Immunogen selection and prior #immunity shape #antibody breadth following immunisation with avian #H5 #hemagglutinin

 

Abstract

Avian influenza A viruses pose a persistent zoonotic threat to humans owing to their expanding host range and high case fatality rates. In particular, viruses from the 2.3.4.4b clade of the H5 subtype have now been detected in over 60 mammalian species, raising serious pandemic concerns. Understanding immune recognition of the H5 hemagglutinin (HA) is therefore critical for effective vaccine design and pandemic preparedness. To understand the breadth of cross-recognition induced by different H5 strains, we selected genetically diverse H5 human isolates from 2003-2023 and assessed neutralising antibody responses elicited by adjuvanted recombinant HA protein-based vaccines in C57BL/6 mice. Neutralisation activity of sera was determined against seven H5 HA variants using pseudotyped viruses and a PR8-reassortant virus in micro-neutralisation assays. Our results showed a wide variety of cross-strain neutralisation across H5 HA antigen variants. The conventional vaccine strain A/Indonesia/05/2005 displayed narrow activity against emerging clade 2.3.4.4b viruses, whereas ancestral variants exhibited cross-neutralisation profiles showing a diversity of breath but with limited potency. Polyvalent H5 HA formulations and nanoparticle-displayed H5 HA platforms substantially broadened cross-neutralisation against diverse H5 strains. To examine the impact of pre-existing immunity on H5 vaccine immunogenicity in mouse models, mice were primed with either seasonal influenza infection or quadrivalent influenza vaccine (QIV) prior to H5 HA immunisation. QIV pre-vaccination, but not prior influenza infection, enhanced subsequent neutralizing responses towards A/Fujian-Sanyuan/21099/2017 (clade 2.3.4.4b) H5. Collectively, our results demonstrate that immunogen selection and prior immunity shape antibody breadth following immunisation with avian A(H5) hemagglutinin.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.09.01.748495v1

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#Bundibugyo virus #glycoprotein seroreactivity following recombinant VSV–Zaire #Ebola virus glycoprotein #vaccination in outbreak-affected populations of #DRC: a longitudinal cohort study

 

Summary

Background

There are currently no licensed vaccines for disease caused by Bundibugyo virus (BDBV). The recombinant vesicular stomatitis virus–Zaire Ebola virus glycoprotein (rVSVΔG-ZEBOV-GP) vaccine has been widely deployed during Ebola virus disease outbreaks caused by Ebola virus (EBOV). Human studies have shown cross-reactive BDBV antibody responses following licensed Ebola virus disease vaccine administration, but the durability and longitudinal kinetics of these responses in populations vaccinated during outbreaks remain unknown. We aimed to evaluate BDBV glycoprotein seroreactivity following rVSVΔG-ZEBOV-GP vaccination in two longitudinal cohorts from regions of the Democratic Republic of the Congo affected by Ebola virus disease outbreaks.

Methods

This longitudinal cohort study was done in Mbandaka, Equateur Province, and Beni, North Kivu Province. Individuals aged 1 year and older who received the rVSVΔG-ZEBOV-GP vaccine under the WHO ring-vaccination protocol were eligible for enrolment. These populations were defined as: people with confirmed Ebola virus disease, contacts of people with Ebola virus disease or contacts-of-contacts, and health-care or front-line workers in areas affected by Ebola virus disease. Participants were enrolled from June 2 to July 3, 2018, in Mbandaka and from Aug 15 to 29, 2018, in Beni. Serum samples were collected from vaccine recipients and antibody reactivity was assessed using a multiplex pan-filovirus immunoassay. Both cohorts were followed up over 5 years, with seven data collection periods in each province. We evaluated longitudinal trends in EBOV and BDBV glycoprotein seroreactivity using a pan-filovirus multiplex immunoassay across follow-up visits.

Findings

We analysed 5849 serum samples from 1081 participants. 715 (66%) of 1081 participants were male and 366 (34%) were female. BDBV glycoprotein seroreactivity differed substantially between study sites. At baseline, 16 (3%) of 482 participants in Mbandaka and 62 (10%) of 599 in Beni were seroreactive to BDBV glycoprotein. In Mbandaka, BDBV glycoprotein antibody reactivity remained stable through to 6 months after initial vaccination before increasing from a mean median fluorescent intensity (MFI) of 1238 (SD 1599) at 2·5 years, with 16 (5%) of 355 seroreactive, to 4845 (5881) at 3·5 years and 116 (35%) of 329 seroreactive (p<0·0001), followed by waning at later visits. In Beni, BDBV glycoprotein antibody reactivity increased rapidly after the initial vaccination, with seroreactivity peaking at 21 days to a mean MFI of 6678 (SD 6997) with 283 (52%) of 541 participants seroreactive and at 6 months to an MFI of 6852 (6560) with 270 (54%) of 501 seroreactive. Although antibody levels decreased after 6 months, EBOV glycoprotein and BDBV glycoprotein antibody reactivity remained above baseline through to 5 years after vaccination.

Interpretation

The differing patterns of BDBV glycoprotein seroreactivity observed between Beni and Mbandaka warrant further investigation into the epidemiological and immunological factors associated with this seroreactivity, including the epidemiological significance of baseline seroreactivity observed before vaccination. To our knowledge, these findings provide the first longitudinal human data describing BDBV glycoprotein seroreactivity following licensed Ebola virus disease vaccination in populations living in regions now affected by the current outbreak of disease caused by BDBV. They add to the growing body of human evidence describing cross-reactive antibody responses following licensed Ebola virus disease vaccination and support rigorous clinical evaluation of rVSVΔG-ZEBOV-GP during the ongoing outbreak while BDBV-specific vaccines continue to be developed.

Funding

The US Food and Drug Administration, the Gates Foundation, and the US Defense Advanced Research Projects Agency.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S0140673626016089?dgcid=rss_sd_all

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Transcriptomic and proteomic signatures following #AS03-adjuvanted #Influenza #H7N9 #vaccine

 

Abstract

Introduction: 

Vaccines targeting avian influenza virus A/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood.

Methods: 

We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal influenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that.

Results: 

AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood.

Discussion: 

Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness.

Clinical Trial Registration: https://clinicaltrials.gov/study/NCT02921997?term=NCT02921997&viewType, idientifier NCT02921997.

Source: 

Link: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1786231/full

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#WHO and #Africa CDC welcome the allocation of #Ebola #vaccines to the #DRC (WHO, August 20 '26)

 

    Last week, the government of the Democratic Republic of the Congo (DRC) requested a release of Ervebo vaccines from the global Ebola virus disease vaccine stockpile, managed by the International Coordinating Group on Vaccine Provision (ICG). 

    The request was for use of the vaccine in the current Bundibugyo virus disease outbreak. 

    Ervebo vaccine is licensed and recommended for use in outbreaks of Ebola virus disease (previously called Zaire ebolavirus). 

    On Monday, the ICG informed the DRC government of an immediate initial release of 70 000 doses.

    The allocation includes 20 000 doses for a Phase 3 clinical trial to understand the impact of the vaccine on the Bundibugyo virus, and 50 000 doses for frontline and health workers in line with the current recommendations of the WHO Strategic Advisory Group of Experts on Immunization (SAGE).

    It is not known whether Ervebo may be protective against the Bundibugyo virus in humans. 

    Early laboratory and animal data suggest it may provide some protection. Thus, the clinical trial is expected to provide important new evidence, which is essential for policy-makers to inform future use of the Ervebo vaccine. It is key that the people offered the vaccine, in the trial and otherwise, receive information of the risks, potential benefits and limitations related to the use of the vaccine in an outbreak of Bundibugyo virus and are able to provide informed consent. 

    The ICG partners are WHO, the International Federation of the Red Cross and Red Crescent Societies, Médecins Sans Frontières and UNICEF. Gavi, the Vaccine Alliance, provides funding for the stockpile.

    WHO and the Africa Centres for Disease Control and Prevention (Africa CDC) welcome the allocation of vaccines to the DRC. 

    Against the backdrop of the ongoing outbreak, and based on the available evidence, WHO and Africa CDC support DRC's focus on protecting the people of DRC and using a community-led approach, which empowers communities to play a central role in the response.

    Africa CDC and WHO are united in support of the Government of the DRC, to protect affected communities, save lives and bring the Bundibugyo Ebola outbreak to an end, while generating the scientific evidence needed to strengthen Africa's preparedness for future outbreaks.

Note to editors

    The International Coordinating Group (ICG) on Vaccine Provision was established in 1997, following major outbreaks of meningitis in Africa, as a mechanism to manage and coordinate the provision of emergency vaccine supplies and antibiotics to countries during major outbreaks. 

    The partners and founding institutions are the International Federation of the Red Cross and Red Crescent Societies, MSF, UNICEF and WHO. 

    The core mandate of the ICG is to make available and ensure equitable access to licensed vaccines for cholera, meningitis, yellow fever, and Ebola virus disease during outbreaks. 

    Ebola vaccine stockpile: 

        The ICG has managed the emergency stockpile of Ebola vaccine since January 2021, which was created as an additional tool to control outbreaks of Ebola virus (previously called Zaire ebolavirus). 

        Since the establishment of ICG Ebola mechanism in 2021 until July 2026, over 56 000 doses of Ervebo vaccine have been allocated to respond to Ebola virus outbreaks in DRC. 

        A further 167 000 doses have been used in preventive campaigns for health and frontline workers in DRC, Guinea-Bissau, Kenya, Sierra Leone and Uganda.

Source: 

Link: https://www.who.int/news/item/20-08-2026-who-and-africa-cdc-welcome-the-allocation-of-ebola-vaccines-to-the-democratic-republic-of-the-congo

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The return of #H1N1: Reemergence of the #influenza virus A subtype H1N1 in 1977

 

Abstract

Four major influenza pandemics and two notable outbreaks have been recorded since 1900. This paper discusses the history of the 1977 influenza virus A H1N1 outbreak and re-emergence, often referred to as the “Russian flu” or the “red flu". We describe the likely events leading to the outbreak, including a brief history of the 1976 H1N1 outbreak in a military base in the United States. We reconstruct the spread of the H1N1 virus across the globe in 1977–1978 and discuss the epidemiology of the outbreak. We describe the likely origins of this unusual outbreak mainly affecting young people, including opinions and evidence pointing towards an unnatural origin. Finally, we outline the vaccines developed and vaccination campaigns that were carried out to combat the outbreak.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S0264410X26007723?via%3Dihub

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A novel candidate #vaccine virus derived from #Japan's first #mammalian case of clade 2.3.4.4b #H5N1 highly pathogenic avian #influenza virus

 

Abstract

The development of candidate vaccine viruses (CVVs) for pre-pandemic preparedness requires attenuation of pathogenicity while maintaining immunogenicity. In this study, we developed and characterized NIID-002, a reassortant virus derived from A/Ezo red fox/Hokkaido/1/2022 (H5N1; clade 2.3.4.4b), to evaluate its suitability as a candidate vaccine. NIID-002 exhibited markedly reduced pathogenicity compared with its parental strain, while retaining broad antigenic reactivity and protein yield comparable to other clade 2.3.4.4b CVVs. In mammalian models, NIID-002 demonstrated strong attenuation, causing no lethal infection in mice and only minimal weight loss with limited viral replication in ferrets. Antisera raised against NIID-002 reacted broadly with recent wild-type H5N1 isolates, suggesting potential broad protection. Protein yield analysis confirmed a production efficiency comparable to that of other CVVs within the same clade, supporting its feasibility for large-scale vaccine manufacturing. Overall, NIID-002 fulfills the key requirements for the pandemic preparedness of CVV, combining reduced pathogenicity, broad antigenic reactivity, and adequate production efficiency. These findings highlight its potential as a candidate H5N1 vaccine and underscore the continued need for surveillance and refinement of influenza vaccine strategies to address evolving viral threats.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26008571?via%3Dihub

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High rates of #SARS-CoV-2 #reinfection in residents of long term care facilities despite robust #spike-specific #immunity following serial #vaccination

 

Abstract

Older adult residents of long-term care facilities (LTCFs) suffered high rates of mortality during the initial stages of the COVID-19 pandemic but their clinical risk has decreased markedly following vaccination. Here we determined humoral and cellular immunity following delivery of a 5th vaccine dose, an mRNA spike B1:BA.1 bivalent vaccine, to care home residents. The delivery of a 5th vaccine elicited a plateau of spike-specific immunity that remained broadly stable over 100 days in almost all people. Despite this, 15% of residents had a primary infection and 30% became reinfected during 6-months of follow up. These findings reveal that serial vaccine delivery can establish robust systemic spike-specific immune responses in frail older people but that this does not reliably prevent SARS-CoV-2 reinfection. As such, additional approaches should be considered to reduce reinfection risk in this vulnerable population group.

Source: 

Link: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354079

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#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.

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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.

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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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