#Vaccine #imprinting drives increased #SARS-CoV-2 #variant infection in #children

 

Abstract

Virus exposure history, particularly first exposure, is believed to shape vaccine efficacy and infection susceptibility; however, evidence for mechanistic links between immune responses in individuals and epidemiological outcome in populations is scarce. Recent co-circulation of SARS-CoV-2 variants XFG and BA.3.2 has revealed a striking enrichment in BA.3.2 cases among children. By combining epidemiological modeling, serology and monoclonal antibody analysis in children and adults, we show the dependence of effective variant-specific antibodies on vaccination history which may explain birth-year influence on differential susceptibility to these co-circulating variants. Ancestral cross-reactive site I antibodies frequently neutralize BA.3.2, but not XFG. By contrast, Omicron type-specific site I/III and III antibodies frequently neutralize XFG but not BA.3.2, revealing a tradeoff in the ability to neutralize these two co-circulating strains. These findings mechanistically link immune history, variant neutralization, antibody repertoire and variant infection risk, and suggest that vaccination regimens in children should prioritize neutralization breadth.

Competing Interest Statement

E.J.W. advises Arpelos Bioscience, Arsenal Biosciences, Coherus, Danger Bio, IpiNovyx, New Limit, Marengo, Pluto Immunotherapeutics Related Sciences, Santa Ana Bio, and Synthekine. E.J.W. is a founder of and holds shares of Coherus, Danger Bio, and Arsenal Biosciences. All other authors declare no competing interests.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, https://ror.org/043z4tv69, 75N93021C00015, U19AI082630, AI105343, AI108545, AI155577, AI149680

National Cancer Institute, 75N91019D00024, 75N91022F00005, 75N91023F00016

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.12.739589v1

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Protective Efficacy Evaluation of Various Inactivated #Vaccines Against the Newly Circulated Highly Pathogenic Avian #Influenza Virus #H5N1 of Clade 2.3.4.4b in Pekin #Ducks

 

Abstract

Highly pathogenic avian influenza (HPAI) virus H5N1of clade 2.3.4.4b has emerged as the predominant lineage circulating in poultry flocks worldwide, raising concerns regarding the protective efficacy of currently available commercial vaccines, particularly in domestic ducks, which play an important role in virus maintenance and transmission. Thus, this study evaluated the immunogenicity along with the protective efficacy of four inactivated H5 vaccines against a recently isolated local HPAI-H5N1 (Newvalley-3-H5N1-2024, clade 2.3.4.4b) strain in Pekin ducks in Egypt. A total of 150 seronegative ducks were divided into vaccinated and control groups (10 groups) and vaccinated at 10 days of age. At 31 days of age, the vaccinated and positive control groups were challenged using 106.5 EID50/0.5 mL/duck with the local isolate (Newvalley-3-H5N1-2024) via the oculo-nasal route. The vaccine efficacy was assessed through clinical signs, survival rate, hemagglutination inhibition (HI) antibody titer, tracheal and cloacal viral shedding quantified by real-time RT-PCR, and histopathological examination of trachea, lung, pancreas, and brain tissues. Generally, all ducks vaccinated with the ValleyVac Avian Flu H5 plus and MEFLUVACTM H5 PLUS 8 showed a significantly higher survival rate (100%) at 10 days post-vaccination (DPV) than those in the positive control (66.7% mortality rate). In contrast, ducks exhibited mortality rates ranging from 6.7% in the SERVAC Flu H5N1 group to 13.4% in the Sinder Fluvac group. The ValleyVac Avian Flu H5 plus and MEFLUVAC™ H5 PLUS 8 vaccines induced the highest HI antibody titers at 7, 14, 21, and 28 DPV in both homologous and heterologous AIV antigens, resulting in a significant reduction in viral load among all vaccinated duck groups (p-value < 0.05) comparable to the positive control group. Conversely, the SERVAC Flu H5N1 and Sinder Fluvac vaccines provided partial protection, suboptimal immunogenicity at different time points, and elevated viral shedding. Histopathological findings in ValleyVac Avian Flu H5 plus and MEFLUVAC™ H5 PLUS 8 vaccines exhibited mild tissue alterations following AIV challenge. Marked pathological lesions were observed in the SERVAC Flu H5N1 and Sinder Fluvac vaccinated groups. Among tested vaccines, both ValleyVac Avian Flu H5 plus and MEFLUVACTM H5 PLUS 8 showed the highest level of protective efficacy against the circulating AIV strain compared with other commercial vaccines. This study highlights the need for continuous molecular surveillance, antigenic matching, and regular updating of vaccine seed strains to ensure efficient HPAI control in Egypt.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/891

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Protective effect of #H5N8 stockpiled #vaccine against a virus genetically identical to a #human isolate of #bovine #H5N1 #influenza virus

 

Summary

Background

Since early 2024, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b have caused extensive outbreaks in dairy cattle in the United States, with spillover into mammalian species, including humans. A bovine-derived A(H5N1) virus isolated from a human case retains high pathogenicity and transmissibility in mammalian models, highlighting its pandemic potential. Stockpiled pre-pandemic influenza vaccines are intended to provide early protection before strain-matched vaccines are available; however, their protective efficacy against bovine A(H5N1) viruses has not been directly evaluated in vivo.

Methods

In this study, we assessed the protective efficacy of an AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8) clade 2.3.4.4b-based influenza vaccine stockpiled in Japan using mouse and ferret models. Vaccinated and unvaccinated animals were challenged with a virus genetically identical to a human isolate of bovine A(H5N1) virus. Neutralising antibody responses, viral replication in organs, and survival were evaluated.

Findings

Vaccination with the AS03-adjuvanted A(H5N8)-based stockpiled vaccine induced robust neutralising antibody responses in both animal models, significantly suppressed viral replication, and conferred complete protection against lethal challenge. In contrast, all unvaccinated mice and ferrets succumbed to infection. These findings demonstrate that the AS03-adjuvanted A(H5N8)-based stockpiled vaccine provides strong cross-protective efficacy against bovine A(H5N1) viruses.

Interpretation

An AS03-adjuvanted A(H5N8)-based vaccine stockpiled in Japan could serve as an immediate countermeasure against bovine A(H5N1) viruses during the early phase of a pandemic.

Funding

This work was supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP20wm0125002) and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP223fa627001) from the Japan Agency for Medical Research and Development.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00314-2/fulltext

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Heterologous prime-boost #vaccination against #H5 avian #influenza: Safety and immunogenicity of a MF59-adjuvanted, cell-culture derived #H5N6 vaccine

 

ABSTRACT

With increasing H5 avian influenza cases reported globally and the potential for pandemic emergence, induction of cross-reactive antibody responses may represent an important attribute of an effective vaccine. This phase 2 extension study evaluated immunogenicity and safety of MF59-adjuvanted, cell culture-derived H5N6 vaccine (aH5N6c) in adults primed with MF59-adjuvanted, cell culture-derived H5N1 vaccine (aH5N1c) and in unprimed adults. Adults previously primed with two doses of aH5N1c in the parent study V89_18 were randomized to receive two aH5N6c doses (Group 1) or one aH5N6c and one placebo (Group 2) 3 weeks apart. Unprimed adults received two aH5N6c doses (Group 3). Immunogenicity was assessed by hemagglutination inhibition (HI) and microneutralization (MN) assays against the priming (H5N1) and booster (H5N6) strains on Days 1, 8, 22, 43, and 202. Among 258 exposed participants, primed subjects (Groups 1 and 2) showed higher HI geometric mean titers against both strains than unprimed (Group 3) subjects, with MN responses similarly enhanced. Heterologous H5N1 responses were robust in primed subjects (Day 43 HI GMTs: 333–343; seroconversion rates >89%) but minimal in unprimed subjects, with responses persisting to Day 202. Solicited adverse events were mild or moderate, comparable between groups, and consistent with other MF59-adjuvanted pandemic vaccines; no vaccine-related serious adverse events occurred. Heterologous H5N6 booster vaccination in H5N1-primed adults elicited strong cross-reactive immunity against the priming strain, demonstrating long-lasting immune memory for at least 6 y and supporting heterologous prime-boost strategies for pandemic preparedness against emerging H5 outbreaks.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/21645515.2026.2712791

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A One-Shot Multivalent Live-Attenuated Candidate #Influenza #Vaccine against Divergent #Zoonotic #H5N1 Clades

 

Abstract

The continued emergence of genetically diverse high pathogenicity avian influenza (HPAI) H5N1 viruses with zoonotic potential highlights the urgent need for developing vaccines capable of providing broad protection against multiple circulating clades. Here, we developed a one-shot, multivalent, live-attenuated influenza vaccine (LAIV) based on the temperature-sensitive (ts), cold-adapted (ca), and attenuated (att) influenza A/Ann Arbor/6/1960 master donor virus (MDV) that incorporates the hemagglutinin (HA) and neuraminidase (NA) glycoproteins from representative clades 2.3.4.4b (A/Louisiana/12/2024), 2.3.2.1a (A/Victoria/149/2024), and 2.3.2.1e (A/Cambodia/2302009/2023) H5N1 viruses. A single intranasal (IN) immunization of C57BL/6 mice with the multivalent LAIV elicited robust humoral immune responses, with immune sera exhibiting broad cross-reactivity against antigens from all three H5N1 clades included in the vaccine. Following homologous viral challenge, vaccinated C57BL/6 mice were completely protected from disease, demonstrating the immunogenicity and protective efficacy of the multivalent LAIV. By simultaneously targeting antigenically distinct H5N1 lineages with pandemic potential, this strategy expands antigenic coverage within a single LAIV to confirm pan-H5N1 protection. Together, these findings support the development and implementation of this multivalent LAIV as a broadly protective pan-H5N1 LAIV for pandemic preparedness.

Competing Interest Statement

The A.G.-S. laboratory has received research support from Avimex, Dynavax, Pharmamar, and Accurius, outside of the reported work within the last three years. A.G.-S. has consulting agreements for the following companies involving cash and/or stock within the last three years: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, Avimex, Pagoda, Accurius, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Virofend, Prosetta and A.A.C.T., outside of the reported work. A.G.-S. has been an invited speaker in meeting events within the last three years organized by Seqirus, Novavax and Hipra. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The Icahn School of Medicine at Mount Sinai has licensed some of these inventions to Medimmune, Avimex, Leinco Technologies, Castlevax, Virofend, Kerafast, Cell Signaling, EMD Millipore, Genentech, Paratus and Nura Bio, and as a result receives financial compensation. Subject to Mount Sinai receiving such financial consideration, AG-S will receive a portion of that consideration pursuant to the terms of the Mount Sinai Intellectual Property Policy. All other authors declare no commercial or financial conflict of interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.02.742385v1

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#WHO #Position Paper on #COVID19 #vaccines– July 2026 (Weekly Epidemiological Record, August 2 '26, summary)

 

{Summary}

WHO Position Paper on COVID-19 vaccines– July 2026 

Introduction 

    In accordance with its mandate to provide normative guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers {1} on vaccines and combinations of vaccines against diseases that have an international public health impact. 

    These papers are concerned primarily with the use of vaccines in large scale vaccination programmes. 

    The position papers are intended for use by national public health officials and managers of immunization programmes. 

    They may also be of interest to vaccine advisory groups, international funding agencies, health professionals, researchers, the scientific media, vaccine manufacturers and the general public. 

    Recommendations on the use of vaccines against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were issued by the WHO Strategic Advisory Group of Experts (SAGE) on Immunization {2} at its meeting in March 2026 and endorsed by WHO thereafter. 

    Evidence presented at this meeting, as well as SAGE’s conflict of interest  assessment, can be accessed at www.who.int/news-room/events/detail/2026/03/09/default-calendar/strategic-advisorygroup-of-experts-on-immunization-march-2026. 

    The vaccine position papers are developed by the WHO SAGE Secretariat with input from WHO staff at the headquarters and regional levels. 

    The vaccine position papers summarize essential background information on diseases and vaccines and conclude with the current WHO position on the use of vaccines worldwide. 

    The position papers are reviewed by a large group of external subject-matter experts and end-users before finalization. 

    The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the evidence-to-decision tables are published alongside the position papers. 

    The methods followed by SAGE {3} and the processes {4} for preparation of vaccine position papers are described on the WHO website. 

    This position paper is concerned with vaccines and vaccination against COVID-19 and supersedes previous interim guidance issued by WHO on this subject. 

    Since the WHO declaration of the COVID-19 Public Health Emergency of International Concern (PHEIC) in early 2020, {5} WHO has issued a comprehensive set of strategic and guidance documents to support countries in planning, implementing, monitoring, optimizing and assessing the impact of COVID-19 vaccination. 

    These included the WHO SAGE values framework for the allocation and prioritization of COVID-19 vaccination; {6} successive roadmaps to prioritize vaccine use in response to evolving evidence, vaccine supply and epidemiological context; {7} vaccine product-specific and platform interim recommendations for the WHO Emergency Use Listing (EUL) and WHO prequalified COVID-19 vaccines; {8} COVID-19 vaccine delivery guidance, resources and tools; {9} and an overarching global COVID-19 vaccination strategy. {10,11} 

    In May 2023, WHO announced that COVID-19 no longer constituted a PHEIC due to decreasing trends in COVID-19 deaths and COVID-19-related hospitalizations and intensive care unit (ICU) admissions,  and the high levels of populationi mmunityto SARS-CoV-2.{12} 

    In December 2025, WHO published the Strategic plan for coronavirus disease threat management for the period 2025-2030,{13} which builds on and supersedes previous WHO strategic preparedness and response plans and provides the global framework for the sustained and integrated management of COVID-19 and other coronavirus diseases. 

    Recommendations in this position paper are provided in the context of Omicron and its sub-lineages being the predominant circulating SARSCoV-2 variant of concern with high population-level immunity to SARS-CoV-2 and the availability of mRNA and protein subunit COVID-19 vaccines. 

    The recommendations in this position paper will remain valid for new variant-adapted COVID19 vaccines. 

    They will be revised should new SARS-CoV-2 variants of concern arise, if there are significant changes in COVID-19 epidemiology, or if new evidence indicates that vaccine performance warrants modification of the policy recommendations.

(...)

___

{1} WHO Vaccine Position Papers. Geneva: World Health Organization (www.who.int/teams/immunization-vaccines-and-biologicals/policies/position-papers (http://www.who.int/teams/immunization-vaccines-and-biologicals/policies/position-papers)). 

{2} Strategic Advisory Group of Experts (SAGE) on Immunization. Geneva: World Health Organization (https://www.who.int/groups/strategic-advisory-groupof-experts-on-immunization). 

{3} Guidance for the development of evidence-based vaccine-related recommendations. Geneva: World Health Organization; 2017 (www.who.int/publications/m/item/guidance-for-the-development-of-evidence-based-vaccine-related-recommendations). 

{4} Supplement to WHO Vaccine Position Papers. Geneva: World Health Organization; 2020 (www.who.int/publications/m/item/who-position-paper-process). 

{5} Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019nCoV). Geneva: World Health Organization; 2020 (https://www.who.int/news/item/30-01-2020-statement-on-the-second-meeting-of-the-internationalhealth-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov). 

{6} WHO SAGE values framework for the allocation and prioritization of COVID-19 vaccination Geneva: World Health Organization; 2020 ((https://www.who.int/publications/i/item/who-sage-values-framework-for-the-allocation-and-prioritization-of-covid-19-vaccination). Licence: CC BY-NC-SA 3.0 IGO. 

{7} WHO SAGE Roadmap for prioritizing uses of COVID-19 vaccines. Geneva: World Health Organization; 2023 (https://www.who.int/publications/i/item/WHO-2019-nCoV-Vaccines-SAGE-Prioritization-2023.1). Licence: CC BY-NC-SA 3.0 IGO.

{8} COVID-19 vaccines technical documents Geneva: World Health Organization; 2025 (https://www.who.int/groups/strategic-advisory-group-of-experts-onimmunization/covid-19-materials). Licence: CC BY-NC-SA 3.0 IGO. 

{9} COVID-19 vaccine delivery toolkit. Geneva: World Health Organization; 2026 (https://www.who.int/tools/covid-19-vaccine-introduction-toolkit). 

{10} Strategy to Achieve Global Covid-19 Vaccination by mid-2022. Geneva: World Health Organization; 2021 (https://www.who.int/publications/m/item/strategy-to-achieve-global-covid-19-vaccination-by-mid-2022). 

{11} Global COVID-19 vaccination strategy in a changing world: July 2022 update. Geneva: World Health Organization; 2022 (https://www.who.int/publicatio ns/m/item/global-covid-19-vaccination-strategy-in-a-changing-world--july-2022-update). 

{12} Statement on the fifteenth meeting of the IHR (2005) Emergency Committee on the COVID-19 pandemic. Geneva: World Health Organization; 2023 (https://www.who.int/news/item/05-05-2023-statement-on-the-fifteenth-meeting-of-the-international-health-regulations-(2005)-emergency-committeeregarding-the-coronavirus-disease-(covid-19)-pandemic). 

{13} Strategic plan for coronavirus disease threat management: advancingintegration, sustainability, and equity, 2025–2030. Geneva: WorldHealthOrganization; 2025 (https://www.who.int/publications/i/item/9789240117662). Licence: CC BY-NC-SA 3.0 IGO.

(...)

Source: 

Link: https://www.who.int/publications/i/item/who-wer101-30-138-156

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#Thrombotic and #cerebrovascular events following #SARS-CoV-2 #vaccination: an umbrella #review of systematic reviews and meta-analyses

 

Abstract

Rare thrombotic and cerebrovascular events have been reported after SARS-CoV-2 vaccination, raising safety concerns. This umbrella review synthesizes evidence from 19 systematic reviews and meta-analyses examining thrombotic outcomes, including acute ischemic stroke and cerebral venous sinus thrombosis, across different vaccine platforms. Methodological quality was assessed using AMSTAR-2, and findings were synthesized by outcome and platform. Evidence consistently shows that thrombotic and cerebrovascular events following vaccination are rare. mRNA vaccines (BNT162b2, mRNA-1273) were not associated with increased risk beyond background population rates. Adenoviral vector vaccines (ChAdOx1 nCoV-19, Ad26.COV2.S) were linked to a rare syndrome of vaccine-induced immune thrombotic thrombocytopenia, most commonly presenting as cerebral venous sinus thrombosis in younger adults. Evidence for whole-virus vaccines was limited but did not indicate consistent safety concerns. Across all platforms, thrombotic risk was substantially lower than that from SARS-CoV-2 infection. Overall, vaccination benefits outweigh risks, highlighting the importance of ongoing surveillance and transparent communication.

Source: 

Link: https://www.nature.com/articles/s41541-026-01550-5

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Pre-existing and Cross-Reactive #Immunity to Avian #Influenza #H5N1 in #Humans: Implications for #Pandemic #Risk and Vaccine Strategies

 

Highlights

    ° Evidence of cross-reactive antibodies to H5N1 in humans.

    ° Seasonal influenza may induce partial H5N1 cross-protection.

    ° H5N1 clade 2.3.4.4b shows expanded host range and spread.

    ° Role of viral glycoproteins in immune cross-reactivity.

    ° Implications of baseline immunity for H5N1 pandemic risk.

Abstract

Due to the continuous evolution of Influenza A viruses (IAVs), novel strains with efficient human-to-human transmission may emerge and cause future pandemics. Among these, highly pathogenic avian influenza (HPAI) H5N1 remains a major concern because of its impact on wildlife, livestock, and human health. The widespread circulation of H5N1 clade 2.3.4.4b, detected in hundreds of bird species and numerous mammals worldwide, highlights important changes in viral ecology and transmission, increasing its zoonotic and pandemic potential. This review summarizes current evidence on cross-reactive and cross-protective immunity to H5N1 in humans, focusing primarily on humoral immune responses. We examine the presence of pre-existing H5N1-reactive antibodies in individuals without known exposure and discuss how previous seasonal influenza infection or vaccination may contribute to their development. Particular attention is given to antibodies targeting conserved regions of hemagglutinin (HA), especially the stalk domain, as well as neuraminidase (NA), which may provide heterosubtypic protection. We also evaluate the ability of seasonal influenza vaccines and infections to induce cross-reactive responses against H5N1 and their potential role in partial protection or immune priming. Finally, we review current and emerging H5N1 vaccination strategies, including adjuvanted and mRNA-based platforms, and identify priorities for surveillance, population immunity assessment, and the development of broadly protective influenza vaccines.

Source: 

Link: https://www.journalofinfection.com/article/S0163-4453(26)00148-9/fulltext

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#SARS-CoV-2 BA.3.2.2 is more evasive of #neutralisation by #plasma from young #children

 

{Excerpt}

(...)

These findings suggest that susceptibility to emerging SARS-CoV-2 variants could diverge across age groups with different exposure histories. Adults in the USA and other countries have accumulated broader immunity through repeated infection and vaccination across antigenically distinct lineages, starting with the ancestral strain, whereas younger children and infants possess narrower exposure histories that are largely shaped by recent variants. The continued surveillance of SARS-CoV-2 variants should consider age-stratified differences in immunity, to anticipate or explain disproportionate burden of infections in some populations. Furthermore, studies of potential age-specific vaccine formulations targeting different variants are warranted, to investigate whether age-specific target selection could lead to broader protection across subpopulations with known differences in their exposure histories and susceptibility to co-circulating variants.

(...)

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00349-X/fulltext?rss=yes

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Elicitation of #stem-directed #antibodies in rhesus #macaques by a conventional #hemagglutinin immunogen

 

Abstract

Because they can bind many strains of influenza, antibodies targeting the hemagglutinin (HA) stem have been attractive targets for vaccine development. Many monoclonal antibodies (mAbs) directed at the HA stem have been isolated from humans, and these mAbs have mediated broad protection in animal models. We describe here HA stem-directed mAbs isolated from rhesus macaques immunized with an "ordinary" H1 HA trimer. All immunized rhesus macaques developed high serum titers with broad reactivity to diverse H1N1 and H5N1 viruses, and 7 isolated mAbs strongly blocked canonical stem antibody CR6261 binding to H1. MAb DH726.1 robustly protected mice from lethal challenge with H1N1 and H5N1 viruses, and cryo-EM showed the binding footprint overlapped that of some human mAbs. These findings suggest that vaccination with the standard, trimeric HA immunogens may be sufficient to elicit stem antibodies at titers adequate to protect against zoonotic H5N1 influenza.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

NIH NIAID, Division of Microbiology and Infectious Diseases, P01-AI089618

NIH NIAID Division of AIDS, Center for HIV/AIDS Vaccine Immunology, U19-AI067854

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.16.738984v1

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Loss of #hemagglutination ability by #H3N2 #influenza A virus, subclade K.

 

Abstract

Seasonal human H3N2 influenza viruses, subclade K (J.2.4.1), have been the predominant influenza A viruses in the Northern hemisphere influenza season of 2025/2026. Since 2024, the vaccine virus A/Darwin/6/21 has emerged in different antigenic variants. Antigenic changes are frequently caused by amino acid substitutions near the hemagglutinin (HA) receptor-binding pocket, which can also affect receptor binding properties, such as hemagglutination. Hemagglutination is crucial for assessing antigenicity using the hemagglutination inhibition (HAI) assay, and a loss of binding to turkey erythrocytes could significantly hamper this process. In this study, we explored how substitutions in or around the HA receptor-binding site affect binding to glycans at the molecular level. We employed ELISA, glycan array, flow cytometry, hemagglutination assays, and tissue staining. Substitutions at positions 140, 192, and 223 establish clade J viruses that emerged in 2024. Computational analysis of HA in complex with an elongated glycan reveals that mutation F192 forms a CH-Pi interaction to stabilize the binding. Based on this background, substitutions in antigenic sites A and B within subclade K viruses exhibit a binding preference for elongated glycans, which are not displayed on turkey erythrocytes. Conversely, our previously established glyco-remodeled erythrocytes are efficiently bound by these subclade K H3N2 viruses and could support influenza surveillance and vaccine development.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

CSC fellowship, (202209120001)

National Institute of Allergy and Infectious Diseases, R01 AI165692

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.20.739523v1

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Multiorgan #Outcomes Following #BNT162b2 #mRNA #Vaccination vs #SARS-CoV-2 #Infection: A 30-Million-Person Real-World Cohort Analysis

 

Abstract

SARS-CoV-2 infection and BNT162b2 mRNA vaccination carry distinct cardiovascular risk profiles, yet direct comparative evidence across all immunological exposure groups and both sexes remains limited. Using the TriNetX Research Network (December 2020–December 2024), we stratified 30.3 million individuals into four mutually exclusive cohorts: uninfected/unvaccinated controls (G1), infected/unvaccinated (G2), vaccinated-only (G3), and hybrid immunity (G4). Fifty prespecified cardiovascular, cerebrovascular, and mortality outcomes were evaluated across four temporal windows (0–3, 3–6, 6–9, and >9 months) with analyses stratified by biological sex. SARS-CoV-2 infection was associated with 3- to 5-fold increases in cardiovascular events during the acute phase, including myocarditis (males: RR 4.44; females: RR 5.59) and all-cause mortality (males: RR 4.53), with risks persisting beyond nine months. BNT162b2 vaccination conferred 65-76% reductions in major adverse cardiovascular events (0–3 months). Post-infection vaccination (hybrid immunity) provided an additional 36–38% MACE reduction; males exhibited late pericarditis elevation beyond nine months. Completing the two-dose primary series maximally reduced mortality (by 77%) and myocarditis (by 62%) versus single dosing. In this US cohort, SARS-CoV-2 infection confers substantially greater and more sustained cardiovascular risk than BNT162b2 vaccination across all comparisons and both sexes, consistent with a favorable cardiovascular risk-benefit profile for vaccination.

Source: 

Link: https://www.nature.com/articles/s41541-026-01528-3

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Immune correlates of #risk for #SARS-CoV-2 #infection in #children: a prospective, community-based cohort study

 

Abstract

Few studies have characterized immune correlates of SARS-CoV-2 infection risk in children, particularly those with hybrid immunity from vaccination and prior infection. We conduct a prospective community-based cohort study of 1509 U.S. children (2022–2024), performing weekly SARS-CoV-2 PCR testing and measuring baseline binding and neutralizing antibody titers against multiple variants. Higher antibody levels, notably nucleocapsid-binding and Omicron-specific neutralizing antibodies, are significantly associated with reduced risk of SARS-CoV-2 infection after adjusting for age, recent infection, exposure settings, and temporal trends (adjusted hazard ratios ranging from 0.60 to 0.87 per positive unit difference in log10-fold antibody level (AU/mL)). Secondary analyses suggest these findings are robust to multiple stratifications of SARS-CoV-2 immune status, are relevant across different pediatric age groups, and appear to apply to both overall and symptomatic infection risk. Together, the results suggest that specific antibodies can predict relative infection risk in pediatric populations with diverse immune histories. Understanding these immune correlates may inform tailored vaccination strategies and risk assessments as SARS-CoV-2 continues to evolve.

Source: 

Link: https://www.nature.com/articles/s41467-026-74684-8

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#Safety and efficacy of #mRNA #vaccines: a mechanistic and public health perspective

 

Summary

mRNA vaccines represent a transformative advance in vaccinology, combining rapid development timelines, scalable manufacturing, and strong immunogenicity with a favourable safety profile. Global deployment of mRNA vaccines during the COVID-19 pandemic provided an unprecedented real-world evaluation of this platform, with billions of doses administered across diverse populations. In this Review, we critically examine the safety and efficacy of mRNA vaccines from mechanistic, preclinical, clinical, and public health perspectives. We outline the biological basis of mRNA vaccines, including their transient cytoplasmic expression, lack of genomic integration, and rapid clearance, distinguishing them clearly from other gene therapies. We synthesise evidence on vaccine components, manufacturing quality controls, and regulatory standards that underpin safety, alongside data from randomised trials, post-authorisation surveillance, and active pharmacovigilance systems. We also review real-world effectiveness across age groups, pregnancy, and populations that are immunocompromised, along with the effects on transmission. Last, we address public perception and vaccine confidence, and discuss implications for next-generation mRNA vaccines, including strategies to reduce reactogenicity, improve breadth and durability of immunity, enhance global access, and support sustainable public trust. Together, the accumulated evidence affirms mRNA vaccines as a safe, effective, and adaptable platform with enduring relevance for future infectious disease prevention and public health preparedness, and for the treatment of cancer and autoimmunity.

Source: 

Link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00512-X/abstract?rss=yes

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Immunoinformatics-Guided Design and In Silico Evaluation of a Multi-Epitope #Vaccine Against #Influenza A #H10N5 and #H3N2 Strains Based on HA and NA Proteins

 

Abstract

Influenza A viruses H3N2 and H10N5 represent, respectively, a persistently dominant seasonal pathogen and a newly documented zoonotic threat with the latter strain variants responsible for the first confirmed human fatality in January 2024, yet no vaccine platform currently addresses co-protection against both subtypes within a unified immunogen. We report here the immunoinformatics based vaccine design and multi-layered computational validation of a 419-amino-acid multi-epitope subunit vaccine construct targeting conserved hemagglutinin (HA) and neuraminidase (NA) antigens identified through multiple sequence alignment of the avian H10N5 (A/swine/Hubei/10/2008) and H3N2 human reference strain sequences to identify viral agents undergoing mammalian adaptations. Linear B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were predicted using ABCpred, BCEpred, BepiPred 2.0, NetMHCpan 2.1, and NetMHCpan 4.0, then filtered through VaxiJen 3.0, AllerTOP v2.1, and ToxinPred to retain only antigenic, non-allergenic, non-toxic candidates. The final construct, incorporating an avian β-defensin N-terminal adjuvant with GPGPG, AAY, and EAAAK linkers, exhibited a molecular weight of 43.9 kDa, instability index of 31.15, and SOLPro solubility probability of 0.763. Tertiary structure modeling via I-TASSER and GalaxyRefine achieved 84.4% Ramachandran-favored residues. Molecular docking against TLR3 and TLR7 yielded binding free energies of −16.1 and −16.8 kcal/mol with picomolar dissociation constants. Molecular dynamics simulations confirmed complex stability over extended trajectories. Furthermore, codon optimization produced a Codon Adaptation Index of 1.0 for E. coli K12 expression. In silico immune simulation demonstrated robust activation of humoral and cellular immunity including elevated IgG1, IgM, IFN-γ, IL-2, rapid NK cell expansion, and broad B-cell clonal diversity. These findings establish a computationally validated candidate capable of providing protection against influenza in multiple host organisms, warranting experimental advancement.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.03.736294v1

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Preclinical #immunogenicity of the #LP81-adapted BNT162b2 #COVID19 #vaccine

 

Abstract

SARS-CoV-2 evolution toward antigenically distinct lineages drives escape from host immunity. JN.1 lineage derivatives have recently dominated the global epidemiologic landscape. In preclinical models, an LP.8.1-adapted BNT162b2 vaccine elicited higher serum neutralizing antibody responses against contemporary, circulating JN.1 sublineages, including the epidemiologically dominant XFG lineage, as compared to JN.1 and KP.2 vaccines. These findings supported the selection of an LP.8.1-adapted vaccine for the composition of the 2025-26 COVID-19 vaccine formula.

Source: 

Link: https://www.nature.com/articles/s41541-026-01515-8

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Cross-neutralization of #SARS-CoV-2 #BA322 #lineage by #JN1 #mRNA #vaccine-induced immunity

 

Highlights (for review)

    • JN.1 mRNA vaccination elicits cross-neutralizing antibodies against BA.3.2.2.

    • BA.3.2.2 is antigenically isolated from all circulating JN.1-descendant variants.

    • Retention of wild-type F456 in BA.3.2.2 preserves class 1/2 antibody epitopes.

    • AZD3152/sipavibart retains potent neutralization against BA.3.2.2.

    • VYD222/pemivibart maintains broad neutralization activity across all variants tested.

Abstract

The SARS-CoV-2 BA.3.2.2 sublineage has emerged globally as the dominant branch of BA.3.2 by late 2025, yet its antigenic relationship with JN.1 vaccine-induced immunity remains unclear. We evaluated neutralizing antibody responses in 25 JN.1 mRNA vaccinees against eight variants, stratified by anti-nucleocapsid antibody serostatus. Post-vaccination titers increased significantly against all variants in both N antibody-negative and -positive groups. Cross-neutralization against BA.3.2.2 was detected in both groups despite lower titers compared to JN.1. Antigenic cartography revealed that BA.3.2.2 was antigenically isolated from all JN.1-descendant variants. AZD3152/sipavibart retained potent neutralization against BA.3.2.2 but completely lost activity against all F456L-harboring JN.1-descendant variants, while VYD222/pemivibart and SA55 maintained broad activity. Retention of wild-type F456 in BA.3.2.2 preserves class 1/2 antibody epitopes, providing a mechanistic basis for cross-neutralization and suggesting a potential therapeutic window for sipavibart should BA.3.2.2 expand globally, pending clinical confirmation.

Source: 

Link: https://www.ijidonline.com/article/S1201-9712(26)00589-8/fulltext

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#Vaccine #strategies and #development before and during the 1968 #H3N2 #influenza #pandemic

 

Abstract

Nearly 60 years ago, in 1968, the global population was confronted with the emerging pandemic influenza A virus (IAV) subtype H3N2 (1968 H3N2pdm). An estimate of up to two million fatalities have been linked to 1968 H3N2pdm, and the H3N2 subtype continues to circulate as seasonal IAV among humans until today. The last IAV pandemic dates back to the year 2009 but concerns about a new IAV pandemic in the near future are increasing. The global spread of H5N1 highly pathogenic avian influenza virus and its spill-over into new mammalian hosts, discovery of novel influenza A virus with zoonotic or even pandemic potential, as well as seasonal influenza viruses undergoing antigenic changes necessitate constant vigilance. Here, we highlight the proactive actions, precautionary measures and vaccination strategies used during the 1968 H3N2 IAV pandemic. Our review highlights the emergence and spread of 1968 H3N2pdm over the course of the pandemic, alongside a delineation of vaccine development before, during and after the 1968 pandemic. Updating these strategies in the context of new findings combined with our experiences during the coronavirus disease 2019 (COVID-19) pandemic is necessary to improve preparedness for the next pandemic. Influenza viruses with zoonotic potential will remain a constant threat to public health, and improving countermeasures and communication to the public is key to limit the pandemic ramifications.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26006869?via%3Dihub

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Mapping #SARS-CoV-2 #immunity after an #XBB.1.5 #booster by antigenic cartography of merged #human and hamster sera

 

Abstract

The ongoing evolution of SARS-CoV-2, particularly the emergence and rapid spread of new immune-evasive variants, continues to challenge the durability of vaccine-induced protection. Understanding how repeated variant exposures shape neutralizing antibody breadth is therefore essential for optimizing booster design. Here, we investigated polyclonal neutralizing antibody responses in individuals who received a bivalent (ancestral + BA.4/5) boost followed by an additional monovalent XBB.1.5 boost, with and without breakthrough infection, against a diverse panel of SARS-CoV-2 variants. To visualize human multi-exposure immunity in antigenic space via antibody landscapes, we extended our existing human sera-based antigenic map with hamster sera infected with more recent variants. The hamster sera allowed us to map BA.2.86 and JN.1 variants, which largely escape human single exposure sera. Our analysis of human multi-exposure sera revealed that the number and type of exposures significantly shaped antibody landscapes. The XBB.1.5 booster immunization notably increased neutralizing antibody titers across variants, elevating the height of the antibody landscape. However, titers against more recent Omicron variants, such as JN.1, were low despite booster administration. These findings highlight the dynamic nature of SARS-CoV-2 immunity and emphasize the need for continuous monitoring and adaptation of vaccine strategies to maintain effective protection against emerging variants.

Source: npj Vaccine, https://www.nature.com/npjvaccines/

Link: https://www.nature.com/articles/s41541-026-01516-7

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#COVID19 #vaccination induces cross-neutralisation of #sarbecoviruses related to #SARS-CoV-2

 

Abstract

The combined threats of future sarbecovirus zoonosis and continually emerging SARS-CoV-2 VOCs highlight the need to assess the breadth of existing SARS-CoV-2 vaccine-mediated protection. Here, we investigate a cohort of older individuals who received four COVID-19 vaccine doses, for potential cross-neutralisation against lentiviral particles bearing spikes from either Omicron VOCs or other sarbecoviruses. Despite recent fourth bivalent mRNA vaccine doses (encoding SARS-CoV-2 Wu-1 and Omicron spikes), neutralisation of Omicron lineage VOCs was reduced compared to Wu-1, consistent with an imprinted immune response. Similarly, particles bearing either SARS-CoV-1 or a SARS-CoV-1-related bat sarbecovirus spike were neutralised less efficiently than Wu-1. Unexpectedly, however, we observed that particles with spikes from two animal SARS-CoV-2-related viruses, BANAL-20-52 from bats and a pangolin CoV, were significantly more sensitive to serum neutralising antibodies than SARS-CoV-2 Wu-1 itself. These surprising findings suggest that vaccine-mediated adaptive immunity may provide efficient cross-neutralisation and potential protection against certain animal sarbecoviruses.

Source: npj Vaccines, https://www.nature.com/npjvaccines/

Link: https://www.nature.com/articles/s41541-026-01469-x

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