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Abstract Introduction Surveillance programs after hepatitis B surface antigen (HBsAg) loss are not yet well established, and the role of hepatitis B surface antibodies (anti-HBs) remains controversial. We aimed to evaluate the risk factors for increased mortality and the association between anti-HBs and all-cause and cause-specific mortality in a representative US (United States) population of patients with resolved HBV (Hepatitis B virus) infections. Methods Data were taken from the US National Health and Nutrition Examination Survey (NHANES) 1999–2018. A total of 3455 US adults with resolved HBV infection [defined as hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive] were enrolled in this study. The primary outcome measures were all-cause and cause-specific mortality from baseline until 31 December 2019. Results During a mean follow-up of 10.3 years, 741 deaths occurred. Age, race, marital status, smoking status, physical activity level, and presence of cirrhosis, diabetes, cardiovascular diseases, chronic obstructive pulmonary diseases, cancer, and anti-HBs were significant factors for increased mortality, and a nomogram tool was developed and validated for the risk stratification of mortality. Compared with participants who were anti-HBs positive, those who were anti-HBs negative had a 23% (hazard ratio 1.23, 95% CI 1.02–1.46) higher risk of all-cause mortality in NHANES 1999–2018. For cause-specific mortality, the fully adjusted hazard ratios of participants who were anti-HBs negative were 0.71 (95% CI 0.48–1.06) for heart disease, 1.44 (95% CI 1.01–2.05) for cancer, and 1.44 (95% CI 1.13–1.83) for other conditions, compared to those of participants who were anti-HBs positive. Conclusions Among US adults with resolved HBV infections, anti-HBs-negative status was associated with an increased risk of death from all causes and cancer, implying that the role of anti-HBs in resolved HBV infection should not be ignored. On the public health level, more rigorous surveillance was needed for populations of individuals who were isolated anti-HBc positive.

Introduction: Surveillance programs after hepatitis B surface antigen (HBsAg) loss are not yet well established, and the role of hepatitis B surface antibodies (anti-HBs) remains controversial. We aimed to evaluate the risk factors for increased mortality and the association between anti-HBs and all-cause and cause-specific mortality in a representative US (United States) population of patients with resolved HBV (Hepatitis B virus) infections. Methods: Data were taken from the US National Health and Nutrition Examination Survey (NHANES) 1999–2018. A total of 3455 US adults with resolved HBV infection [defined as hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive] were enrolled in this study. The primary outcome measures were all-cause and cause-specific mortality from baseline until 31 December 2019. Results: During a mean follow-up of 10.3 years, 741 deaths occurred. Age, race, marital status, smoking status, physical activity level, and presence of cirrhosis, diabetes, cardiovascular diseases, chronic obstructive pulmonary diseases, cancer, and anti-HBs were significant factors for increased mortality, and a nomogram tool was developed and validated for the risk stratification of mortality. Compared with participants who were anti-HBs positive, those who were anti-HBs negative had a 23% (hazard ratio 1.23, 95% CI 1.02–1.46) higher risk of all-cause mortality in NHANES 1999–2018. For cause-specific mortality, the fully adjusted hazard ratios of participants who were anti-HBs negative were 0.71 (95% CI 0.48–1.06) for heart disease, 1.44 (95% CI 1.01–2.05) for cancer, and 1.44 (95% CI 1.13–1.83) for other conditions, compared to those of participants who were anti-HBs positive. Conclusions: Among US adults with resolved HBV infections, anti-HBs-negative status was associated with an increased risk of death from all causes and cancer, implying that the role of anti-HBs in resolved HBV infection should not be ignored. On the public health level, more rigorous surveillance was needed for populations of individuals who were isolated anti-HBc positive. [ABSTRACT FROM AUTHOR]

Background/Aim. Pregnancy-induced red blood cell (RBC) alloimmunization is important not only because of the possible negative effects on subsequent pregnancy outcomes in case the fetus carries the antigen but also because of the optimal trans-fusion management in cases of obstetric hemorrhage. Timely detection of RBC antibodies is part of testing, prevention, and treatment strategy, aimed at achieving better outcomes for alloimmunized mothers with an affected fetus. The aim of the study was to determine the frequency and specificity of alloantibodies among pregnant women from the South Bačka District, Serbia, with special attention to the incidence of anti-D alloantibodies. Methods. A retrospective study was conducted in the Blood Transfusion Institute of Vojvodina and covered the period from January 1, 2010, to December 31, 2019. Screening and antibody identification were performed by an indirect antiglobulin test in gel-microcards (ID-Card Liss/Coombs) with two test RBC (ID-DiaCell I-II screening cells, Bio-Rad, Cressier, Switzerland) on an automated system (IH-500, Bio-Rad). Results. Among 25,694 tested pregnant women, 1.38% were actively immunized, while 1.12% of women acquired antibodies in the current pregnancy. Among 3,622 (14.09%) RhD-negative women, 1.77% produced anti-D antibodies during the ongoing pregnancy. Distribution of anti-body specificity was: anti-D 23.34%, anti-M 11.85%, anti-E 9.41%, anti-K 9.41%, anti-C 5.92%, anti-Fyb 5.92%, anti-c 3.13%, anti-S 3.13%, anti-Lea 3.13%, anti-Leb 3.13%, anti-Cw 1.75%, anti-Jka 1.40%, anti-P 1.05%, anti-Lub 0.70%, anti-Fya 0.35%, autoantibody of undetermined specificity 0.70%, and irregular antibodies of undetermined specificity 15.68%. Conclusion. Immunoglobulin prophylaxis has led to a significant reduction in the frequency of D-alloimmunization among pregnant women in the South Bačka District over the last ten years. However, the incidence of anti-D antibodies is still significantly higher than in published data for developed countries. We also identified the other, less commonly present, clinically significant antibodies. There is a need to introduce uniform recommendations for immunohematological testing in pregnancy on the territory of the Republic of Serbia in accordance with modern requirements.

In 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) recommended introduction of at least one inactivated poliovirus vaccine (IPV) dose in essential immunization programs. We evaluated systemic humoral and intestinal mucosal immunity of a sequential IPV-bivalent oral poliovirus vaccine (bOPV) schedule compared with a co-administration IPV + bOPV schedule in an open-label, randomized, controlled, non-inferiority, inequality trial in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomized to either: (A) IPV and bOPV at 6 and bOPV at 10 and 14 weeks (IPV + bOPV-bOPV-bOPV); or (B) IPV at 6 and bOPV at 10 and 14 weeks (IPV-bOPV-bOPV). Of 456 participants enrolled and randomly assigned during May-August 2015, 428 (94%) were included in the modified intention-to-treat analysis (arm A: 211, arm B: 217). Humoral immune responses did not differ at 18 weeks between study arms: type 1 (98% versus 96%; p = 0.42), type 2 (37% versus 39%; p = 0.77), and type 3 (97% versus 93%; p = 0.07). Virus shedding one week after the bOPV challenge dose in arm B was non-inferior to arm A (type 1 difference = -3% [90% confidence interval: -6 - 0.4%]; type 3 difference: -3% [-6 to -0.2%]). Twenty-six adverse events including seven serious adverse events were reported among 25 participants including one death; none were attributed to study vaccines. An IPV-bOPV-bOPV sequential schedule induced comparable systemic humoral immunity to all poliovirus types and types 1 and 3 intestinal mucosal immunity as an IPV + bOPV-bOPV-bOPV co-administration schedule., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Khalequ Zaman, Asma Binte Aziz, Mohammad Yunus, Warda Haque b reports financial support was provided by Centers for Disease Control and Prevention. Cynthia J Snider’s spouse previously owned stock in Sanofi Pasteur, (Published by Elsevier Ltd.)

JN.1, the dominating SARS-CoV-2 variant, is antigenically distinct from ancestral BA.1, BA.5 and XBB.1.5 variants, raising concern about effectiveness of updated COVID-19 vaccines. Here, we compared the neutralizing antibody response against JN.1, 1-month after receipt of the three available Moderna mRNA vaccines. Sera obtained from 37, 30 and 30 XBB.1.5, BA.1 and BA.4-5 -vaccine recipients, respectively, were tested for anti-RBD IgG and for JN-1 specific neutralizing antibody levels. Geometric mean fold rise (GMFR) in JN.1 specific neutralizing titers was 27 (95 % CI: 17-43.1), 10.1 (95 % CI: 6.48-15.7) and 8.77 (95 % CI: 5.69-13.5) following XBB.1.5, BA.1 and BA.4-5 vaccines, respectively, translating into a 64 % lower adjusted response (geometric mean ratio [GMR] = 0.36, 95 % CI: 0.21-0.6) in the BA.1 arm, and a 75 % lower response (GMR = 0.25, 95 % CI: 0.15-0.43) in the BA.4-5 arm. This suggests that XBB.1.5 vaccination will most likely, result in improved effectiveness against JN.1 compared with other COVID-19 vaccines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Spyros Chalkias, Rituparna Das and Gamal Elfatarany are employees of Moderna, Inc. and may hold stock/stock options in the company. Gili Regev-Yochay served as a consultant to Merck, GSK, Astrazenca, Pfizer and Moderna., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Heterologous COVID-19 vaccine boosters have not been evaluated for patients with hematological malignancies. A Novavax booster was administered for 56 individuals with hematological malignancies who had received a primary COVID-19 series and prior boosters with mRNA vaccines only. Blood specimens were obtained at baseline (pre-vaccine), 28 days, and 168 days after vaccination with the Novavax booster. The median fold change of anti-Spike IgG was 1.02 (IQR 0.79, 1.3) between baseline and Day 28. Circulating Spike protein-specific B cells increased 1.4-fold at Day 28 (p < 0.05). Increases in antibody and T cell responses were modest without significance, with a waning of humoral and cellular responses at 168 days after vaccination., 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.)

Globally, influenza poses a substantial threat to public health, serving as a major contributor to both morbidity and mortality. The current vaccines for seasonal influenza are not optimal. A novel recombinant hemagglutinin (rHA) protein-based quadrivalent seasonal influenza vaccine, SCVC101, has been developed. SCVC101-S contains standard dose protein (15μg of rHA per virus strain) and an oil-in-water adjuvant, CD-A, which enhances the immunogenicity and cross-protection of the vaccine. Preclinical studies in mice, rats, and rhesus macaques demonstrate that SCVC101-S induces robust humoral and cellular immune responses, surpassing those induced by commercially available vaccines. Notably, a single injection with SCVC101-S can induce a strong immune response in macaques, suggesting the potential for a standard-dose vaccination with a recombinant protein influenza vaccine. Furthermore, SCVC101-S induces cross-protection immune responses against heterologous viral strains, indicating broader protection than current vaccines. In conclusion, SCVC101-S has demonstrated safety and efficacy in preclinical settings and warrants further investigation in human clinical trials. Its potential as a valuable addition to the vaccines against seasonal influenza, particularly for the elderly population, is promising., 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. Authors from Guangdong South China Vaccine Co. Ltd. are current or past employees of this for-profit organization. The authors have submitted patent applications related to the work described herein., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The aim of this study is to investigate the impact of arginine on immune function and postoperative complications in colorectal cancer (CRC) patients., Methods: We conducted a comprehensive search to identify eligible RCTs in various databases, such as PubMed, Cochrane Library, EMBASE, Web of Science, MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP Medicine Information System (VIP), and Chinese Biomedical Database (CBM). This study aimed to examine IgA, IgG, and IgM levels as well as CD4 + and CD8 + counts as well as the CD4 + /CD8 + ratio. Anastomotic leaking, length of stay (LOS), and surgical site infection (SSI) were included as secondary outcomes. Stata (StataCorp, version 14.0) was utilized for data analysis. To ensure the results were reliable, we used meta-regression, sensitivity analysis, and publication bias analysis., Results: A total of 24 publications (including 1883 patients) out of 681 that were retrieved fulfilled the inclusion criteria. The arginine group showed notable improvements in humoral immunity, with gains in IgA (SMD=0.45, 95% CI: 0.30-0.60), IgG (SMD=0.80, 95% CI: 0.64-0.96), and IgM (SMD=0.66, 95% CI: 0.39-0.93). With regards to cellular immunity, the arginine group exhibited a substantial increase in the CD4 + T cell count (SMD = 1.03, 95% CI: 0.67-1.38) compared to the control group. However, the CD4 + /CD8 + ratio decreased significantly (SMD=1.37, 95% CI: 0.88-1.86) in the same arginine group, indicating a change in the balance between these two cell types. Additionally, the CD8 + T cell count showed a notable decrease (SMD=-0.70, 95% CI: -1.09 to -0.32) in the arginine group when compared to the control group. Anastomotic leakage was also considerably lower in the arginine group (SMD=-0.05, 95% CI: -0.08 to -0.02), the rate of SSIs was lower (RR = -0.02, 95% CI: -0.05-0), and the length of time patients spent in the hospital was shorter (SMD=-0.15, 95% CI: -0.38 to -0.08)., Conclusions: After radiation treatment for CRC, arginine improves immune function and decreases the risk of infection problems., Trial Registration: Registration with PROSPERO for this meta-analysis is number CRD42024520509., (© 2024. The Author(s).)

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) in the brain and progressive loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Although the role of neuroinflammation and cellular immunity in PD has been extensively studied, the involvement of humoral immunity mediated by antibodies and B cells has received less attention. This article provides a comprehensive review of the current understanding of humoral immunity in PD. Here, we discuss alterations in B cells in PD, including changes in their number and phenotype. Evidence mostly indicates a decrease in the quantity of B cells in PD, accompanied by a shift in the population from naïve to memory cells. Furthermore, the existence of autoantibodies that target several antigens in PD has been investigated (i.e., anti-α-syn autoantibodies, anti-glial-derived antigen antibodies, anti-Tau antibodies, antineuromelanin antibodies, and antibodies against the renin-angiotensin system). Several autoantibodies are generated in PD, which may either provide protection or have harmful effects on disease progression. Furthermore, we have reviewed studies focusing on the utilization of antibodies as a potential treatment for PD, both in animal and clinical trials. This review sheds light on the intricate interplay between antibodies and the pathological processes in PD, including complement system activation., (© 2024 John Wiley & Sons Ltd.)

Background: This study is aimed at providing information about the timing of booster doses and antibody kinetics in healthcare workers., Methods: This research extends a prospective cohort study conducted at Dokuz Eylul University Hospital in Turkey, covering the period from March 2021 to December 2021. During this timeframe, the antibody levels of the health workers were measured at four different time points. The associations of antibody levels with gender, age, occupation, body mass index (BMI), chronic disease, and smoking were analyzed., Results: There was a significant difference between antibody levels in all four blood draws (p < 0.001). Antibody levels decreased in both those vaccinated with BNT162b2 (p < 0.001) and those vaccinated with CoronaVac (p = 0.002) until the fourth blood draw. There was a significant difference between those vaccinated with one and two doses of booster BNT162b2 before the third blood draw (p < 0.001), which continued at the fourth blood draw (p < 0.001). The antibody levels of those with an interval of 41-50 days between two vaccinations decreased significantly at the fourth blood draw (p < 0.001)., Conclusions: This study provides insight into the dynamics and persistence of antibody response after additional COVID-19 vaccine doses among healthcare workers. The longer the interval between booster doses may result in greater antibody levels being maintained over time, allowing for longer durations of protection., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

This study investigates Cystobasidium benthicum (Cb) probiotic yeast and Cyrtocarpa edulis (Ce) fruit dietary effects, single (0.5 %) or combined (Cb:Ce, 0.25:0.25 %), on growth performance, humoral immunity in serum and skin mucus, and intestinal morphology of Nile tilapia (Oreochromis niloticus) after 14 and 28 days. The Cb group presented the highest (P < 0.05) specific growth rate, weight gain, and absolute growth rate with respect to the control group. Immunological assays indicated that Cb, Ce and Cb:Ce groups increased serum nitric oxide concentration compared to the control group (P < 0.05). Cb and Cb:Ce groups showed the highest serum myeloperoxidase enzyme activity at day 14 and 28, respectively (P < 0.05); whereas, Cb:Ce group had the highest (P < 0.05) myeloperoxidase activity in skin mucus. The superoxide dismutase enzyme activity was unaffected. On day 28, Cb, Ce, and Cb:Ce groups showed higher and lower (P < 0.05) catalase enzyme activity in serum and skin mucus, respectively, compared with the control group. Only the Cb group had higher (P < 0.05) total protein concentration in serum (day 14) and skin mucus (day 14 and 28) with respect to the control group. The lysozyme activity in serum (day 28) and skin mucus (day 14) was higher (P < 0.05) in the Cb group compared to the control group. Only the skin mucus of Ce group showed bactericidal activity against Aeromonas dhakensis (P < 0.05). Histological studies indicated that Cb and Cb:Ce groups increased microvilli height, and Cb, Ce and Cb:Ce augmented goblet cell area at day 14 compared to the control group (P < 0.05). At day 28, microvilli height was higher in all groups and the number of intraepithelial leukocytes increased in Cb and Ce groups with respect to the control group (P < 0.05). The ex vivo assay revealed that A. dhakensis in leukocytes decreased cell viability similar to the control group (P < 0.05). A principal component analysis (PCA) confirmed the results. In conclusion, C. benthicum in the diet was the best supplement to improve the growth and immunity of Nile tilapia., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To understand the changes in humoral immunity and lymphocyte subsets levels among hospitalized children with Mycoplasma pneumoniae (MP) infection from 2019 to 2023., Methods: This study retrospectively analyzed inpatients aged 0-14 years who were diagnosed with MP infection or MP pneumonia in a tertiary hospital from January 2019 to December 2023. The children were divided into three groups: before the implementation of nonpharmaceutical interventions (NPIs), during the implementation of NPIs, and after the NPIs being lifted., Results: A total of 4103 patients were enrolled in this study, of whom 2125 were diagnosed with MP infection and 1978 were diagnosed with MP pneumonia. The number of MP infection cases dramatically decreased early during the implementation of NPIs, and the previous epidemic trend resumed after the NPIs were lifted, with the number of cases during the period 2019-2023 peaked in November 2023. In children aged < 5 years, the levels of IgA and IgM and the percentages of total T cells and cytotoxic T cells in the "before the implementation of NPIs" group were greater than those in the other groups, and the percentage of total B cells was lower than that in the other groups. In children aged ≥ 5 years, the IgM level in the "before the implementation of NPIs" group was greater than that in the other groups., Conclusion: The number of MP-infected hospitalized children decreased significantly after NPI implementation and reached its highest peak during 2019-2023 in November 2023. After the NPIs were lifted, the level of humoral immunity was decreased and balance lymphocyte subsets were disrupted, especially in children aged < 5 years. We should pay close attention to and prevent MP infection in a timely manner after epidemics caused by large respiratory pathogens., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs., Methods: We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses., Results: The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021)., Conclusion: Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objectives: The specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored., Methods: Serum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants., Results: Our data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients., Conclusions: The SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients., 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. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tianxing Ji the behalf of all involved authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, and the early detection and diagnosis of this disease are crucial in reducing mortality rates. The timely diagnosis of LUAD is essential for controlling tumour development and enabling early surgical treatment. GPR56 is a vital G protein-coupled receptor and its role in T lymphocytes has received considerable attention. However, its function in B cells remains unclear. This study aimed to investigate the significance of GPR56 in LUAD. We found that GPR56 exhibited a significant increase in circulating plasmablasts and a decrease in new memory B cells. GPR56 expression in B cells was significantly reduced after LPS stimulation and the proportion of HLA-DR+ and CD40+ proportions were also decreased in GPR56+ B cells after stimulation. Additionally, GPR56 exhibited significant down-regulation in circulating B cell subsets of early-stage LUAD patients, and there were significant correlations between GPR56+ B cell subsets and tumour markers. In conclusion, GPR56 could reflect the hypoactivation state of B cells and the decreased proportion of GPR56+ B cell subset in LUAD patients can signify the active humoral immunity in vivo. The expression of GPR56 in B cells could potentially hold value in the early diagnosis of LUAD., (© 2024 John Wiley & Sons Ltd.)

Immune-priming occurs in insects after a prior pathogen exposure. However, its underlying mechanism in insects remains elusive. In the present work, immune-priming was detected in a lepidopteran insect, Spodoptera exigua. Specifically, a prior infection with a heat-killed pathogenic bacterium, Escherichia coli, led to increased survival upon the second infection of different pathogens. Plasma collected from larvae with the prior infection possessed the immune-priming factor(s) that significantly up-regulated cellular and humoral immune responses of naïve larvae. Our study also finds that variations in the timing of plasma collection for priming larvae resulted in distinct impacts on both cellular and humoral responses. However, when the active plasma exhibiting the immune-priming was heat-treated, it lost this priming activity, therefore suggesting that protein factor(s) play a role in this immune-priming. An immunofluorescence assay showed that the hemocytes collected from the immune-primed larvae highly reacted to a polyclonal antibody specific to a vertebrate lipocalin, apolipoprotein D (ApoD). Among 27 ApoD genes (Se-ApoD1 ∼ Se-ApoD27) of S. exigua, Se-ApoD3 was found to be highly induced during the immune-priming, in which it was shown to be expressed in hemocytes and fat body from a fluorescence in situ hybridization analysis. RNA interference of Se-ApoD3 expression significantly impaired the immune-priming of S. exigua larvae. Moreover, the inhibition of eicosanoid biosynthesis suppressed the immune-priming, in which treatment with a lipoxygenase (LOX) inhibitor-and not treatment with a cyclooxygenase inhibitor-suppressed immune-priming. Further, an addition of LOX product such as lipoxin A 4 or lipoxin B 4 significantly rescued the lost immune-priming activity. Taken together, these results suggest that a complex of ApoD3 and LOX product mediates the immune-priming activity of S. exigua., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals., Methods: We included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (<200/mm 3 and ≥200/mm 3 CD4 cell counts) at 1, 6, and 12 months after primary vaccination., Results: A total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm 3 ) and 1092 controls. At 1 month, after adjustment on age, sex, and BMI, PWH had lower seroneutralization titers than controls, and PWH with <200 CD4 cell/mm 3 had lower anti-Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months postprimary vaccination, we did not observe differences between PWH and controls at 12 months., Conclusion: PWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after 6 months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline., Competing Interests: Declarations of competing interest PL has received payment or honoraria for lectures, presentations, speakers bureau, manuscript writing, or educational events from AstraZeneca, GlaxoSmithKline, Janssen, Moderna, Merck Sharp & Dohme, Pfizer, Sanofi Pasteur, Seqirus. KL has received payment or honoraria for lectures, presentations or educational events from GlaxoSmithKline, Moderna, Merck Sharp & Dohme, Gilead. ZM has received payment or honoraria for lectures and presentations from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer. VP has received honoraria for lectures and presentations from Moderna. OL has received payment or honoraria for lectures, presentations, speakers bureau, or educational events from Sanofi Pasteur; Pfizer, Janssen, Moderna, Merck Sharp & Dohme, Seqirus and grants from Sanofi Pasteur; Pfizer, Janssen, GlaxoSmithKline, Moderna. The other authors declare having no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A diverse antibody repertoire is essential for humoral immunity. Antibody diversification requires the introduction of deoxyuridine (dU) mutations within immunoglobulin genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR). dUs are normally recognized and excised by the base excision repair (BER) protein uracil-DNA glycosylase 2 (UNG2). However, FAM72A downregulates UNG2 permitting dUs to persist and trigger SHM and CSR. How FAM72A promotes UNG2 degradation is unknown. Here, we show that FAM72A recruits a C-terminal to LisH (CTLH) E3 ligase complex to target UNG2 for proteasomal degradation. Deficiency in CTLH complex components result in elevated UNG2 and reduced SHM and CSR. Cryo-EM structural analysis reveals FAM72A directly binds to MKLN1 within the CTLH complex to recruit and ubiquitinate UNG2. Our study further suggests that FAM72A hijacks the CTLH complex to promote mutagenesis in cancer. These findings show that FAM72A is an E3 ligase substrate adaptor critical for humoral immunity and cancer development., (© 2024. The Author(s).)

Background: Currently, there is limited understanding of the specific humoral immune response in BA.5-infected hemodialysis patients (BA.5-CHDPs) with previous COVID-19 vaccination. Additionally, the relevant risk factors for reinfection with XBB variants in BA.5-CHDPs have yet to be elucidated., Method: A total of 178 BA.5-CHDPs were enrolled in this study among 53 patients who had previous vaccination. To compare hemodialysis patients in both unvaccinated and vaccinated for their immune response to the BA.5 subtype infection, we assessed serum levels of anti-ancestral-S1-IgG, anti-BA.5-receptor binding domain (RBD)-IgG, and anti-XBB.1.16-RBD-IgG using enzyme-linked immunosorbent assay, the neutralizing antibody titer against BA.5 and XBB.1.16 was determined using pseudovirus neutralization assays. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with severe infection, the magnitude of specific humoral immunity and susceptibility to XBB variants reinfection., Result: Our findings indicate that BA.5-CHDPs with full or booster vaccinations have higher levels of anti-ancestral-S1-IgG than unvaccinated individuals. However, levels of anti-BA.5-RBD-IgG and anti-XBB.1.16-RBD-IgG are much lower. Booster-vaccinated BA.5-CHDPs have significantly higher levels of BA.5 and XBB.1.16 specific antibodies and neutralizing antibodies than unvaccinated patients. Low globulin levels and shorter hemodialysis duration are independent risk factors for XBB reinfection in BA.5-CHDPs., Conclusion: Although XBB.1.16 specific neutralizing antibody levels were low in BA.5-CHDPs, these levels cannot predict the risk of reinfection; other potential risk factors need to be investigated in the future., 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.)

Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2., Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2 nd dose (Sputnik V or AZD1222) and 3 nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed., Results: Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r 2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population., Discussion: Findings regarding humoral and cellular response are consistent with previous reports., Competing Interests: The authors declare that this study received funding from Novartis and donations from Merck Argentina and Synthon Bagó. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Author Berenice Anabel Silva, as principal investigator, received a 2-year research grant from the Research Council of the Ministry of Health of the Government of the City of Buenos Aires, Argentina., (Copyright © 2024 Silva, Miglietta, Casabona, Wenker, Eizaguirre, Alonso, Casas, Lázaro, Man, Portuondo, Lopez Bisso, Zavala, Casales, Imhoff, Steinberg, López, Carnero Contentti, Deri, Sinay, Hryb, Chiganer, Leguizamon, Tkachuk, Bauer, Ferrandina, Giachello, Henestroza, Garcea, Pascuale, Heitrich, Podhajcer, Vinzón, D’Alotto-Moreno, Benatar, Rabinovich, Pitossi and Ferrari.)

Background: The critical issues of sustained memory immunity following ebolavirus disease among long-term survivors are still unclear., Methods: Here, we examine virus-specific immune and inflammatory responses following in vitro challengd in 12 Sudan virus (SUDV) long-term survivors from Uganda's 2000-2001 Gulu outbreak, 15 years after recovery. Total RNA from isolated SUDV-stimulated and unstimulated peripheral blood mononuclear cells was extracted and analyzed. Matched serum samples were also collected to determine SUDV IgG levels and functionality., Results: We detected persistent humoral (58%, 7 of 12) and cellular (33%, 4 of 12) immune responses in SUDV long-term survivors and identified critical molecular mechanisms of innate and adaptive immunity. Gene expression in immune pathways, the interferon signaling system, antiviral defense response, and activation and regulation of T- and B-cell responses were observed. SUDV long-term survivors also maintained robust virus-specific IgG antibodies capable of polyfunctional responses, including neutralizing and innate Fc effector functions., Conclusions: Data integration identified significant correlations among humoral and cellular immune responses and pinpointed a specific innate and adaptive gene expression signature associated with long-lasting immunity. This could help identify natural and vaccine correlates of protection against ebolavirus disease., Competing Interests: Potential conflicts of interest. All authors: No reported 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) 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.)

Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1-28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose., Competing Interests: Potential conflicts of interest. All authors: No reported 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., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Vaccines targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been pivotal in curtailing the spread of infection. Health care workers, as frontline responders, were among the first to receive vaccination to mitigate coronavirus disease in 2019 (COVID-19) transmission. This study aimed to assess the humoral response elicited by mRNA vaccines, specifically measuring antibodies against the spike S1 protein, a marker of immune response. A cohort of 649 health care workers received three doses of mRNA vaccine, with antibody levels evaluated before and after each dose within a 2- to 3-week interval. Participants were stratified into groups based on prior exposure to the virus: those without prior contact (440 individuals) and those with a history of infection (209 individuals). Among the latter, cases of SARS-CoV-2 infection ranged from asymptomatic (92 individuals) to mild symptomatic (117 individuals). Participants with a history of infection exhibited elevated levels of IgG antibodies against the S1 protein prior to vaccination. Notably, both immunoglobulin IgA class (IgA) and immunoglobulin IgG class (IgG) antibody responses increased significantly post-vaccination, peaking after the second dose for IgG and after the third dose for IgA. Interestingly, the immune response to the vaccine did not vary significantly based on the symptomatic or asymptomatic nature of prior infection. Furthermore, the study findings indicate that completion of the vaccination regimen led to sustained antibody production lasting between 6 months and 9 months. This study underscores the robust and enduring humoral response elicited by mRNA vaccines, particularly among health care workers, irrespective of prior SARS-CoV-2 exposure., (© 2024 Małgorzata Staruszkiewicz et al., published by Sciendo.)

Pentraxin 3 (PTX3), a long pentraxin and a humoral pattern recognition molecule (PRM), has been demonstrated to be protective against Aspergillus fumigatus, an airborne human fungal pathogen. We explored its mode of interaction with A. fumigatus, and the resulting implications in the host immune response. Here, we demonstrate that PTX3 interacts with A. fumigatus in a morphotype-dependent manner: (a) it recognizes germinating conidia through galactosaminogalactan, a surface exposed cell wall polysaccharide of A. fumigatus, (b) in dormant conidia, surface proteins serve as weak PTX3 ligands, and (c) surfactant protein D (SP-D) and the complement proteins C1q and C3b, the other humoral PRMs, enhance the interaction of PTX3 with dormant conidia. SP-D, C3b or C1q opsonized conidia stimulated human primary immune cells to release pro-inflammatory cytokines and chemokines. However, subsequent binding of PTX3 to SP-D, C1q or C3b opsonized conidia significantly decreased the production of pro-inflammatory cytokines/chemokines. PTX3 opsonized germinating conidia also significantly lowered the production of pro-inflammatory cytokines/chemokines while increasing IL-10 (an anti-inflammatory cytokine) released by immune cells when compared to the unopsonized counterpart. Overall, our study demonstrates that PTX3 recognizes A. fumigatus either directly or by interplaying with other humoral PRMs, thereby restraining detrimental inflammation. Moreover, PTX3 levels were significantly higher in the serum of patients with invasive pulmonary aspergillosis (IPA) and COVID-19-associated pulmonary aspergillosis (CAPA), supporting previous observations in IPA patients, and suggesting that it could be a potential panel-biomarker for these pathological conditions caused by A. fumigatus., (© 2024. The Author(s).)

Background: The immune response to coronavirus disease 2019 (COVID-19) vaccination is stronger among adults with prior infection (hybrid immunity). It is important to understand if children demonstrate a similar response to better inform vaccination strategies. Our study investigated the humoral response after BNT162b2 COVID-19 vaccine doses in SARS-CoV-2 naïve and recovered children (5-11 years)., Methods: A multi-institutional, longitudinal, prospective cohort study was conducted. Children were enrolled in a case-ascertained antibody surveillance study in Ottawa, Ontario from September/2020-March/2021; at least one household member was severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive on RT-PCR. In November 2021, BNT162b2 COVID-19 vaccine was authorized for children aged 5-11 in Canada. Children enrolled in the surveillance study intending to receive two vaccine doses were invited to participate in this study from November 2021-April 2022. Main exposure was prior SARS-CoV-2 infection, defined by positive RT-PCR or SARS-CoV-2 anti-N IgG antibody presence. Primary outcome was spike IgG antibody levels measured following the first vaccine dose (2-3 weeks) and second vaccine dose (3-4 weeks)., Results: Of the 153 eligible children, 75 participants (median age 8.9 IQR (7.4, 10.2) years; 38 (50.7 %) female; 59 (78.7 %) Caucasian) had complete follow-up. Fifty-four (72 %) children had prior SARS-COV-2 infection. Spike IgG antibody levels are significantly higher in SARS-CoV-2 recovered participants after receiving the first dose (p < 0.001) and the second (p = 0.01) compared to infection naïve children., Conclusions and Relevance: SARS-CoV-2 recovered children (5-11 years) demonstrated higher antibody levels following first BNT162b2 vaccine dose compared with naïve children. Most reached antibody saturation two to three weeks after the first dose; a second dose didn't change the saturation level. A single vaccine dose in SARS-CoV-2 recovered children may be equivalent or superior to a 2-dose primary series in naïve children. Further research is needed on the durability and quality of a single vaccine dose in this population., Competing Interests: Declaration of competing interest AP reports a relationship with Member of the Task Force for COVID-19 in Children, Government of Canada (no financial compensation) that includes: non-financial support. RZ is supported by a Tier 1 Clinical Research Chair from University of Ottawa., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory., Competing Interests: Declaration of interests Y.W. and H.Q. are co-founders of Emergent Biomed Solutions, Ltd., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Post-COVID-19 condition is recognized as a multifactorial disorder, with persistent presence of viral antigens, discordant immunity, delayed viral clearance, and chronic inflammation. Obesity has emerged as an independent risk factor for both SARS-CoV-2 infection and its subsequent sequelae. In this study, we aimed to predict the molecular mechanisms linking obesity and post-COVID-19 distress. Viral antigen-exposed adipose tissues display remarkable levels of viral receptors, facilitating viral entry, deposition, and chronic release of inflammatory mediators and cells in patients. Subsequently, obesity-associated inflammatory insults are predicted to disturb cellular and humoral immunity by triggering abnormal cell differentiation and lymphocyte exhaustion. In particular, the decline in SARS-CoV-2 antibody titers and T-cell exhaustion due to chronic inflammation may account for delayed virus clearance and persistent activation of inflammatory responses. Taken together, obesity-associated defective immunity is a critical control point of intervention against post-COVID-19 progression, particularly in subjects with chronic metabolic distress., 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 Jang, Hong and Moon.)

Background: A definition of the immunological features of COVID-19 pneumonia is needed to support clinical management of aged patients. In this study, we characterized the humoral and cellular immune responses in presence or absence of SARS-CoV-2 vaccination, in aged patients admitted to the IRCCS San Raffaele Hospital (Italy) for COVID-19 pneumonia between November 2021 and March 2022., Methods: The study was approved by local authorities. Disease severity was evaluated according to WHO guidelines. We tested: (A) anti-SARS-CoV-2 humoral response (anti-RBD-S IgG, anti-S IgM, anti-N IgG, neutralizing activity against Delta, BA1, BA4/5 variants); (B) Lymphocyte B, CD4 and CD8 T-cell phenotype; (C) plasma cytokines. The impact of vaccine administration and different variants on the immunological responses was evaluated using standard linear regression models and Tobit models for censored outcomes adjusted for age, vaccine doses and gender., Result: We studied 47 aged patients (median age 78.41), 22 (47%) female, 33 (70%) older than 70 years (elderly). At hospital admission, 36% were unvaccinated (VAC no ), whilst 63% had received 2 (VAC 2 ) or 3 doses (VAC 3 ) of vaccine. During hospitalization, WHO score > 5 was higher in unvaccinated (14% in VAC 3 vs. 43% in VAC 2 and 44% VACno). Independently from vaccination doses and gender, elderly had overall reduced anti-SARS-CoV-2 humoral response (IgG-RBD-S, p = 0.0075). By linear regression, the anti-RBD-S (p = 0.0060), B (p = 0.0079), CD8 (p = 0.0043) and Th2 cell counts (p = 0.0131) were higher in VAC 2 + 3 compared to VAC no . Delta variant was the most representative in VAC 2 (n = 13/18, 72%), detected in 41% of VAC no , whereas undetected in VAC 3, and anti-RBD-S production was higher in VAC 2 vs. VAC no (p = 0.0001), alongside neutralization against Delta (p = 0141), BA1 (p = 0.0255), BA4/5 (p = 0.0162). Infections with Delta also drove an increase of pro-inflammatory cytokines (IFN-α, p = 0.0463; IL-6, p = 0.0010)., Conclusions: Administration of 3 vaccination doses reduces the severe symptomatology in aged and elderly. Vaccination showed a strong association with anti-SARS-CoV-2 humoral response and an expansion of Th2 T-cells populations, independently of age. Delta variants and number of vaccine doses affected the magnitude of the humoral response against the original SARS-CoV-2 and emerging variants. A systematic surveillance of the emerging variants is paramount to define future vaccination strategies., (© 2024. The Author(s).)

The COVID-19 pandemic highlighted the importance of effective vaccination strategies in controlling the spread of infectious diseases. SARS-CoV-2 vaccine has demonstrated high efficacy in preventing COVID-19 infection in the general population. However, the efficacy of this vaccine in patients with predominantly antibody deficiencies, such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA), should be closely monitored. CVID and XLA are rare genetic disorders that impair the immune system's ability to produce antibodies, which are crucial for fighting infections. Patients with these disorders have a higher risk of severe disease and mortality from COVID-19 due to their compromised immune systems. In this study, we evaluated the humoral and cellular immune responses after four doses of mRNA-1273 and one BNT162b2 bivalent vaccine in a cohort of patients with CVID and XLA. The response in this population was lower than in the control group. However, the administration of the third dose improved the number of patients with seroconversion and the intensity of the humoral response, as well as the number of patients with a positive cellular response. Finally, the administration of the fourth and fifth doses improves the antibody titer and neutralization against wild type variant, but not against the prevalent XBB1.5 variant., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. 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.)

Humoral immunity is a major waypoint towards chronic allograft dysfunction in lung transplantation (LT) recipients. Though allo-immunization and antibody-mediated rejection (AMR) are well-known entities, some diagnostic gaps need to be addressed. Morphological analysis could be enhanced by digital pathology and artificial intelligence-based companion tools. Graft transcriptomics can help to identify graft failure phenotypes or endotypes. Donor-derived cell free DNA is being evaluated for graft-loss risk stratification and tailored surveillance. Preventative therapies should be tailored according to risk. The donor pool can be enlarged for candidates with HLA sensitization, with strategies combining plasma exchange, intravenous immunoglobulin and immune cell depletion, or with emerging or innovative therapies such as imlifidase or immunoadsorption. In cases of insufficient pre-transplant desensitization, the effects of antibodies on the allograft can be prevented by targeting the complement cascade, although evidence for this strategy in LT is limited. In LT recipients with a humoral response, strategies are combined, including depletion of immune cells (plasmapheresis or immunoadsorption), inhibition of immune pathways, or modulation of the inflammatory cascade, which can be achieved with photopheresis. Altogether, these innovative techniques offer promising perspectives for LT recipients and shape the 21st century's armamentarium against AMR., 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 Messika, Belousova, Parquin and Roux.)

Since Porcine Circovirus 3 (PCV3) was first identified in 2016, our understanding of the humoral response is still relatively scarce. Current knowledge of the PCV3 humoral response is primarily based on field studies identifying the seroprevalence of PCV3 Cap-induced antibodies. Studies on the humoral response following experimental PCV3 infection have conflicting results where one study reports the development of the Cap IgG response 7 days postinfection with no concurrent Cap IgM response, while a second study shows a Cap IgM response at the same time point with no detection of Cap IgG. The dynamics of the PCV3 Cap and Rep IgG following maternal antibody transfer and experimental infection have not been well characterized. Additionally, the cross-reactivity of convalescent serum from PCV2 and PCV3 experimentally infected animals to serologic methods of the alternate PCV has limited evaluation. Here, we show that maternally derived antibodies were detectable in piglet serum 7-9 weeks postfarrowing for the Cap IgG and 5-weeks-post farrowing for the Rep IgG using Cap- and Rep-specific enzyme linked immunosorbent assays (ELISA) and immunofluorescent assays (IFA) methods. Following experimental inoculation, Cap IgG was detected at 2-weeks-post inoculation and Rep IgG detection was delayed until 4-weeks-post inoculation. Furthermore, convalescent serum from either PCV2 or PCV3 methods displayed no cross-reactivity by serological methods against the other PCV. The information gained in this study highlights the development of both the Cap- and Rep-specific antibodies following experimental infection and through the transfer of maternal antibodies. The increased understanding of the dynamics of maternal antibody transfer and development of the humoral response following infection gained in the present study may aid in the establishment of husbandry practices and potential application of prophylactics to control PCV3 clinical disease., Importance: Research on Porcine Circovirus 3 (PCV3) immunology is vital for understanding and controlling this virus. Previous studies primarily relied on field observations, but they have shown conflicting results about the immunological response against PCV3. This study helps fill those gaps by looking at how antibodies develop in pigs, especially those maternal-derived, and their impact in neonatal pigs preventing PCV3-associated disease in piglets. In addition, we look at the dynamics of antibodies in experimental infections mimicking infection in pigs in the grower-phase condition. Understanding this process can help to develop better strategies to prevent PCV3 infection. Also, this research found that PCV2 and PCV3 do not cross-react, which is crucial for serological test development and results interpretation. Overall, this work is essential for improving swine health and farming practices in the face of PCV3 infections., Competing Interests: The authors declare no conflict of interest.

Bats harbor viruses that can cause severe disease and death in humans including filoviruses (e.g., Ebola virus), henipaviruses (e.g., Hendra virus), and coronaviruses (e.g., SARS-CoV). Bats often tolerate these viruses without noticeable adverse immunological effects or succumbing to disease. Previous studies have largely focused on the role of the bat's innate immune response to control viral pathogenesis, but little is known about bat adaptive immunity. A key component of adaptive immunity is the humoral response, comprised of antibodies that can specifically recognize viral antigens with high affinity. The antibody genes within the 1,400 known bat species are highly diverse, and these genetic differences help shape fundamental aspects of the antibody repertoire, including starting diversity and viral antigen recognition. Whether antibodies in bats protect, mediate viral clearance, and prevent transmission within bat populations is poorly defined. Furthermore, it is unclear how neutralizing activity and Fc-mediated effector functions contribute to bat immunity. Although bats have canonical Fc genes (e.g., mu, gamma, alpha, and epsilon), the copy number and sequences of their Fc genes differ from those of humans and mice. The function of bat antibodies targeting viral antigens has been speculated based on sequencing data and polyclonal sera, but functional and biochemical data of monoclonal antibodies are lacking. In this review, we summarize current knowledge of bat humoral immunity, including variation between species, their potential protective role(s) against viral transmission and replication, and address how these antibodies may contribute to population dynamics within bats communities. A deeper understanding of bat adaptive immunity will provide insight into immune control of transmission and replication for emerging viruses with the potential for zoonotic spillover., 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 Roffler, Maurer, Lunn, Sironen, Forbes and Schmidt.)

The immune and sensory nervous systems communicate to maintain homeostasis. Wu et al. recently demonstrated that sensory neurons innervate the mouse spleen. These neurons promote calcitonin gene-related peptide (CGRP)-dependent responses in splenic B cell germinal centers (GCs) and antigen-specific antibody production. Dietary capsaicin activates these neurons to enhance humoral immunity against influenza virus infection., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Xenotransplantation using pig organs is now a clinical reality. However, the process for xenograft recipient screening lacks clarity and scientific rigor: no established thresholds exist to determine which levels of preformed antipig natural antibodies (Nabs) will be safe for clinical xenograft transplantation, and hyperacute rejection (HAR) or acute humoral xenograft rejection (AHXR), which still impacts pig-to-primate kidney xenograft survivals, may impede broader application of pig-to-human clinical xenograft transplantation., Methods: We retrospectively examined 28 cases of pig-to-baboon kidney xenotransplantation using GalTKO±human complement regulatory protein (hCRP)-transgenic (Tg) pig donors, as well as 6 cases of triple-KO multi-Tg (10GE) pig donors, and developed screening algorithms to predict risk of HAR/AHXR based on recipient antipig Nab levels. Preformed Nabs were evaluated using both complement-dependent cytotoxicity and antibody (IgM and IgG) binding flow-cytometry assays., Results: High complement-dependent cytotoxicity was associated with HAR/AHXR as expected. However, we also found that high levels of IgG were independently associated with HAR/AHXR, and we developed 2 indices to interpret and predict the risk of IgG-mediated HAR/AHXR., Conclusions: Based on the data in this study, we have established a new 2-step screening, which will be used for future clinical kidney xenotransplantation trials., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors that play a critical role in the immune response of invertebrates and vertebrates. Herein, the short ApPGRP-D gene was cloned from the model lepidopteran Antheraea pernyi. Quantitative PCR (qPCR) confirmed that ApPGRP-D is an immune-related protein and that the expression of ApPGRP-D can be induced by microorganisms. ApPGRP-D is a broad-spectrum pattern recognition protein that activates the prophenoloxidase cascade activation system and promotes the agglutination of microbial cells. Likely due to its amidase activity, ApPGRP-D can inhibit the growth of E. coli and S. aureus. In addition, we demonstrated for the first time that zinc ions, as important metal coenzymes, could promote multiple functions of ApPGRP-D but not its amidase activity., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Long COVID (LC) is characterized by persistent symptoms following SARS-CoV-2 infection, with various mechanisms offered to explain its pathogenesis. This study explored whether adaptive humoral anti-SARS-CoV-2 responses differ in LC. Unvaccinated COVID-19 convalescents (n = 200) were enrolled, with 21.5% (n = 43) presenting LC three months post-infection. LC diagnosis was based on persistent symptom(s) and alterations in biochemical/clinical markers; three phenotypes were distinguished: cardiological, pulmonary, and psychiatric LC. All three phenotypes were characterized by significantly decreased seroprevalence of IgG antibodies against nucleocapsid (anti-NP). LC was associated with decreased odds of testing positive for anti-NP (OR = 0.35, 95%CI: 0.16-0.78, p = 0.001). Seropositive LC patients had lower anti-S1 and anti-S2 levels than individuals without LC, and those with pulmonary and psychological phenotypes also revealed decreased anti-RBD concentrations. The results indicate that LC can be characterized by diminished humoral response to SARS-CoV-2. The potential implication of this phenomenon in post-acute viral sequelae is discussed., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

We conducted a cross-sectional study to evaluate cellular and humoral immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection and examine how lymphocyte subpopulations in peripheral blood correlate with cellular and humoral immunogenicity in adult allogeneic hematopoietic cell transplantation (HCT) recipients. The median period from SARS-CoV-2 vaccination or infection to sample collection was 110.5 days (range, 6-345 days). The median SARS-CoV-2 spike-specific antibody level was 1761 binding antibody units (BAU)/ml (range, 0 to > 11,360 BAU/ml). Enzyme-linked immunosorbent spot (ELISpot) assay of T cells stimulated with SARS-CoV-2 spike antigens showed that interferon-gamma (IFN-γ)-, interleukin-2 (IL-2)-, and IFN-γ + IL-2-producing T cells were present in 68.9%, 62.0%, and 56.8% of patients, respectively. The antibody level was significantly correlated with frequency of IL-2-producing T cells (P = 0.001) and IFN-γ + IL-2-producing T cells (P = 0.006) but not IFN-γ-producing T cells (P = 0.970). Absolute counts of CD8+ and CD4+ central memory T cells were higher in both IL-2- and IFN-γ + IL-2-producing cellular responders compared with non-responders. These data suggest that cellular and humoral immunogenicity against SARS-CoV-2 vaccination or infection is associated with the memory phenotype of T cells and B cells in adult allogeneic HCT recipients., (© 2024. The Author(s).)

Poxviruses gained international attention due to the sharp rise in monkeypox cases in recent years, highlighting the urgent need for the development of a secure and reliable vaccine. This study involved the development of an innovative combined subunit vaccine (CSV) targeting poxviruses, with lumpy skin disease virus (LSDV) serving as the model virus. To this end, the potential sites for poxvirus vaccines were fully evaluated to develop and purify four recombinant proteins. These proteins were then successfully delivered to the dermis in a mouse model by utilizing dissolvable microneedle patches (DMPs). This approach simplified the vaccination procedure and significantly mitigated the associated risk. CSV-loaded DMPs contained four recombinant proteins and a novel adjuvant, CpG, which allowed DMPs to elicit the same intensity of humoral and cellular immunity as subcutaneous injection. Following immunization with SC and DMP, the mice exhibited notable levels of neutralizing antibodies, albeit at a low concentration. It is noteworthy that the CSV loaded into DMPs remained stable for at least 4 months at room temperature, effectively addressing the storage and transportation challenges. Based on the study findings, CSV-loaded DMPs are expected to be utilized worldwide as an innovative technique for poxvirus inoculation, especially in underdeveloped regions. This novel strategy is crucial for the development of future poxvirus 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.)

Purpose: In contrast to adults, immune protection against SARS-CoV-2 in children and adolescents with natural or hybrid immunity is still poorly understood. The aim of this study was to analyze different immune compartments in different age groups and whether humoral immune reactions correlate with a cellular immune response., Methods: 72 children and adolescents with a preceding SARS-CoV-2 infection were recruited. 37 were vaccinated with an RNA vaccine (BNT162b2). Humoral immunity was analyzed 3-26 months (median 10 months) after infection by measuring Spike protein (S), nucleocapsid (NCP), and neutralizing antibodies (nAB). Cellular immunity was analyzed using a SARS-CoV-2-specific interferon-γ release assay (IGRA)., Results: All children and adolescents had S antibodies; titers were higher in those with hybrid immunity (14,900 BAU/ml vs. 2118 BAU/ml). NCP antibodies were detectable in > 90%. Neutralizing antibodies (nAB) were more frequently detected (90%) with higher titers (1914 RLU) in adolescents with hybrid immunity than in children with natural immunity (62.5%, 476 RLU). Children with natural immunity were less likely to have reactive IGRAs (43.8%) than adolescents with hybrid immunity (85%). The amount of interferon-γ released by T cells was comparable in natural and hybrid immunity., Conclusion: Spike antibodies are the most reliable markers to monitor an immune reaction against SARS-CoV-2. High antibody titers of spike antibodies and nAB correlated with cellular immunity, a phenomenon found only in adolescents with hybrid immunity. Hybrid immunity is associated with markedly higher antibody titers and a higher probability of a cellular immune response than a natural immunity., (© 2024. The Author(s).)

Objective: Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2 protecting individuals, especially the immunocompromised, from COVID-19. Still, it remains largely unknown how solid organ transplant and different immunosuppressive medications affect development of vaccine-induced immunity., Methods: In this work, we monitored humoral and cellular memory responses after mRNA SARS-CoV-2 two-doses and booster doses vaccination in cystic fibrosis lung transplanted patients (CFT) and compared them with both cystic fibrosis patients without lung transplant (CF) and with kidney transplant recipients (KT). In particular, we investigated the effects of immunosuppressive regimens on immune memory to SARS-CoV-2 after mRNA SARS-CoV-2 vaccine in transplanted patients., Results: Our results showed that immunocompromised transplanted patients displayed a weak cellular and humoral memory to SARS-CoV-2 mRNA vaccination. In addition, obtained data clearly demonstrate that immunosuppressive therapy regimen including antimetabolites, further reduces patients' ability to respond to vaccination at both humoral and cell-mediated level. Notably, patient treated with antimetabolites showed a lower humoral and cellular response also after a booster dose vaccination., Conclusion: These results, even if obtained on a small patient's cohort, question whether immunocompromised patients need interventions to improve vaccine SARS-CoV-2 mRNA vaccine response such as additional jab or modulation of immunosuppressive therapy., Competing Interests: Declaration of competing interest Regarding the submission of our manuscript entitled “Effect of antimetabolite regimen on cellular and humoral immune response to SARS-COV-2 vaccination in solid organ transplant recipients”, I'm writing to confirm that the authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: A BCG booster vaccination administered via the respiratory mucosa may establish protective immune responses at the primary site of Mycobacterium tuberculosis infection. The primary objective of this trial was to compare the safety and immunogenicity of inhaled versus intramuscular administered ChAdOx1-85A., Methods: We conducted a single-centre, randomised, double-blind, controlled phase 1 study (Swiss National Clinical Trials Portal number SNCTP000002920). After a dose-escalation vaccination in nine BCG-vaccinated healthy adults, a dose of 1 × 10 10 vp of ChAdOx1-85A was administered to twenty BCG-vaccinated adults that were randomly allocated (1:1) into two groups: aerosol ChAdOx1-85A with intramuscular saline placebo or intramuscular ChAdOx1-85A with aerosol saline placebo, using block randomisation. A control group of ten BCG-naïve adults received aerosol ChAdOx1-85A at the same dose. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 16 post-vaccination and Serious AEs (SAEs) up to 24 weeks; secondary outcomes were cell-mediated and humoral immune responses in blood and bronchoalveolar lavage (BAL) samples., Findings: Both vaccination routes were well tolerated with no SAEs. Intramuscular ChAdOx1-85A was associated with more local AEs (mostly pain at the injection site) than aerosol ChAdOx1-85A. Systemic AEs occurred in all groups, mainly fatigue and headaches, without differences between groups. Respiratory AEs were not different between BCG-vaccinated groups. Aerosol ChAdOx1-85A vaccination induced Ag85A BAL and systemic cellular immune responses with compartmentalisation of the immune responses: aerosol ChAdOx1-85A induced stronger BAL cellular responses, particularly IFNγ/IL17+CD4+ T cells; intramuscular ChAdOx1-85A induced stronger systemic cellular and humoral responses., Interpretation: Inhaled ChAdOx1-85A was well-tolerated and induced lung mucosal and systemic Ag85A-specific T-cell responses. These data support further evaluation of aerosol ChAdOx1-85A and other viral vectors as a BCG-booster vaccination strategy., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Bacterial septicemia in freshwater fish is mainly caused by Aeromonas hydrophila infection, which affects the development of aquaculture industry. In the context of sustainable aquaculture, subunit vaccines are of great values because they play positive roles in reducing the overuse of antibiotics and protecting aquatic animals against bacterial infection. In this study, the recombinant outer membrane protein OmpTS of A. hydrophila were used as subunit vaccine to immunize Megalobrama amblycephala, and its immunoprotective effect and host immune responses were evaluated. The survival rates of the vaccinated groups after bacterial infection were significantly higher than that of the control group, especially of the OmpTS high-dose vaccinated group. The better protective effects of vaccinated groups might be attributed to the increased levels of serum IgM-specific antibody titer, the reduced relative abundance of A. hydrophila in various tissues, the increased number of immune-positive cells with different epitopes, the up-regulated expression levels of immune-related genes, and the enhanced activities of antibacterial enzymes. In conclusion, OmpTS subunit vaccine could strongly induce host immune responses in M. amblycephala, thereby enhancing both cellular and humoral immunity, which exhibited excellent and effective immunoprotective efficacy., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Streptococcus suis is one of the major pathogens of pigs circulating worldwide, and the development of vaccines will help to effectively control streptococcosis in swine. In this study, we evaluated the potential of three membrane associated proteins, histidine kinase (HK), glycosyltransferase family 2 (Gtf-2) and phosphate binding protein (PsbP) of S. suis as subunit vaccines. Bioinformatics analysis shows that protein ABC is highly conserved in S. suis. To verify the protective effects of these proteins in animal models, recombinant protein HK, Gtf-2 and PsbP were used to immunize BALB/c mice separately. The results showed that these proteins immunization in mice can effectively induce strong humoral immune responses, protect mice from cytokine storms caused by S. suis infection, and have a significant protective effect against lethal doses of S. suis infection. Furthermore, antibodies with opsonic activity exist in the recombinant proteins antiserum to assist phagocytic cells in killing S. suis. Overall, these results indicated that these recombinant proteins all elicit good immune protective effect against S. suis infection and can be represent promising candidate antigens for subunit vaccines against S. suis., Competing Interests: Declaration of competing interest The Authors declare no Competing Financial or Non-Financial Interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The humoral immune system comprises B cells and plasma cells, which play important roles in organ transplantation, ranging from the production of both protective and injurious antibodies as well as cytokines that can promote operational tolerance. Recent data from conditions outside of transplantation have identified a novel human B-cell subset that expresses the transcription factor T-bet and exerts pleiotropic functions by disease state. Here, we review the generation, activation, and functions of the T-bet + B-cell subset outside of allotransplantation, and consider the relevance of this subset as mediators of allograft injury., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Pasteurella multocida is affecting a multitude of animals and severely affects livestock production. Existing vaccines are mostly chemically inactivated and do not lead to wide protection. Irradiated vaccines are enjoying a renaissance and the concept of "replication defficient but metabolically active" vaccines was recently evaluated in several vaccine trials. P. multocida was isolated from the nasal swab, blood, and lung swab samples from infected rabbits. Gamma irradiation of P. multocida for inhibition of replication was evaluated at an optimized irradiation dose of 10 Kgy established. Four groups of rabbits were (mock) vaccinated with a commercial P. multocida vaccine and three irradiated formulations as liquid, lyophilized formulations with added Trehalose and lyophilized-Trehalose with an "activation" culturing the irradiated bacteria for 24 in broth. Evaluation of humoral immune response by ELISA showed that all three irradiated vaccines produced an effective, protective, and continued IgG serum level after vaccination and bacterial challenge. The IFN-γ expression is maintained at a normal level, within each individual group however, the lyophilized trehalose irradiated vaccine showed peak mean of IFN-γ titer at one week after booster dose (day 21) which was statistically significant. Cumulatively, the results of this study show that gamma-irradiated P. multocida vaccines are safe and protect rabbits against disease. Moreover, Rabbits' immunization with the three irradiated formulations avoided adverse side effects as compared to commercial polyvalent vaccine, the body weight gain for the irradiated vaccine groups indicates less stress compared to the commercial polyvalent vaccine., (© 2024. The Author(s).)

Basic leucine zipper domain transcription factors (TFs), of which yeast activator protein (Yap) is a significant class, are crucial for the development of sclerotia, the stress response, vegetative growth, and spore adhesion. Nevertheless, nothing is known about how Yap TFs contribute to the pathogenicity of entomopathogenic fungus. In this work, Beauveria bassiana was used to identify and knock out the yeast gene BbYap1 , which is similar to Yap. The BbYap1 gene deletion has an impact on lipid homeostasis of B. bassiana ; oleic acid, for example, dropped by 95.69%. The BbYap1 mutant exhibited much less virulence and vegetative development in comparison to the wild strain, while demonstrating a greater sensitivity to chemical stress. It is noteworthy that the physiological abnormalities brought on by BbYap1 deletion were largely repaired by the addition of exogenous oleic acid, as seen by the notable increase in insect survival in the blood cavity injection group. Following infection with the BbYap1 mutant, the host exhibits a considerable down-regulation of the expression of β-1,3-glucan recognition protein, gallerimycin, gloverin, and moricin-like protein genes. Likewise, the introduction of exogenous oleic acid markedly increased the host's expression of the aforementioned genes. In summary, BbYap1 regulates cellular enzyme lipid homeostasis and fungal virulence by eluding host humoral defense, which contributes to fungal chemical stress and vegetative development., Importance: Entomopathogenic fungi (EPF) offer an effective and eco-friendly alternative to curb insect populations in biocontrol strategy. When EPF enter the hemolymph of their host, they encounter a variety of stress reactions, such as immunological and oxidative stress. Basic leucine zipper domain transcription factors, of which yeast activator protein (Yap) is a significant class, have diverse biological functions related to metabolism, development, reproduction, conidiation, stress responses, and pathogenicity. This study demonstrates that BbYap1 of Beauveria bassiana regulates cellular enzyme lipid homeostasis and fungal virulence by eluding host humoral defense, which contributes to fungal chemical stress and vegetative development. These findings offer fresh perspectives for comprehending molecular roles of YAP in EPF., Competing Interests: The authors declare no conflict of interest.

The SARS-CoV-2 outbreak has provoked more than 6 million deaths worldwide. The scarcity of effective treatments and its virulence converted the vaccines into an essential tool to face it. The most used vaccines were the mRNA, adenovirus vector, and inactivated whole-virus. However, nowadays, infants aged < 6 months are not eligible for any vaccines against COVID-19, and their immunization relies on passive immunity. In this research, we investigated the humoral and cellular immune response generated on newborns of SARS-CoV-2 vaccinated mothers with mRNA or viral vector (VV) vaccine employing Fourier transformed infrared (FTIR) spectroscopy in saliva samples. For this purpose, saliva samples of newborns and their mothers were collected; the population was divided into two groups, VV and mRNA, which were subdivided into three subgroups: before pregnancy (BP), at the first (FTP) and second (STP) trimesters of pregnancy. The samples were analyzed using FTIR spectroscopy, and the bands associated with the humoral and cellular immune responses, such as IgG, IgA, and IFN-γ were analyzed. The integrated areas were calculated and compared to elucidate the quantity of those immunoglobins and the cytokine. Likewise, the correlation of the humoral and cellular immune response between the newborns and their mothers and the correlation between cellular and humoral immune response was also evaluated. The VV vaccine produced a significant humoral and cellular immune response in newborns and their mothers when they received it at the STP compared with the mRNA vaccine, evidencing statistical significance. However, no correlation was observed between newborns and their mothers when the vaccine was applied in this trimester of pregnancy. When administered BP, the mRNA vaccine generated more humoral immunity in newborns and their mothers. Nevertheless, compared with the VV vaccine, it only showed statistical significance in the mothers, highlighting that IgG showed a moderate positive correlation between the newborns and their mothers., (© 2024. The Author(s).)

With the rapid global spread of COVID-19 and the continuous emergence of variants, there is an urgent need to develop safe and effective vaccines. Here, we developed a novel mRNA vaccine, HC009, based on new formulation by the QTsome delivery platform. Immunogenicity results showed that the prime-boost immunization strategy with HC009 was able to induce robust and durable humoral immunity, as well as Th1-biased cellular responses in rodents or non-human primates (NHPs). After further challenge with live SARS-CoV-2 virus, HC009 provided adequate protection against virus infection in hACE2 transgenic mice. Therefore, HC009 could provide significant immune protection against SARS-CoV-2., Competing Interests: All authors were employed by the company Zhejiang Haichang Biotech Co., Ltd., (Copyright © 2024 Liu, Han, Yang, Zhang, Li, Chen, Wu, Zhao and Yang.)

Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have contributed to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMVs) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant MCMV vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMV S ). In this study, we show that the MCMV S elicits a robust and lasting protection in young and aged mice. Notably, spike-specific humoral and cellular immunity was not only maintained but also even increased over a period of at least 6 months. During that time, antibody avidity continuously increased and expanded in breadth, resulting in neutralization of genetically distant variants, like Omicron BA.1. A single dose of MCMV S conferred rapid virus clearance upon challenge. Moreover, MCMV S vaccination controlled two variants of concern (VOCs), the Beta (B.1.135) and the Omicron (BA.1) variants. Thus, CMV vectors provide unique advantages over other vaccine technologies, eliciting broadly reactive and long-lasting immune responses against COVID-19., Competing Interests: LČ-Š, SJ, and YK are applicants for a patent based on MCMV as a vaccine vector. LČ-Š served as advisor to SANOFI for COVID vaccines, unrelated to this study. 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Metzdorf, Jacobsen, Kim, Teixeira Alves, Kulkarni, Brdovčak, Materljan, Eschke, Chaudhry, Hoffmann, Bertoglio, Ruschig, Hust, Šustić, Krmpotić, Jonjić, Widera, Ciesek, Pöhlmann, Landthaler and Čičin-Šain.)