Search

The common cold coronaviruses are a source of ongoing morbidity and mortality particularly among elderly and immunocompromised individuals. While cross-reactive immune responses against multiple coronaviruses have been described following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, it remains unclear if these confer any degree of cross-protection against the common cold coronaviruses. A recombinant fowl adenovirus vaccine expressing the SARS-CoV-2 spike protein (FAdV-9-S19) was generated, and protection from SARS-CoV-2 challenge was shown in K18-hACE2 mice. Vaccinated mice were also challenged with the common cold coronaviruses human coronavirus (HCoV)-OC43 and HCoV-NL63 by the intranasal route, and viral shedding and lung burden were reduced in these groups compared to unvaccinated animals. Histopathological analysis of lung tissues revealed significantly less inflammation and lower pathology scores in mice that received FAdV-9-S19 . Because no mouse model for the coronavirus HCoV-229E exists, we vaccinated and challenged cynomolgus macaques to evaluate cross-protection against HCoV-229E. Animals were monitored for clinical signs of disease and viral shedding. Infectious virus was detected in both groups throughout the course of infection; however, vaccinated animals showed reduced viral shedding at multiple time points after infection. Histopathological analysis of lung tissues following challenge also indicated a more moderate disease in the vaccinated animals. Therefore, vaccination with FAdV-9-S19 also provided a moderate cross-protection against HCoV-229E disease in the cynomolgus macaques infection model. Our study demonstrates that vaccination with a recombinant fowl adenovirus expressing SARS-CoV-2 spike protein can provide a low-level cross-protection against beta- and alphacoronaviruses. These findings are important for the design of future pan-coronavirus vaccines.IMPORTANCEThe common cold coronaviruses are a source of ongoing morbidity and mortality particularly among elderly and immunocompromised individuals, and no vaccine is currently available. Cross-reactive immune responses have been described following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination; however, it remains unclear what degree of cross-protection they confer against the common cold coronaviruses. We demonstrate that both humoral and cell-mediated immune responses provide a low-level cross-protection, resulting in reduced viral load and pathology for the common cold coronaviruses OC43 and NL63 in mouse models. Additionally, we present a novel non-human primate (NHP) model of infection with the common cold coronavirus 229E, demonstrating that it mimics the disease observed in humans and can serve as a model for future vaccine studies, as cross-protection was also observed. This is significant as it suggests that current vaccines could provide a low-level protection against other coronaviruses and could serve as part of vaccination strategy against future novel coronaviruses., Competing Interests: The authors declare no conflict of interest.

To investigate the immunogenic cross-reactivity among different novel duck reovirus isolates, animals immunized with monovalent inactivated duck reovirus were challenged with homologous and heterologous viruses, and serum samples were collected after immunization for cross-neutralization test. The results showed that the virus neutralizing titer against homologous virus was significantly higher than that against heterologous virus(p < 0.000001), which indicated that there was an important difference in antigenicity between DE13 and WL01 strains, which affected the specificity of protective virus neutralizing antibodies induced. This was further confirmed by cross-protection studies in ducks immunized at 2 d of age with whole-virus inactivated oil emulsion vaccines containing DE13 strain or WL01 strain as monovalent vaccine or both strains as bivalent vaccine. Protection against clinical disease with the monovalent vaccine was fully effective against homologous virus challenge at 2 weeks after vaccination, whereas protection against heterologous virus challenge was significantly lower (p < 0.001). Only the bivalent inactivated vaccine containing both strains protected birds against the two novel duck reovirus that cause disease in ducks. The results showed that vaccination of the inactivated vaccine at 2 day of age induced rapid immunity (within 2 weeks after vaccination) with complete clinical protection in ducks, the high level of neutralizing antibody could be maintained until 60 days-old. Pre-laying ducks immunization with two doses of bivalent inactivated vaccine could induce passive immunity in offspring ducks, and 100 % protection could be obtained through maternal antibody, which could be maintained until 21 days of age., 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 © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Cross-protection occurs when exposure to one stressor confers heightened tolerance against a different stressor. Alternatively, exposure to one stressor could result in reduced tolerance against other stressors. Although cross-protection has been documented in a wide range of taxa at juvenile and adult life stages, whether early developmental exposure to a stressor confers cross-protection or reduced tolerance to other stressors later in life through developmental plasticity remains largely unexplored. In this study, we examined whether altered temperature during embryonic development results in developmental plasticity in upper thermal tolerance or hypoxia tolerance using a small topminnow, Fundulus heteroclitus, and examined potential underlying molecular mechanisms. We incubated embryos at one of two ecologically relevant temperatures (20°C or 26°C) until hatch. Once hatched, fish were raised at a common temperature of 20°C for 1 year, and tolerance was assessed in both juveniles (6 months) and early adults (1 year). Developmental temperature had no significant effect on thermal tolerance (CTmax) in juvenile fish, or on the transcript abundance of thermal tolerance-related genes (constitutive heat shock proteins, hsc70, hsp90b). In contrast, reduced developmental temperature decreased hypoxia tolerance but increased transcript levels of the hypoxia inducible factor hif1α in juvenile fish but the effects were less evident in older fish. Overall, we found no indication of developmental plasticity for thermal tolerance, but there was evidence of negative impacts of lower developmental temperature on hypoxia tolerance in juveniles associated with changes in gene expression, providing evidence of developmental plasticity across stressors and levels of organization., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2025. Published by The Company of Biologists.)

Chagas disease remains a significant public health concern, with limited treatment options and an urgent need for novel preventive strategies. Extracellular vesicles (EVs) from Trypanosoma cruzi have been shown to modulate host immune responses, often favoring parasite persistence. In this study, we characterized EVs derived from the non-pathogenic trypanosomatids Trypanosoma rangeli and Phytomonas serpens and evaluated their potential as immunogens capable of inducing cross-protection against T. cruzi infection. Isolated EVs were characterized by Nanoparticle Tracking Analysis (NTA) and electron microscopy. A comparative proteomic analysis of EVs was performed using Mass Spectrometry-Based Proteomic Analysis (LC-MS/MS). The effects of EVs on immunomodulation and T. cruzi infection were assessed through in vitro and in vivo assays, using peripheral blood mononuclear cells (PBMCs) and BALB/c mice. The proteomic analysis identified shared proteins between the EVs of T. rangeli , P. serpens , and T. cruzi , including immunogenic candidates such as calpain-like cysteine peptidase and elongation factor 2. In vitro, pre-stimulation with the T. rangeli EVs reduced infection rates of the host cells by T. cruzi . In vivo, immunization with the EVs from T. rangeli and P. serpens led to a significant reduction in parasitemia in the BALB/c mice challenged with T. cruzi , though this did not translate into improved survival compared to controls. Interestingly, the EVs from T. cruzi also reduced parasitemia but did not confer protection against mortality. These findings suggest that while non-pathogenic trypanosomatid EVs exhibit potential immunogenic properties and can reduce parasitic load, their efficacy in preventing disease progression remains limited. Further research is needed to explore the mechanisms underlying these effects and to optimize EV-based strategies for protective immunity against Chagas disease.

Messenger RNA vaccines based on lipid nanoparticles (mRNA-LNPs) are promising vaccine modalities. However, mRNA-LNP vaccines frequently cause adverse reactions such as swelling and fever in humans, partly due to the inflammatory nature of LNP. Modification of the ionizable lipids used in LNPs is one approach to avoid these adverse reactions. Here, we report the development of mRNA-LNP vaccines with better protective immunity and reduced adverse reactions using LNPs, which contain a disulfide (SS)-cleavable bond and pH-activated lipid-like materials with oleic acid (ssPalmO) as an ionizable lipid (LNP ssPalmO ). We used mRNA expressing H5N1 subtype high-pathogenicity avian influenza virus-derived hemagglutinin or neuraminidase to generate mRNA-LNP vaccines against H5N1 influenza. Compared with conventional LNPs, mRNA-LNP ssPalmO induced comparable antigen-specific antibodies and better interferon-γ (IFN-γ)-producing T helper type 1 responses in mice. Both mRNA-LNP ssPalmO and conventional mRNA-LNPs conferred strong protection against homologous H5N1 virus challenge. In addition, mRNA-LNP ssPalmO showed better cross-protection against heterologous H5N1 virus challenge compared with conventional mRNA-LNPs. Furthermore, we observed that mRNA-LNP ssPalmO induced less-inflammatory responses (e.g., inflammatory cytokine production, vascular hyperpermeability) and fewer adverse reactions (e.g., weight loss, fever) compared with conventional mRNA-LNPs. These results suggest that mRNA-LNP ssPalmO would be a safe alternative to conventional vaccines to overcome mRNA-LNP vaccine hesitancy., Competing Interests: Declaration of interests T.S., H.T., T.W., H.A., and Y.Y. filed a patent application related to the content of the manuscript (US63/515,413 and PCT/JP2024/026712). H.T. and H.A. are the named inventors on a patent (WO2019/188867). Y.Y. is an employee of The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Enhancing protective immunity in the respiratory tract is crucial to combat influenza infection and transmission. Developing mucosal universal influenza vaccines requires effective delivery platforms to overcome the respiratory mucosal barrier and stimulate appropriate innate immune reactions, thereby bridging adaptive immune responses with minimal necessary inflammation. Meanwhile, the vaccine platforms must be biocompatible. This study employed cell-derived extracellular vesicles (EVs) as a mucosal universal influenza vaccine platform. By conjugating influenza hemagglutinin (HA) onto EV surfaces through HA-receptor interaction, we achieved an upside-down (inverted) influenza HA configuration that exposed the conserved HA stalk region while partially hiding the globular head domain. Intranasal immunization with the resulting EVs induced robust HA stalk- and virus-specific serum antibody and mucosal immune responses in mice, protecting against heterologous virus infection. Notably, EVs derived from the lung epithelial cell line A549 induced superior cross-reactive antibodies and enhanced protection upon intranasal immunization. EVs conjugating multivalent HA elicited broadly cross-reactive antibody and cellular responses against different influenza strains. Our results demonstrated that EVs conjugating multiple inverted HAs represented an effective strategy for developing a mucosal universal influenza vaccine., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Influenza A viruses (IAVs) cause seasonal influenza epidemics and pose significant threats to public health. However, seasonal influenza vaccines often elicit strain-specific immune responses and confer little protection against mismatched strains. There is an urgent need to develop universal influenza vaccines against emerging and potentially re-emerging influenza virus infections. Multiepitope vaccines combining multiple conserved epitopes can induce more robust and broader immune responses and provide a potential solution., Results: Here, we demonstrated that an HA chimeric multiepitope nanoparticle vaccine, delivered intranasally conferred broad protection against challenges with various influenza viruses in mice. The nanoparticle vaccine co-expresses the ectodomain of haemagglutinin (H), three repeated highly conserved ectodomains of matrix protein 2 (M), and the M-cell-targeting ligand Co4B (C) in a baculovirus-insect cell system. These elements (C, H and M) were presented on the surface of self-assembling ferritin (f) in tandem to generate a nanoparticle denoted as CHM-f. Intranasal vaccination with CHM-f nanoparticles elicited robust humoral and cellular immune responses, conferring complete protection against a variety of IAVs, including the A/PR8/34 H1N1 strain, the swine flu H3N2 strain, the avian flu H5N8 strain, and H9N2. When CHM-f nanoparticles adjuvanted with CpG IAMA-002, the weight loss protective effect, cellular immune responses and mucosal IgA responses were significantly augmented. Compared with controls, mice immunized with CHM-f nanoparticles with or without CpG IAMA-002 showed significant reductions in weight loss, lung viral titres and pathological changes., Conclusions: These results suggest that CHM-f nanoparticle with or without CpG IAMA-002 is a promising candidate as a universal influenza vaccine., Competing Interests: Declarations. Ethics approval and consent to participate: All animal procedures were approved by the Northwest A&F University Institutional Animal Care and Use Committee (IACUC). The study was conducted in accordance with local legislation and institutional requirements. Consent for publication: All the authors agreed to submit this manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Between 2009-2021, bivalent human papillomavirus (HPV) vaccination was offered to girls in the Netherlands. We studied the impact of girls-only HPV vaccination on genital HPV prevalence among young adults., Methods: PASSYON (2009-2021) is a study among sexual health clinic clients aged 16-24 years old. Questionnaires elicited data on demographics, sexual behavior, and HPV vaccination status. Genital samples were analyzed using a PCR-based assay (SPF10-LiPA25). Prevalence trends of 12 high-risk genotypes were assessed as adjusted average annual change (aAAC), estimated using Poisson generalized estimating equations models. The relation between aAAC and phylogenetic distance to HPV-16/18 was assessed by means of regression and rank correlation analysis. Data were collected from 8889 females and 3300 heterosexual males (HMs)., Results: Among females (irrespective of vaccination status), prevalences of HPV-16/18/31/33/35/45 decreased significantly over time. Increasing trends were observed for HPV-39/52/56. Among both HMs and unvaccinated females (54.3%), HPV-16/18 significantly declined, as did HPV-31 among HMs. Contrastingly, HPV-52/58 increased significantly among HMs and unvaccinated females. The type-specific aAAC correlated well with the phylogenetic distance to HPV-16/18., Conclusions: During 12 years of girls-only bivalent HPV vaccination in the Netherlands, decreasing trends of the vaccine types and cross-protected types were observed among females. Herd protection of vaccine types was observed for HMs and unvaccinated females, and 1 cross-protected type for HMs. Increasing prevalence trends of HPV types with large phylogenetic distance to the vaccine types might indicate type replacement., Competing Interests: Potential conflicts of interest. The institution of M. F. S. v. d. L. and J. C. M. H. received study funding for an investigator-initiated study from GSK. M. F. S. v. d. L. and J. A. B. are both principal investigators on this study. M. F. S. v. d. L. served on advisory boards of MSD and Novosanis. J. A. B. serves on an advisory board for GSK. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Influenza viruses pose a significant threat to global public health. Several influenza pandemic outbreaks have had serious economic and public health implications. Current influenza virus vaccines generally provide strain-specific protection and must be rapidly produced annually to match the circulating viruses. Developing influenza vaccines that confer protection against a broad range of viruses will have a positive impact on public health. In this study, we aimed to develop a ferritin-based influenza nanoparticle vaccine with a broad protective spectrum to enhance the immune response against diverse influenza viruses., Results: We generated an adjuvant-free, self-assembling nanoparticle vaccine against diverse influenza A viruses. This nanoparticle vaccine displayed multi-antigen targets on the surface of Helicobacter pylori ferritin, which consists of the ectodomain of hemagglutinin of the H3N2 virus and three tandem highly conserved influenza M1 epitopes fused with the universal helper T-cell epitope PADRE, named HMP-NP. HMP-NPs were expressed in a soluble form in the baculovirus-insect cell system and self-assembled into homogeneous nanoparticles. Animal immunization studies showed that the HMP-NP nanovaccine elicited 4-fold higher haemagglutination inhibition (HAI) titers than inactivated influenza vaccine. And neutralization titers induced by HMP-NPs against the H3N2 virus and heterologous strains of the H1N1 and H9N2 viruses were ~8, 12.4 and 16 times higher than inactivated influenza vaccine, respectively. Meanwhile, we also observed that the number of IFN-γ- and IL-4-secreting cells induced by HMP-NPs were ~2.5 times higher than inactivated influenza vaccine. Importantly, intranasal immunization with HMP-NPs, without any adjuvant, induced efficient mucosal IgA responses and conferred complete protection against the H3N2 virus, as well as partial protection against the H1N1 and H9N2 viruses and significantly reduced lung viral loads., Discussion: Overall, our results indicated that the self-assembled nanovaccines increased the potency and breadth of the immune response against various influenza viruses and are a promising delivery platform for developing vaccines with broader protection against emerging influenza viruses and other pathogens., Competing Interests: Authors SG,BW and ED were employed by Yangling Carey Biotechnology Co., Ltd. Authors CP and ED were employed by Chengdu NanoVAX Biotechnology 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 © 2025 Zhao, Guo, Liu, Wang, Wang, Peng and Du.)

Given the surge in mpox outbreaks in 2022 and the advancements in domestic and international vaccine research, the effectiveness of smallpox vaccines in providing cross-protection against mpox remains crucial. Having learned from the COVID-19 pandemic, it is significant to continue evaluating existing vaccines to ensure their safety and efficacy. Developing new vaccines for widespread use against mpox and its emerging strains also serves as a preventive strategy in the ongoing battle against this dynamic infection. Here's an opportunity to control human-to-human transmission, give short deadlines, and avoid vaccine disparity. Public health systems must take decisive action to prevent the global spread of mpox, particularly among vulnerable groups. This action should include strengthening global surveillance, improving vaccine access, and ensuring equitable distribution, particularly in resource-poor settings, to prevent future outbreaks. This review aims to assess recent advancements and barriers in mpox vaccine development, emphasizing cross-protection and equitable vaccine distribution in resource-poor settings., (© The Author(s), 2025.)

Background/Objectives : Porcine reproductive and respiratory syndrome virus (PRRSV) has a major impact on swine productivity. Modified-live vaccines (MLVs) are used to aid in control. We investigated the cross-protection provided by a lineage 7 PRRSV MLV against a lineage 1 isolate under laboratory conditions and a lineage 3 challenge under field conditions in Taiwan. Methods : In the first study, thirty PRRS antibody-negative conventional piglets were vaccinated via the intramuscular (IM) or the intradermal (ID) route, with the control group receiving a placebo. Four weeks after immunization, all groups were challenged with a Taiwanese lineage 1 strain. The standard protocol for detection of reversion to virulence was applied to the vaccine strain in the second study, using sixteen specific pathogen-free piglets. In the third study, on an infected pig farm in Taiwan (lineage 3 strain), three hundred piglets were randomly selected and divided into three groups, each injected with either the PrimePac ® PRRS vaccine via the IM or the ID route, or a placebo. Results : In the first study, both vaccinated groups demonstrated reduced viraemia compared to the control group. The second study demonstrated that the MLV strain was stable. In the third study, piglet mortality, average daily weight gain, and pig stunting rate were significantly improved in the vaccinated groups compared to the control group. Conclusions : PrimePac ® PRRS is safe to use in the field in the face of a heterologous challenge, successfully providing cross-protection against contemporary lineage 1 and lineage 3 PRRSV strains from Taiwan.

Influenza A matrix protein 2 (M2e) and neuraminidase (NA) antigens are known to play important roles in mounting a broad range of protection. Nonetheless, the protective efficacy of the VLP vaccines co-expressing both M2e and NA antigens has not been explored. In this study, we generated 2020/2021 seasonal influenza H3N1 VLPs that co-expressed either M2e5x (H3N1M2e5x) or N2 (H3N1N2 VLP) antigens. The protective efficacy of these VLPs was assessed by challenge infection with heterologous H3N2 and heterosubtypic H1N1 and H5N1 viruses in mice. Both VLP formulations induced cross-protection against distinct viruses, H3N1M2e5x VLPs elicited higher levels of cross-reactive IgG in sera against H1N1 and H5N1 viruses than H3N1N2 VLPs. Compared to H3N1N2 VLPs, H3N1M2e5x VLPs also induced substantially enhanced germinal center B cell responses while inhibiting IFN-γ production in the lungs. Importantly, H3N1M2e5x VLPs significantly reduced the lung virus titers upon H1N1, H3N2, and H5N1 challenge infections. These results indicated that VLPs comprising the M2e5x antigen are a promising vaccine design strategy that could aid in the pursuit of a universal influenza vaccine., 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.)

Two vaccination-challenge trials were performed using a commercial infectious bronchitis virus (IBV) BR1 vaccine, given alone or combined with a commercial IBV Mass vaccine against challenges with IBV M41, 793B, D388 (QX), Q1, Brasil-1 or Variant 2 challenge viruses, which includes the IB viruses that are dominant in South America. The efficacy of the vaccines against the challenge viruses was investigated by determination of the ciliary activity of the tracheal epithelium after challenge. The level of protection induced by the IBV BR1 vaccine alone against the six IBV challenge strains, of which five were of heterologous genotypes, varied from 50% to 100% with an average of 80%. The level of protection induced by the combination of the IBV BR1 and IBV Mass vaccines against the six IBV challenge strains, of which four were of heterologous genotypes, varied from 80% to 100% with an average of 92%. Vaccination with IBV BR1 alone provided a high level of protection against most tested challenge viruses, though the combination of IBV BR1 and IBV Mass was more consistent, showing less variation and compliance with the criterium mentioned in the European Pharmacopoeia 10th edition (at least 80% protection) for all tested challenge viruses. These trials show that vaccination with a combination of IBV BR1 and IBV Mass vaccines provides high levels of protection against the circulating IBV strains in South America.

Background: Enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi A in addition to gastroenteritis and invasive disease, predominantly attributable to nontyphoidal Salmonella serovars Typhimurium and Enteritidis, are major causes of death and disability across the globe. A broad-spectrum vaccine that protects against disease caused by typhoidal and nontyphoidal serovars of Salmonella is not available for humans but would prevent a considerable burden of disease worldwide., Methods: We previously developed a broad-spectrum vaccine for Gram-negative bacteria that is based on the inner core domain of detoxified Escherichia coli O111, Rc (J5) mutant lipooligosaccharide, a highly conserved antigen across Gram-negative bacteria, complexed with an outer membrane protein of group B Neisseria meningitidis. In this study, mice and rabbits were immunized with the J5 core/outer membrane protein subunit vaccine. We assessed the cross-reactivity of antisera with various Salmonella species lipopolysaccharides and the protective efficacy of passive and active immunization with J5 vaccine against experimental nontyphoidal Salmonella infection in mice., Results: Vaccination with J5 induced IgG responses that strongly recognized lipopolysaccharide from both typhoidal and nontyphoidal Salmonella and imparted a survival benefit against lethal heterologous challenges with S. Typhimurium and S. Enteritidis. Additionally, passive transfer studies with rabbit hyperimmune sera raised against the J5 vaccine revealed that anti-core antibodies were protective against lipopolysaccharide challenge in D-galactosamine-sensitized mice., Conclusions: Our findings support the development of core glycolipids as a novel Salmonella vaccine candidate. Further investigation is warranted to determine the efficacy of the J5 core/outer membrane protein vaccine against other Salmonella serovars of concern., (© 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.)

The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents. The real-world safety profile of 4CMenB is consistent with prelicensure reports. Use of the endogenous complement human serum bactericidal antibody (enc-hSBA) assay against 110 MenB strains may enable assessment of the immunological effectiveness of multicomponent MenB vaccines in clinical trial settings. Equitable access to 4CMenB vaccination is required to better protect all age groups, including older adults, and vulnerable groups through comprehensive immunization policies.

Vaccines that cross-protect across serovars of Salmonella enterica ( Salmonella ) would be a beneficial intervention against emerging and persistent Salmonella isolates of concern for the turkey industry. The 2017-2019 foodborne outbreak of Salmonella enterica serovar Reading ( S . Reading) revealed the need for effective control of this serovar in turkey production. This study evaluated two live-attenuated Salmonella vaccines, an internally developed cross-protective vaccine and a commercially available vaccine, against an outbreak-associated strain of S . Reading in turkeys. At 1 day and 3 weeks of age, male turkey poults were either mock-vaccinated with phosphate buffered saline (PBS) or given one of the vaccines by oral gavage (primary and booster) or aerosol spray (primary) then drinking water (booster). At 7 weeks of age, poults were challenged with 10 9 colony forming units (CFU) of S . Reading; a mock-vaccinated group was mock-challenged with PBS. Colonization of the cecal contents and cecal tonsil was 1.5-3 log 10 CFU/g lower in vaccinated birds than mock-vaccinated birds at 7 and/or 14 days post-inoculation (DPI). Salmonella dissemination to the spleen was significantly reduced by both vaccines. Gene expression of intestinal transporters (such as SCNN1B and SLC10A2 ) and tight junction proteins was significantly decreased in the turkey cecal tonsil transcriptome at 2 DPI with S . Reading. Vaccination with either vaccine mitigated most cecal tonsil gene expression responses to S . Reading challenge. Therefore, both the internally developed vaccine and commercial vaccine were cross-protective against colonization and dissemination, and both were able to limit transcriptional changes from challenge in intestinal health-related genes in the cecal tonsil, thereby providing vaccination efficacy and impact data against S . Reading in turkeys., 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 Monson, Gurung, Bearson, Whelan, Trachsel, Looft, Sylte and Bearson.)

Background/Objective: Duck virus hepatitis (DVH), caused by duck hepatitis A virus (DHAV), poses significant challenges to duck farming due to high mortality rates in young ducklings. Despite the widespread use of live attenuated vaccines, the genetic diversity within DHAV strains has diminished their cross-protection efficacy. This study aimed to evaluate the cross-protective efficacy of current DHAV-1 and DHAV-3 vaccines against genetically divergent wild strains. Methods: Phylogenetic analyses of the VP1 genes from DHAV-1 and DHAV-3 were conducted. Both DHAV-1 and DHAV-3 vaccines were tested in ducklings, with and without maternal-derived antibodies (MDA), through challenge trials with homologous and heterologous strains. Results: In the phylogenetic analysis, compared to vaccine strains, DHAV-1 and DHAV-3 field variant strains were classified into different genotypes. In ducklings without MDA, the DHAV-1 vaccine provided 60% survival against homologous strains by 2 days post-vaccination (DPV) and complete protection by 4 DPV, while survival rates against heterologous strains ranged from 40 to 60%. In ducklings with MDA, the DHAV-1 vaccine provided full protection with an additional vaccination for day-old ducklings against heterologous strains. The DHAV-3 vaccine conferred complete protection against both homologous and heterologous strains by 2 DPV, regardless of MDA presence. Conclusions: The DHAV-3 vaccine demonstrated robust cross-protection across genotypes, while the DHAV-1 vaccine showed limitations against genetically divergent strains. These findings highlight the necessity for genotype-matched vaccines and optimized immunization strategies to enhance protection against evolving DHAV field strains.

Coccidiosis is one of the most significant diseases affecting the rabbit industry and is caused by Eimeria . In a previous study, we identified a new species of Eimeria kongi ( E. kongi -ZJK) from the northern region of China (Zhangjiakou, Hebei Province) and studied its pathogenicity and immunogenicity. The aim of this study was to evaluate the pathogenicity, immunogenicity, and cross-immunogenicity from different geographical isolates of E. kongi for vaccine development. Two geographical isolates of E. kongi -QD from Qingdao, Shandong Province (eastern China), and E. kongi- CD from Chengdu, Sichuan Province (southwestern China), were isolated and identified. The pathogenicity, immunogenicity, and cross-immunogenicity among the three geographical isolates were evaluated. The pathogenicity results showed that after infecting rabbits with doses of 1 × 10 3 or fewer sporulated oocysts of E. kongi -QD and E. kongi -CD, the rabbits exhibited clinical symptoms but recovered quickly, indicating lower pathogenicity. Immunogenicity studies revealed that after immunizing rabbits with 1 × 10 3 sporulated oocysts of E. kongi -QD and E. kongi -CD for 14 days, followed by challenge with 1 × 10 4 homologous sporulated oocysts, the oocyst reduction rates in the immunized groups were 99.39% and 99.12%, respectively, compared with the non-immunized groups, demonstrating good immunogenicity. In cross-immunogenicity studies, rabbits were immunized with 1 × 10 3 sporulated oocysts of E. kongi -ZJK, E. kongi -QD, or E. kongi -CD and then challenged with 1 × 10 4 sporulated oocysts of heterologous isolate. The immunized groups showed no significant clinical symptoms, and the oocyst reduction rates ranged from 55.9% to 98.4%. E. kongi -CD exhibited cross-protection against E. kongi -ZJK and E. kongi -QD, making it an ideal candidate formulation for vaccine development.

Mycoplasma hyorhinis is a highly prevalent pathogen in pig farms worldwide, causing polyserositis and polyarthritis, resulting in great economic losses. Previous genotyping and pathogenic studies have revealed significant genetic and antigenic diversity among M. hyorhinis strains. While there are reports on M. hyorhinis vaccine development, the cross-protection between different M. hyorhinis strains has not been clarified. In this study, two M. hyorhinis strains (HEF-16 and JS-54), belonging to different sequence types, were inactivated to produce vaccines. Pigs were vaccinated respectively and subsequently infected with strain HEF-16. The protection against challenge with homologous or heterologous strains was determined and compared. Both vaccinated groups of pigs exhibited a high antibody titer two weeks after the first vaccination, and significant decreases in pathogen load in joints, along with an increase in average daily weight gain compared to the challenged group after M. hyorhinis challenge. Pigs immunized with the HEF-16-derived vaccine showed a significant reduction in joint swelling and lameness, similar to pigs immunized with the JS-54-derived vaccine. At necropsy, animals in the challenged group exhibited moderate-to-severe polyserositis and arthritis, whereas pathological changes were greatly reduced in animals from the vaccinated groups. No significant differences were observed in clinical symptoms nor pathological damages between the two vaccinated groups. Overall, our study demonstrates the effective protection of the inactivated M. hyorhinis vaccines against challenges with homologous or heterologous strains in commercial pigs. This indicates a promising clinical application prospect for inactivated bacterin vaccines in preventing M. hyorhinis-related diseases in pig farms., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

The increasing incidence of diseases caused by Coxsackievirus A6 (CV-A6) and the presence of various mutants in the population present significant public health challenges. Given the concurrent development of multiple vaccines in China, it is challenging to objectively and accurately evaluate the level of neutralizing antibody response to different vaccines. The choice of the detection strain is a crucial factor that influences the detection of neutralizing antibodies. In this study, the National Institutes for Food and Drug Control collected a prototype strain (Gdula), one subgenotype D1, as well as 13 CV-A6 candidate vaccine strains and candidate detection strains (subgenotype D3) from various institutions and manufacturers involved in research and development. We evaluated cross-neutralization activity using plasma from naturally infected adults ( n  = 30) and serum from rats immunized with the aforementioned CV-A6 strains. Although there were differences between the geometric mean titer (GMT) ranges of human plasma and murine sera, the overall trends were similar. A significant effect of each strain on the neutralizing antibody test (MAX/MIN 48.0 ∼16410.3) was observed. Among all strains, neutralization of the S112 strain by 15 different sera resulted in higher neutralizing antibody titers (GMT S112  = 132.0) and more consistent responses across different genotypic immune sera (MAX/MIN = 48.0). Therefore, S112 may serve as a detection strain for NtAb testing in various vaccines, minimizing bias and making it suitable for evaluating the immunogenicity of the CV-A6 vaccine.

Poultry products are an important source of foodborne Salmonella infections in humans. Amongst these, the prevalence of S. Infantis is rising. In this study, the protection efficacy of an authorized live-attenuated S. Typhimurium vaccine against S. Infantis, was examined using a seeder-bird model in broilers. Vaccinated birds displayed a significantly lower colonization of S. Infantis bacteria in the caeca compared to the non-vaccinated counterparts ( P  = 0.017), with no significant differences observed in the spleen among the groups, three days post-infection. Thirty-two days post-infection, the disparity in average S. Infantis concentration between all-vaccinated and non-vaccinated birds was significant in both caeca ( P  = 0.0003) and spleen ( P  = 0.0002). Interestingly, a third group, consisting of seeder birds that were not vaccinated but housed with vaccinated penmates, exhibited significantly lower S . Infantis levels in both caeca ( P  = 0.0014) and spleen ( P  < 0.0001) compared to the non-vaccinated group. These findings underscore the potential of a live-attenuated S. Typhimurium vaccine administered to 2-day-old chicks in conferring protection against S. Infantis in broilers up to slaughter age.

Genetic changes have occurred in the genomes of prevalent African swine fever viruses (ASFVs) in the field in China, which may change their antigenic properties and result in immune escape. There is usually poor cross-protection between heterogonous isolates, and, therefore, it is important to test the cross-protection of the live attenuated ASFV vaccines against current prevalent heterogonous isolates. In this study, we evaluated the protective efficacy of the ASFV vaccine candidate HLJ/18-7GD against emerging isolates. HLJ/18-7GD provided protection against a highly virulent variant and a lower lethal isolate, both derived from genotype II Georgia07-like ASFV and isolated in 2020. HLJ/18-7GD vaccination prevented pigs from developing ASF-specific clinical signs and death, decreased viral shedding via the oral and rectal routes, and suppressed viral replication after challenges. However, HLJ/18-7GD vaccination did not provide solid cross-protection against genotype I NH/P68-like ASFV challenge in pigs. HLJ/18-7GD vaccination thus shows great promise as an alternative strategy for preventing and controlling genotype II ASFVs, but vaccines providing cross-protection against different ASFV genotypes may be needed in China.

The H5N1 subtype highly pathogenic avian influenza virus (HPAIV) reveals high variability and threatens poultry production and public health. To prevent the spread of H5N1 HPAIV, we developed an H5N1 virus-like particle (VLP) vaccine based on the insect cell-baculovirus expression system. Single immunization of the H5N1 VLP vaccines induced high levels of HI antibody titres and provided effective protection against homologous virus challenge comparable to the commercial inactivated vaccine. Meanwhile, we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the adjuvants ISA 201 and ISA 71 and evaluated whether the two adjuvants could induce broadly protective immunity. The ISA 71 adjuvanted vaccine induced significantly higher levels of Th1 and Th2 immune responses and provided superior cross-protection against antigenically divergent H5N1 virus challenge than the ISA 201 adjuvanted vaccine. Importantly, increasing the vaccine dose could further enhance the cross-protective efficacy of H5N1 VLP vaccine and confer completely sterilizing protection against antigenically divergent H5N1 virus challenge, which was mediated by neutralizing antibodies. Our results suggest that the H5N1 VLP vaccine can provide broad-spectrum protection against divergent H5N1 influenza viruses as determined by adjuvant and vaccine dose.

Background: Glaesserella parasuis (G. parasuis) is the primary agent of Glässer's disease, significantly affecting nursery and early fattening piglets. Current prophylactic measures, mainly serovar-specific bacterins administered to sows, are limited by maternal immunity, which can interfere with active immunization in piglets. Subunit vaccines containing G. parasuis-specific antigenic molecules show promise but are not yet commercially available. Transferrin-binding proteins (Tbp), which enable G. parasuis to acquire iron in low-iron environments like mucosal surfaces, have been proposed as potential vaccine antigens. The mucosal administration of a TbpB-based subunit vaccine could provide a promising solution to overcome the limitations posed by maternal immunity, offering an effective approach to control the disease in weaning piglets. This study, conducted in two phases, primarily evaluates (days 0-45) the immunogenicity of a two-dose oral mucosal TbpB-based subunit vaccine (TbpB Y167A ) administered to colostrum-deprived piglets, and subsequently (days 45-52), its heterologous protection by challenging these piglets with four G. parasuis clinical isolates from different TbpB clusters (I, III) and serovars (SV1, SV4, SV5, SV7) recovered from Spanish pig farms., Results: The oral mucosal administration of the two-dose TbpB-based vaccine induced a robust humoral immune response in immunized colostrum-deprived piglets, significantly increasing IgA and IgM concentration 15 days after the second dose (p < 0.01). Upon challenge with four G. parasuis clinical isolates, the vaccine demonstrated heterologous protection, markedly improving survival rates (OR: 8.45; CI 95%: 4.97-14.36) and significantly reducing clinical signs and lesions, regardless of the TbpB cluster and serovar. The vaccine reduced G. parasuis colonization in the respiratory tract (p < 0.0001) and G. parasuis systemic target tissues, like tarsus and carpus joints, liver, and brain (p < 0.05). Immunohistochemical analysis showed a lower macrophage count in different lung locations of immunized piglets (p < 0.0001)., Conclusions: This study demonstrates that oral mucosal administration of the TbpB Y167A subunit vaccine in piglets provides effective heterologous protection against diverse virulent European G. parasuis field isolates, significantly reducing bacterial colonization and dissemination. This vaccine offers a promising alternative to traditional bacterins, overcoming limitations due to maternal immunity, and represents a strong candidate for universal vaccination against Glässer's disease., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures involving animals were approved by the institutional bioethical committee (Reference Number OEBA-ULE-003–2022) and performed according to European regulations regarding animal welfare and protection of animals used for experimental and other scientific purposes. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

According to sparse information from various countries, the seasonal influenza virus circulation has drastically decreased during the COVID-19 pandemic. Here, we show the cross-reactivity of anti-SARS-CoV-2 antibodies against influenza viruses. Plasma samples were collected from 311 SARS-CoV-2 infected individuals. The samples were tested for antibody titers against SARS-CoV-2 by ELISA and seasonal influenza virus strains (influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria) using a Hemagglutination Inhibition Assay (HAI). In addition, SARS-CoV-2 antibody-positive but Influenza antibody-negative samples (n = 16) were investigated to determine the SARS-CoV-2 antibody-neutralizing potential against influenza viruses by microneutralization (MN) assay. The SARS-CoV-2 genomes were sequenced using Illumina next-generation sequencing, and an in-silico protein structural analysis was performed to identify epitope and antibody binding similarities between SARS-CoV-2 and influenza viruses. Among 16 samples that didn't contain antibodies against Influenza A strains (H1N1 and H3N2), five showed high (MN titer≥20), and six showed moderate (MN titer≥10) capability to neutralize Influenza A. Subsequent in-silico analysis revealed that most efficient binding (>8 kcal/mol) was found between the antibodies of SARS-CoV-2 delta variant (ΔG) with influenza A/H1N1 HA (Hemagglutinin), A/H3N2 HA, A/H1N1 NA (Neuraminidase), and A/H3N2 NA glycoproteins with -12.4, -9.3, -10.1, and -11.7 kcal/mol, respectively. This investigation revealed that neutralizing antibodies of the delta variant cross-reacted with the Influenza A virus, which might protect against influenza viruses and reduce and shift the seasonal influenza circulation during the COVID-19 pandemic. Our findings warrant further study to explain the probable mechanisms of this cross-reactivity., Competing Interests: 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., (© 2024 International Centre for Diarrheal Disease Research, Bangladesh.)

In recent years, NADC34-like strains of porcine reproductive and respiratory syndrome virus have gradually emerged as mainstream strains on Chinese pig farms. These strains have high mutation rates and can recombine with local strains, representing great challenges to prevention and control efforts. Previously, a new recombinant NADC34-like subtype strain was isolated in our laboratory. Herein, we evaluated the cross-protective effect of the VR2332 modified live virus (MLV) against the novel NADC34-like recombinant strain using the immune challenge protection test in piglets and sows. The results revealed that immunization with the vaccine in piglets significantly reduced viremia, lung damage and stimulated the production of PRRSV-N antibodies. In the sow challenge experiment, one abortion and one death were recorded in the positive control group, and the survival rate of offspring was only 25%. However, there were no sow deaths or abortions in the immunization group during the experiment, and the average piglet survival rate was high at 76.5%. In general, the VR2332 MLV confers a certain extent of cross-protection against the NADC34-like recombinant strain, providing an effective reference and guidance for prevention and control efforts and clinical vaccine use., Competing Interests: Authors YW, LL, LY, HZ, BR, LW and QL were employed by company Wen’s Food Group. The remaining author declares 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 Wu, Lin, Gao, Zheng, Yin, Zhao, Ren, Wang and Li.)

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases affecting the pig industry worldwide and is caused by the PRRS virus (PRRSV), which has complex genetic variation due to frequent mutations, indels, and recombination. The emergence of PRRSV L1C.5 in 2020 in the United States has raised worldwide concerns about PRRSV with the RFLP 1-4-4 pattern and lineage 1C. However, studies on the pathogenic characteristics, epidemiological distribution, and effectiveness of vaccines against PRRSV with L1C and RFLP1-4-4 pattern in China are still insufficient. In this study, a novel recombinant variant of PRRSV with RFLP 1-4-4 and lineage 1C features, different from L1C.5 in the United States, was isolated in China in 2021. In pathogenicity experiments in specific pathogen-free piglets or farm piglets, 60-100% of artificially infected experimental piglets died with high fever and respiratory symptoms. Inflammatory cytokine and chemokine levels were upregulated in infected piglets. A commercially modified live vaccine against highly pathogenic PRRSV did not provide effective protection when the vaccinated piglets were challenged with the novel L1C-1-4-4 variant. Therefore, this strain merits special attention when devising control and vaccine strategies. These findings suggest that extensive joint surveillance is urgently needed and that vaccine strategies should be updated to prevent the disease from spreading further., (© 2024. The Author(s).)

Most coronavirus vaccines focus on the spike (S) antigen, but the frequent mutations in S raise concerns about the vaccine efficacy against new variants. Although additional antigens with conserved sequences are have been tested, the extent to which these vaccines can provide immunity against different coronavirus species remains unclear. In this study, we assessed the potential of nucleocapsid (N) as a coronavirus vaccine antigen. Immunization with MERS-CoV N induced robust immune responses, providing significant protection against MERS-CoV. Notably, MERS-CoV N elicited cross-reactive T cell responses to SARS-CoV-2 N and significantly reduced lung inflammation following a SARS-CoV-2 challenge in the transient hACE2 mouse model. However, in K18-hACE transgenic mice, the vaccine showed limited protection. Collectively, our findings suggest that coronavirus N can be an effective vaccine antigen against homologous viruses, but its efficacy may vary across different coronaviruses, highlighting the need for further research on pan-coronavirus vaccines using conserved antigens., 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.)

Streptococcosis caused by Streptococcus agalactiae 1a in Nile tilapia (Oreochromis niloticus) is a severe disease challenge for the global supply of tilapia. Currently, the extensive use of antibiotics is the primary curative tool used to minimize the impact of the disease. Vaccination is a prophylactic measure that has been shown to reduce antibiotic use in the aquaculture sector substantially. However, no commercially licensed vaccine against Streptococcus agalactiae 1a is currently available. This study aimed to investigate, through molecular and immunological methods, if Streptococcus agalactiae 1a isolates collected from North America (NAM), Central America (CAM), and Southeast Asia (SEA) were similarly suitable for the development of a potentially effective vaccine to serve the global tilapia farming industry. Our comparative data showed that the Streptococcus agalactiae 1a isolates from NAM, CAM and SEA had similar biochemical profiles, and genetic multi-locus sequence typing (MLST) analysis showed that the NAM and CAM isolates belonged to sequence type 7 (ST-7) and clonal complex 1, while isolates from SEA grouped into three sequence types (ST-1650, ST-500, and ST-7) and two distinct clonal complexes (CC1 and CC12). Isolates from NAM, CAM, and SEA displayed similar antigenic profiles determined by western blotting with polyclonal rabbit antisera, which was supported by in vivo cross-protection studies, showing that fish immunized with vaccines based on SEA and CAM isolates with different genetic MLST profiles were highly protected against cross-challenge using the same bacterial strains for challenge. Overall, the data obtained from our investigations provide strong indications that Streptococcus agalactiae 1a distributed in NAM, CAM, and SEA are serologically uniform pathogens, and vaccines based on isolates of Streptococcus agalactiae 1a from these regions may be suited for vaccination of tilapia worldwide., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bivalent human papillomavirus HPV16/18-AS04 vaccine (Cervarix, GSK) offers direct protection against HPV16/18. Results from randomised controlled trials showed cross protective effects and suggested that declines in some closely related HPV types could be expected in a population with high vaccination coverage., Aim: To evaluate the evidence for cross-protection afforded by HPV16/18-AS04 from post-implementation surveillance in England, and how this complements clinical trial data and post-implementation observations in other countries., Methods: Evidence of cross-protection in young women offered vaccination with HPV16/18-AS04 was gathered from HPV surveillance in England. Data from clinical trials and other post-implementation studies were reviewed., Results: Surveillance using anonymised residual specimens in England found declines of 52.3%, 67.4% and 33.3% against grouped HPV-31/33/45 in 16-18, 19-21, and 22-24 year olds, respectively. Additionally, type-specific analysis found that the prevalence of HPV31 declined to below 1% across all age groups. Cross-protection has been monitored and maintained for over 10 years since the introduction of the vaccination programme. Cross-protection against HPV6/11 was not found in English surveillance outcomes., Conclusion: Surveillance of type-specific infections in vaccine-eligible populations in England has generated clear evidence of cross-protective effects from HPV16/18-AS04 vaccination against high-risk HPV 31/33/45 infections, consistent with other post-implementation observations and confirming and in some ways exceeding expectations from clinical trials., Competing Interests: Declaration of competing interest ANT, VW and EG are employed by GSK. ANT may hold shares. sVW and EG hold shares in GSK. BB was a former GSK employee and he may hold company shares. VW is listed as inventor of patented unrelated vaccines. These authors declare no other financial and non-financial relationships and activities. The Blood Safety, Hepatitis, Sexually Transmitted Infections (STI) and HIV Service at UKHSA has provided GSK with post-marketing surveillance reports on HPV infections; a cost recovery charge is made for these reports. All other authors have no further conflict of interests. Funding statement: GlaxoSmithKline Biologicals SA took in charge all costs associated with the development and publishing of this manuscript., (Copyright © 2024 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

Background: The SARS-CoV-2 virus continuously acquires mutations, leading to the emergence of new variants. Notably, the effectiveness of global vaccination efforts has significantly declined with the rise and spread of the B.1.1.529 (Omicron) variant., Methods: The study used virological, immunological and histological research methods, as well as methods of working with laboratory animals. In this study, we evaluated the Gam-COVID-Vac (Sputnik V), an adenoviral vaccine developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology, and conducted experiments on hemizygous K18-ACE2-transgenic F1 mice. The variants studied included B.1.1.1, B.1.1.7, B.1.351, B.1.1.28/P.1, B.1.617.2, and B.1.1.529 BA.5., Results: Our findings demonstrate that the Sputnik V vaccine elicits a robust humoral and cellular immune response, effectively protecting vaccinated animals from challenges posed by various SARS-CoV-2 variants. However, we observed a notable reduction in vaccine efficacy against the B.1.1.529 (Omicron BA.5) variant., Conclusions: Our results indicate that ongoing monitoring of emerging mutations is crucial to assess vaccine efficacy against new SARS-CoV-2 variants to identify those with pandemic potential. If protective efficacy declines, it will be imperative to develop new vaccines tailored to current variants of the virus.

Plant viral diseases cause great losses in agricultural production. Virus cross-protection is a strategy in which a mild virus is employed to shield plants against subsequent infections by severe viral strains. However, this approach is restricted to protection against the same viruses. In this study, we observed that pre-inoculation with apple geminivirus (AGV) reduced the accumulation of secondarily infected heterologous viruses, such as cucumber mosaic virus, potato virus X, and tobacco mosaic virus in Nicotiana benthamiana, tomato, and pepper plants. Transcriptional expression analysis showed that autophagy-related genes were transcriptionally up-regulated upon AGV inoculation at an early stage of infection. Accordingly, autophagic activity was observed to be elevated following AGV infection. Interestingly, AGV accumulation was reduced in autophagy-deficient plants, suggesting that autophagy activation promotes AGV infection in the plant. Moreover, pre-inoculation with AGV provided cross-protection against infection with a phytopathogenic bacterium (Pseudomonas syringae) and fungus (Botrytis cinerea) in Nicotiana species. In summary, our study showed that AGV, an asymptomatic virus, could protect plants against severe viral, fungal, and bacterial diseases to some extent through the activation of autophagy pathways, highlighting its potential as a biocontrol agent for managing a wide range of plant crop diseases in the field., (© 2024. The Author(s).)

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine viral infectious diseases worldwide. Vaccination is a key strategy for the control and prevention of PRRS. At present, the NADC30-like PRRSV strain has become the predominant epidemic strain in China, superseding the HP-PRRSV strain. The existing commercial vaccines offer substantial protection against HP-PRRSV, but their efficacy against NADC30-like PRRSV is limited. The development of a novel vaccine that can provide valuable cross-protection against both NADC30-like PRRSV and HP-PRRSV is highly important. In this study, an infectious clone of a commercial MLV vaccine strain, GD (HP-PRRSV), was first generated (named rGD). A recombinant chimeric PRRSV strain, rGD-SX-5U2, was subsequently constructed by using rGD as a backbone and embedding several dominant immune genes, including the NSP2, ORF5, ORF6, and ORF7 genes, from an NADC30-like PRRSV isolate. In vitro experiments demonstrated that chimeric PRRSV rGD-SX-5U2 exhibited high tropism for MARC-145 cells, which is of paramount importance in the production of PRRSV vaccines. Moreover, subsequent in vivo inoculation and challenge experiments demonstrated that rGD-SX-5U2 confers cross-protection against both HP-PRRSV and NADC30-like PRRSV, including an improvement in ADG levels and a reduction in viremia and lung tissue lesions. In conclusion, our research demonstrated that the chimeric PRRSV strain rGD-SX-5U2 is a novel approach that can provide broad-spectrum protection against both HP-PRRSV and NADC30-like PRRSV. This may be a significant improvement over previous MLV vaccinations., (© 2024. The Author(s).)

Infections with pathogenic Vibrio strains are associated with high summer mortalities of Pacific oysters Magalana (Crassostrea) gigas, affecting production worldwide. This raises the question of how M. gigas cultures can be protected against deadly Vibro infection. There is increasing experimental evidence of immune priming in invertebrates, where previous exposure to a low pathogen load boosts the immune response upon secondary exposure. Priming responses, however, appear to vary in their specificity across host and parasite taxa. To test priming specificity in the Vibrio - M. gigas system, we used two closely related Vibrio splendidus strains with differing degrees of virulence towards M. gigas. These V. splendidus strains were either isolated in the same location as the oysters (sympatric, opening up the potential for co-evolution) or in a different location (allopatric). We extracted cell-free haemolymph plasma from infected and control oysters to test the influence of humoral immune effectors on bacterial growth in vitro. While addition of haemolypmph plasma in general promoted growth of both strains, priming by an exposure to a sublethal dose of bacterial cells lead to inhibitory effects against a subsequent challenge with a potentially lethal dose in vitro. Inhibitory effects and immune priming was strongest when oysters had been primed with the sympatric Vibrio strain, but inhibitory effects were seen both when challenged with the sympatric as well as against allopatric V. splendidus, suggesting some degree of cross protection. The stronger immune priming against the sympatric strain suggests that priming could be more efficient against matching local strains potentially adding a component of local adaptation or co-evolution to immune priming in oysters. These in vitro results, however, were not reflected in the in vivo infection data, where we saw increased bacterial loads following an initial challenge. This discrepancy might suggests that that it is the humoral part of the oyster immune system that produces the priming effects seen in our in vitro experiments., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

African swine fever (ASF) poses a significant threat to domestic pigs and wild boar (Sus scrofa) populations, with the current epidemiological situation more critical than ever. The disease has spread across five continents, causing devastating losses in the swine industry. Although extensive research efforts are ongoing to develop an effective and safe vaccine, this goal remains difficult to achieve. Among the potential vaccine candidates, live attenuated viruses (LAVs) have emerged as the most promising option due to their ability to provide strong protection against experimental challenges. However, ASF virus (ASFV) is highly diverse, with genetic and phenotypic variations across different isolates, which differ in virulence. This study highlights the limitations of a natural LAV strain (Lv17/WB/Rie1), which showed partial efficacy against a highly virulent and partially heterologous isolate (Arm07; genotype II). However, the LAV's effectiveness was incomplete when tested against a more phylogenetically distant virus (Ken06.Bus; genotype IX). These findings raise concerns about the feasibility of developing a universal vaccine for ASFV in the near future, emphasizing the urgent need to assess the protective scope of LAV candidates across different ASFV isolates to better define their limitations., 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. 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 Cadenas-Fernández, Barroso-Arévalo, Kosowska, Díaz-Frutos, Gallardo, Rodríguez-Bertos, Bosch, Sánchez-Vizcaíno and Barasona.)

Avian pathogenic Escherichia coli (APEC) is a notable pathogen that frequently leads to avian colibacillosis, posing a substantial risk to both the poultry industry and public health. The commercial vaccines against avian colibacillosis are primarily inactivated vaccines, but their effectiveness is limited to specific serotypes. Recent advances have highlighted bacterial membrane vesicles (MV) as a promising candidate in vaccine research. How to produce bacterial MVs vaccines on a large scale is a significant challenge for the industrialization of MVs. The msbB gene encodes an acyltransferase and has been implicated in altering the acylation pattern of lipid A, leading to a decrease in lipid A content in lipopolysaccharides (LPS). Here, we evaluated the immunoprotective efficacy of MVs derived from the LPS low-expressed APEC strain FY26ΔmsbB, which was an APEC mutant strain with a deletion of the msbB gene. The nitrogen cavitation technique was employed to extract APEC MVs, with results indicating a significant increase in MVs yield compared to that obtained under natural culture. The immunization effectiveness was assessed, revealing that FY26ΔmsbB MVs elicited an antibody response of laying hens and facilitated bacterial clearance. Protective efficacy studies demonstrated that immunization with FY26ΔmsbB MVs conferred the immune protection in chickens challenged with the wild-type APEC strain FY26. Notably, LPS low-carried MVs recovered from the mutant FY26ΔmsbB also displayed cross-protective capabilities, and effectively safeguarding against infections caused by O1, O7, O45, O78, and O101 serotypes virulent APEC strains. These findings suggest that MVs generated from the LPS low-expressed APEC strain FY26ΔmsbB represent a novel and empirically validated subunit vaccine for the prevention and control of infections by various APEC serotypes., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study was to evaluate the sufficient safety and effect of the novel influenza vaccine program. It prepared new reassortant influenza virus, with high yield on Vero cells. According to the plaque counting, one dose LAIV was composed with 10 5 PFU of H1, H3, BY, and BV, respectively. Then mixed this LAIV with compound adjuvant, containing 500 μg/mL of carbopol971P and 50 μg/mL of tetanus toxin. That vaccination was called catt-flu. And it employed the GYZZ02 vaccine (commercialized freeze-dried LAIV, listed in China) as cohort analysis control. All mice received two doses of the vaccine, administered on days 0 and 14, respectively. That catt-flu program could induce more cross-protection with neutralizing antibody against heterogeneous types of influenza virus, not only based on HA but also NA protective antigen, through convenient nasal immunization, which had non-inferiority titter compared with the chicken embryo-derived GYZZ02 vaccine on safe and effect. The Vero cell-derived vaccine (LAIV) combined compound catt adjuvant (contain carbopol971P and tetanus toxin) could provide another safety and protective program of influenza vaccine by intranasal administration, as catt-flu program., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Introduction: Limosilactobacillus reuteri effectively colonizing the gut, secretes antimicrobial compounds and strengthens immune system function. Considering these health benefits, increasing its stress assessments efficiency could improve its commercial viability., Methods: In this work, the resistance of L. reuteri FP41 to acid, bile salts, and freeze-drying was examined., Results: The findings showed that strain FP41 demonstrated a strong resistance to acid/bile salt stresses. The transcriptome revealed a significant up-regulation of various stress response genes, including those related to membrane integrity, glutamine metabolism, OsmC family protein, ABC transporters, and chaperonin. Subsequent research demonstrated that overexpression of three stress response-specific proteins, including glutamate decarboxylase GatD, osmotically induced bacterial protein OsmC, and membrane protein component CsbD, significantly increased the survival rate of L. reuteri Z204 under acid/bile salts stress. Notably, overexpression of the OsmC, CsbD, and GatD proteins also enhanced the survival of L. reuteri after freeze-drying., Discussion: The development of a unique cross-protection method is highlighted in this study, that might significantly increase cellular resistance to acid, bile salts, and cold stresses. This finding could significantly impact the way that L. reuteri is employed in industrial manufacturing processes., 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 Liu, Zhao and Bangash.)

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.)

Papaya ringspot virus (PRSV) is a catastrophic disease that causes huge yield losses in papaya cultivation around the world. Yield losses in severely infected plants can be upto 100%. Because of this disease, papaya cultivation has been shifted to other crops in some areas of the world. Many conventional methods and breeding approaches are used against this disease, which turns out to be less effective. Considering the yield loss caused by PRSV in papaya, it is high time to focus on alternative control methods. To implement effective management strategies, molecular approaches such as Marker Assisted Breeding (MAS) or transgenic methods involving post-transcriptional gene silencing targeting the genome viz., coat protein, replicase gene, or HC Pro can be pursued. However, the public's reluctance to widely accept the transgenic approach due to health and environmental concerns necessitates a consideration of non-transgenic alternatives. Prioritizing safety and ensuring efficient virus control, non-transgenic approaches which encompass cross-protection, genome editing, and topical applications of dsRNA to induce gene silencing within the host, can be adopted. This review aims to provide comprehensive insights of various molecular tools used in managing PRSV which in turn will help in sustainable agriculture., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Influenza seasons occur annually, building immune history for individuals, but the influence of this history on subsequent influenza vaccine protection remains unclear. We extracted data from an animal trial to study its potential impact. The trial involved 80 ferrets, each receiving either one type of infection or a placebo before vaccination. We quantified the vaccine protection by evaluating hemagglutination inhibition (HAI) antibody titer responses. We tested whether hosts with different infection histories exhibited similar level of responses when receiving the same vaccine for all homologous and heterologous outcomes. We observed that different pre-existing immunities were generally beneficial to vaccine induced responses, but varied in magnitude. Without pre-immunity, post-vaccination HAI titers after the 1st dose of the vaccine were less likely to be above 1:40, and a booster shot was needed. Our study suggests that pre-existing immunity may strengthen and extend the homologous and heterologous vaccine responses., 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.)

Pneumococcal vaccines are a cornerstone for the prevention of pneumococcal diseases, reducing morbidity and mortality in children and adults worldwide. Pneumococcal vaccine composition is based on the polysaccharide capsule of Streptococcus pneumoniae , which is one of the most important identified contributors to the pathogen's virulence. Similarities in the structural composition of polysaccharides included in licensed pneumococcal vaccines may result in cross-reactivity of immune response against closely related serotypes, including serotypes not included in the vaccine. Therefore, it is important to understand whether cross-reactive antibodies offer clinical protection against pneumococcal disease. This review explores available evidence of cross-reactivity and cross-protection associated with pneumococcal vaccines, the challenges associated with the assessment of cross-reactivity and cross-protection, and implications for vaccine design and development.

The Marburg virus (MARV), belonging to the Filoviridae family, poses a significant global health threat, emphasizing the urgency to develop Marburg virus-like particle (VLP) vaccines for outbreak mitigation. The virus's menacing traits accentuate the need for such vaccines, which can be addressed by VLPs that mimic its structure safely, potentially overcoming past limitations. Early Marburg vaccine endeavors and their challenges are examined in the historical perspectives section, followed by an exploration of VLPs as transformative tools, capable of eliciting immune responses without conventional risks. Noteworthy milestones and achievements in Marburg VLP vaccine development, seen through preclinical and clinical trials, indicate potential cross-protection. Ongoing challenges, encompassing durability, strain diversity, and equitable distribution, are addressed, with proposed innovations like novel adjuvant, mRNA technology, and structure-based design poised to enhance Marburg VLP vaccines. This review highlights the transformative potential of Marburg VLPs in countering the virus, showcasing global collaboration, regulatory roles, and health equity for a safer future through the harmonious interplay of science, regulation, and global efforts., Competing Interests: 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., (© 2024 The Authors.)

East Asian Passiflora virus (EAPV) causes passionfruit woodiness disease, a major threat limiting passionfruit production in eastern Asia, including Taiwan and Vietnam. In this study, an infectious cDNA clone of a Taiwanese severe isolate EAPV-TW was tagged with a green fluorescent protein (GFP) reporter to monitor the virus in plants. Nicotiana benthamiana and yellow passionfruit plants inoculated with the construct showed typical symptoms of EAPV-TW. Based on our previous studies on pathogenicity determinants of potyviral HC-Pros, a deletion of six amino acids (d6) alone and its association with a point mutation (F 8 I, simplified as I 8 ) were conducted in the N-terminal region of the HC-Pro gene of EAPV-TW to generate mutants of EAPV-d6 and EAPV-d6I 8 , respectively. The mutant EAPV-d6I 8 caused infection without conspicuous symptoms in N. benthamiana and yellow passionfruit plants, while EAPV-d6 still induced slight leaf mottling. EAPV-d6I 8 was stable after six passages under greenhouse conditions and displayed a zigzag pattern of virus accumulation, typical of a beneficial protective virus. The cross-protection effectiveness of EAPV-d6I 8 was evaluated in both N. benthamiana and yellow passionfruit plants under greenhouse conditions. EAPV-d6I 8 conferred complete cross-protection (100%) against the wild-type EAPV-TW-GFP in both N. benthamiana and yellow passionfruit plants, as verified by no severe symptoms, no fluorescent signals, and PCR-negative status for GFP. Furthermore, EAPV-d6I 8 also provided complete protection against Vietnam's severe strain EAPV-GL1 in yellow passionfruit plants. Our results indicate that the attenuated mutant EAPV-d6I 8 has great potential to control EAPV in Taiwan and Vietnam via cross-protection.

Frozen dough technology is important in modern bakery operations, facilitating the transportation of dough at low temperatures to downstream sales points. However, the freeze-thaw process imposes significant stress on baker's yeast, resulting in diminished viability and fermentation capacity. Understanding the mechanisms underlying freeze-thaw stress is essential for mitigating its adverse effects on yeast performance. This review delves into the intricate mechanisms underlying freeze-thaw stress, focusing specifically on Saccharomyces cerevisiae , the primary yeast used in baking, and presents a wide range of biotechnological approaches to enhance freeze-thaw resistance in S. cerevisiae . Strategies include manipulating intracellular metabolites, altering membrane composition, managing antioxidant defenses, mediating aquaporin expression, and employing adaptive evolutionary and breeding techniques. Addressing challenges and strategies associated with freeze-thaw stress, this review provides valuable insights for future research endeavors, aiming to enhance the freeze-thaw tolerance of baker's yeast and contribute to the advancement of bakery science., Competing Interests: Conflict of interestThe author reports no conflict of interest., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Current influenza vaccine is not effective in providing cross-protection against variants. We evaluated the immunogenicity and efficacy of multi-subtype neuraminidase (NA) and M2 ectodomain virus-like particle (m-cNA-M2e VLP) and chimeric M2e-H3 stalk protein vaccines (M2e-H3 stalk) in ferrets. Our results showed that ferrets with recombinant m-cNA-M2e VLP or M2e-H3 stalk vaccination induced multi-vaccine antigen specific IgG antibodies (M2e, H3 stalk, NA), NA inhibition, antibody-secreting cells, and IFN-γ secreting cell responses. Ferrets immunized with either m-cNA-M2e VLP or M2e-H3 stalk vaccine were protected from H1N1 and H3N2 influenza viruses by lowering viral titers in nasal washes, trachea, and lungs after challenge. Vaccinated ferret antisera conferred broad humoral immunity in naïve mice. Our findings provide evidence that immunity to M2e and HA-stalk or M2e plus multi-subtype NA proteins induces cross-protection in ferrets., 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 Inc. All rights reserved.)

The influenza vaccines currently approved for clinical use mainly include inactivated influenza virus vaccines and live attenuated influenza vaccines (LAIVs). LAIVs have multiple advantages, such as ease of use and strong immunogenicity, and can provide cross-protection. In this study, the M gene of the PR8 virus was mutated as follows (G11T, C79G, G82C, C85G, and C1016A), and a live attenuated influenza virus containing the mutated M gene was rescued and obtained using reverse genetic technology as a vaccine candidate. The replication ability of the rescued virus was significantly weakened in both MDCK cells and mice with attenuated virulence. Studies on immunogenicity found that 1000 TCID 50 of mutated PR8 (mPR8) can prime strong humoral and cellular immune responses. Single-dose immunization of 1000 TCID 50 mPR8 was not only able to counter the challenge of the homologous PR8 virus but also provided cross-protection against the heterologous H9N2 virus.

Convalescent plasma has been shown to be effective at protecting humans against severe diseases caused by New World (NW) arenaviruses, including Junin virus (JUNV) and Machupo virus (MACV). This plasma contains antibodies against the full complement of structural proteins including the nucleocapsid and envelope glycoproteins (GPcs) consisting of GP1 and GP2. To gain insights into the protective and cross-protective properties of anti-GPc-specific polyclonal antibodies, we evaluated the ability of a DNA vaccine-produced anti-GPc rabbit antisera targeting MACV strain Carvallo to provide heterologous protection against another MACV strain termed Chicava in the Hartley guinea pig model. The neutralizing activity of the rabbit antisera against the heterologous MACV strains Chicava and Mallale was found to be 54-fold and 23-fold lower, respectively, compared to the titer against the homologous MACV strain Carvallo in the PRNT50 assay. Despite lower neutralizing activity against the strain Chicava, the rabbit antisera protected 100% of the guinea pigs from this strain when administered up to four days post-infection, whereas all the control animals succumbed to the disease. Using vesicular stomatitis virus (VSV) particles pseudotyped with MACV GPc, we identified a single amino acid difference at position 122 between the strains Chicava and Carvallo GPc that significantly influenced the neutralization activity of the rabbit antisera. These findings indicate that polyclonal antibodies targeting the MACV glycoproteins can protect against lethal infection in a post-challenge setting. These data will help guide future antibody-based therapeutics development against NW arenaviruses.

Tobacco (Nicotiana tabacum) is one of the major cash crops in China. Potato virus Y (PVY), a representative member of the genus Potyvirus, greatly reduces the quality and yield of tobacco leaves by inducing veinal necrosis. Mild strain-mediated cross-protection is an attractive method of controlling diseases caused by PVY. Currently, there is a lack of effective and stable attenuated PVY mutants. Potyviral helper component-protease (HC-Pro) is a likely target for the development of mild strains. Our previous studies showed that the residues lysine at positions 124 and 182 (K 124 and K 182 ) in HC-Pro were involved in PVY virulence, and the conserved KITC motif in HC-Pro was involved in aphid transmission. In this study, to improve the stability of PVY mild strains, K at position 50 (K 50 ) in KITC motif, K 124 , and K 182 were separately substituted with glutamic acid (E), leucine (L), and arginine (R), resulting in a triple-mutant PVY-HC ELR . The mutant PVY-HC ELR had attenuated virulence and did not induce leaf veinal necrosis symptoms in tobacco plants and could not be transmitted by Myzus persicae. Furthermore, PVY-HC ELR mutant was genetically stable after six serial passages, and only caused mild mosaic symptoms in tobacco plants even at 90 days post inoculation. The tobacco plants cross-protected by PVY-HC ELR mutant showed high resistance to the wild-type PVY. This study showed that PVY-HC ELR mutant was a promising mild mutant for cross-protection to control PVY., 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.)