria of the genus Leptospira and is more prevalent in tropical and subtropical countries. This pathogen infects humans and other animals, responsible for the most widespread zoonosis in the world, estimated to be responsible for 60 000 deaths and 1 million cases per year. To date, commercial vaccines against human leptospirosis are available only in some countries such as Japan, China, Cuba and France. These vaccines prepared with inactivated Leptospira (bacterins) induce a short-term and serovar-specific immune response, with strong adverse side effects. To circumvent these limitations, several research groups are investigating new experimental vaccines in order to ensure that they are safe, efficient, and protect against several pathogenic Leptospira serovars, inducing sterilizing immunity. Most of these protocols use attenuated cultures, preparations after LPS removal, recombinant proteins or DNA from pathogenic Leptospira spp. The aim of this review was to highlight several promising vaccine candidates, considering their immunogenicity, presence in different pathogenic Leptospira serovars, their role in virulence or immune evasion and other factors., (© 2023 The Scandinavian Foundation for Immunology.)

Introduction: China experienced a record surge of coronavirus disease 2019 cases in December 2022, during the pandemic., Methods: We conducted a randomized, parallel-controlled prospective cohort study to evaluate efficacy and antibody duration after a fourth-dose booster with Ad5-nCoV or inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine., Results: A total of 191 participants aged ≥18 years who had completed a three-dose regimen of the inactivated SARS-CoV-2 vaccine 6 months earlier were recruited to receive the intramuscular Ad5-nCoV booster or the inactivated SARS-CoV-2 vaccine. The Ad5-nCoV group had significantly higher antibody levels compared with the inactivated vaccine group at 6 months after the fourth vaccination dose. After the pandemic, the breakthrough infection rate for the Ad5-nCoV and the inactivated vaccine groups was 77.89% and 78.13%, respectively. Survival curve analysis ( p = 0.872) and multivariable logistic regression analysis ( p = 0.956) showed no statistically significant differences in breakthrough infection between the two groups., Discussion: Compared with a homologous fourth dose, a heterologous fourth dose of Ad5-nCoV elicited a higher immunogenic response in healthy adults who had been immunized with three doses of inactivated vaccine. Nevertheless, the efficacy of the two vaccine types was equivalent after the pandemic., Competing Interests: YX and PW are employees of CanSino Biologics and contributed to the conceptualization of the study clinical protocol and electronic case report form design but did not participate in the analysis or interpretation of the data presented in the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Xu, Dai, Zheng, Qin, Wan, Yang, Jiang, Zhang, Hu and Lv.)

Data on the safety and immunity of a heterologous booster (fourth dose) after three-doses of inactivated SARS-CoV-2 vaccine in Chinese adults are limited. We evaluate the safety and immunogenicity of Ad5-nCoV in a randomized, double-blind, parallel-controlled phase 4 clinical trial in Zhejiang, China (NCT05373030). Participants aged 18-80 years (100 per group), administered three doses of inactivated SARS-CoV-2 vaccine ≥6 months earlier, are enrolled and randomized 1:1 into two groups, which are administered intramuscular Ad5-nCoV or inactivated SARS-CoV-2 vaccine (CoronaVac or Covilo). All observed adverse reactions are predictable and manageable. Ad5-nCoV elicits significantly higher RBD-specific IgG levels, with a geometric mean concentration of 2924.0 on day 14 post-booster, 7.8-fold that of the inactivated vaccine. Pseudovirus-neutralizing antibodies to Omicron BA.4/5 show a similar pattern, with geometric mean titers of 228.9 in Ad5-nCoV group and 65.5 in inactivated vaccine group. Ad5-nCoV booster maintains high antibody levels on day 90, with seroconversion of 71.4%, while that of inactivated vaccine is 5.2%, almost pre-booster levels. A fourth Ad5-nCoV vaccination following three-doses of inactivated SARS-CoV-2 vaccine is immunogenic, tolerable, and more efficient than inactivated SARS-CoV-2 vaccine. Ad5-nCoV elicits a stronger humoral response against Omicron BA.4/5 and maintains antibody levels for longer than homologous boosting., (© 2023. Springer Nature Limited.)

Background/aim: To better optimize the inactivated vaccine-induced immune response and improve vaccine protection efficiency, a preliminary study was conducted on the influencing factors of producing neutralizing antibody (NAb) titers against the inactivated coronavirus disease 2019 (COVID-19) vaccine., Materials and Methods: A total of 91 health care volunteers were enrolled from the Immunology Division of the Laboratory Department of Chongqing General Hospital from February to March 2021. The study had a cross-sectional design. All of the volunteers were scheduled to receive a complete dose regimen of the inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine and the vaccination interval between 2 doses was 14 days. Clinical and laboratory features were collected for further analysis., Results: The NAb titers gradually increased after COVID-19 vaccination, and 72.53% (n = 66) of the volunteers had NAbs after the second dose. Eight variables, including CD16 + CD56 + NK cell level before the first dose (HR = 0.94, p = 0.02), CD16 + CD56 + NK cell level after the second dose (HR = 0.94, p = 0.03), interleukin (IL)-2 level before the first dose (HR = 2.09, p = 0.05), mean corpuscular volume (HR = 0.86, p = 0.02), serum urea level (HR = 0.69, p = 0.05), increment of CD19 + B cells (HR = 0.86, p = 0.03), increment of CD4 + /CD8 + T cells (HR = 0.21, p = 0.03), and increment of the IL-6 level (HR = 0.75, p = 0.04) demonstrated a correlation with the NAb titers after COVID-19 vaccination. In the multivariate logistical regression analysis, the serum urea level (HR = 2.32, P = 0.03) and increment of CD19 + B cells (HR = 1.96, p = 0.03) were positively correlated with the NAb titers. The principal component analysis effectively distinguished the response after COVID-19 vaccination. The Pearson correlation analysis indicated that the CD19 + B cell level (r = 0.23, p < 0.001) and IL-2 (r = 0.24, p < 0.001) and IL-6 levels (r = 0.22, p < 0.001) were weakly positively correlated with the concentration of NAbs., Conclusion: The NAbs titers of the inactivated vaccines were positively correlated with the ratio of CD19 + B cell, IL-6, and IL-2 levels in the serum, which provide clinical guidance for inactivated SARS-CoV-2 vaccines., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest., (© TÜBİTAK.)

Respiratory syncytial virus (RSV) infects more than 60% of infants in their first year of life. Since an experimental formalin-inactivated (FI) RSV vaccine tested in the 1960s caused enhanced respiratory disease (ERD), few attempts have been made to vaccinate infants. ERD is characterized by Th2-biased responses, lung inflammation, and poor protective immune memory. Innate immune memory displays an increased nonspecific effector function upon restimulation, a process called trained immunity, or a repressed effector function upon restimulation, a process called tolerance, which participates in host defense and inflammatory disease. Mycobacterium bovis bacillus Calmette-Guérin (BCG) given at birth can induce trained immunity as well as heterologous Th1 responses. We speculate that BCG given at birth followed by FI-RSV may alleviate ERD and enhance protection through promoting trained immunity and balanced Th immune memory. Neonatal mice were given BCG at birth and then vaccinated with FI-RSV+Al(OH) 3 . BCG/FI-RSV+Al(OH) 3 induced trained macrophages, tissue-resident memory T cells (T RM ), and specific cytotoxic T lymphocytes (CTL) in lungs and inhibited Th2 and Th17 cell immune memory, all of which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH) 3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH) 3 prevented the innate tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or T RM in lungs but not memory T cells in spleens. Therefore, BCG given at birth to regulate trained immunity and T RM may be a new strategy for developing safe and effective RSV killed vaccines for young infants. IMPORTANCE RSV is the leading cause of severe lower respiratory tract infection of infants. ERD, characterized by Th2-biased responses, inflammation, and poor immune memory, has been an obstacle to the development of safe and effective killed RSV vaccines. Innate immune memory participates in host defense and inflammatory disease. BCG given at birth can induce trained immunity as well as heterologous Th1 responses. Our results showed that BCG/FI-RSV+Al(OH) 3 induced trained macrophages, T RM , specific CTL, and balanced Th cell immune memory, which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH) 3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH) 3 prevented tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or T RM in lungs but not memory T cells in spleens. BCG at birth as an adjuvant to regulate trained immunity and T RM may be a new strategy for developing safe and effective RSV killed vaccines for young infants.

The purpose of this study is to investigate the production of both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antibodies and autoantibodies in serum following the third booster vaccination of the inactivated COVID-19 vaccine, and to study the effect of B cell subsets with CD27 and CD38 phenotypes in peripheral blood on antibody production. Routine blood indexes, SARS-CoV-2 antibodies, platelet factor 4 and seven antiphospholipid antibodies were detected both before and 2 months after vaccination in the medical staff of the Zhongnan Hospital of Wuhan University. Peripheral blood B cell subtypes were detected before vaccination. Following immunization, the positive rate of anti-N-S1 immunoglobulin (IgG) had increased from 24.8% to 91.3% and the average antibody concentration had increased by 11 times. The positive rate of neutralizing antibody had increased from 24.8% to 91.3%, the average antibody concentration had increased by 12 times, and the primary increased anti-S1 IgG subtype was that of IgG1. Peripheral blood CD27 + CD38+ B cells were positively correlated with antibody levels after vaccination and were a predictor of the antibody response. In addition, although some indicators showed slight absolute changes, the blood parameters and antiphospholipid antibodies of most volunteers were normal both before and after COVID-19 inactivated vaccine inoculation, and there was no statistical difference in abnormal rates either before or after inoculation. Antibodies in vivo were increased after vaccination with the inactivated vaccine, and IgG1 was the main subtype involved in response to the vaccine. Vaccination with the inactivated COVID-19 vaccine did not appear to affect thrombus-related autoantibodies., (© 2022 Wiley Periodicals LLC.)

The recent emergence of COVID-19 variants has necessitated the development of new vaccines that stimulate the formation of high levels of neutralizing antibodies against S antigen variants. A new strategy involves the intradermal administration of heterologous vaccines composed of one or two doses of inactivated vaccine and a booster dose with the mutated S1 protein (K-S). Such vaccines improve the immune efficacy by increasing the neutralizing antibody titers and promoting specific T cell responses against five variants of the RBD protein. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that both administration schedules (i.e. "1 + 1" and "2 + 1") ensured protection against this strain. These results suggest that the aforementioned strategy is effective for protecting against new variants and enhances the anamnestic immune response in the immunized population.

The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera from convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists seven of eight authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.

Objectives: This study aimed to evaluate the safety and immunogenicity of inactivated COVID-19 vaccines in patients with gastrointestinal cancer (GI) cancer. The role of memory B cells (MBCs) in the humoral response to COVID-19 vaccination was also investigated., Methods: In this prospective observational study, GI cancer patients and healthy individuals who had received 2 doses of inactivated COVID-19 vaccines were included. The data regarding adverse effects, serum anti-receptor binding domain (RBD)-IgG, neutralizing antibodies (NAbs), and frequencies of MBCs were collected prospectively., Results: The inactivated COVID-19 vaccines were safe and well tolerated. Serum anti-RBG-IgG and NAbs were lower for cancer patients. Old age, high ASA score, and receiving active chemotherapy were risk factors for lower antibody titers. The frequencies of activated and resting MBCs decreased in (17.45% vs 38.11%, P = 0.002; 16.98% vs 34.13%, P = 0.023), while the frequencies of intermediate and atypical MBCs increased in cancer patients (40.06% vs 19.87%, P = 0.010; 25.47% vs 16.61%, P = 0.025). The serum antibody titer decreased gradually during follow-up but increased when a booster vaccine was given., Conclusion: The inactivated COVID-19 vaccines were well tolerated in patients with GI cancer but with lower immunogenicity. The subpopulations of MBCs were disordered in cancer patients, and a booster vaccine may be prioritized for them., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: It is essential to know about immune response levels after booster doses of the two different types of vaccines, mRNA, and the inactivated, currently used against COVID-19. For this purpose, we aimed to determine the effects of BNT162b2 (BNT) and CoronaVac (CV) boosters on the humoral and cellular immunity of individuals who had two doses of CV vaccination., Methods: The study was conducted in three centers (Koc University Hospital, Istanbul University Cerrahpasa Hospital, and Istanbul University, Istanbul Medical School Hospital) in Istanbul, Turkey. Individuals who had been previously immunized with two doses of CV and no history of COVID-19 were included. The baseline blood samples were collected 3-5 months after the second dose of CV. Follow-up blood samples were taken 1 and 3 months after administration of third doses of CV, or one dose of BNT boosters. Neutralizing antibody titers were measured by plaque reduction assay. The CD4+ T cell, CD8+ T cell, effector CD4+CD38+CD69+ T cell, and effector CD8+CD38+CD69+ T cell ratios were determined by flow cytometry. The intracellular IFN-γ and IL-2 responses were measured by ELISpot assay., Results: We found a 3.38-fold increase in neutralizing antibody geometric mean titers (NA GMT, 78.69) 1 month after BNT booster and maintained at the third month (NA GMT, 80). Nevertheless, in the CV booster group, significantly lower NA GMT than BNT after 1 month and 3 months were observed (21.44 and 28.44, respectively) (p < .001). In the ELISpot assay, IL-2 levels after BNT were higher than baseline and CV booster (p < .001) while IFN-γ levels were significantly higher than baseline (p < .001). The CD8+CD38+CD69+ and CD4+CD38+CD69+ T cells were stimulated predominantly in the third month of the BNT boosters., Conclusion: The neutralizing antibody levels after 3 months of the BNT booster were higher than the antibody levels after CV in fully vaccinated individuals. On the contrary, ratio of the effector T cells increased along with greater IFN-γ activation after BNT booster. By considering the waning immunity, we suggest a new booster dose with BNT for the countries that already had two doses of primary CV regimens., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)