#Antibody profiles across #H5N1 and previously circulating viruses are highly dynamic and #age- and imprint- independent

 

Abstract

The increasing incidence of H5N1 influenza virus transmission from animal species to humans has heightened concerns about an imminent H5N1 pandemic. Prior studies using recombinant hemagglutinin and neuraminidase proteins have reported age-dependent cross-reactivity to H5N1, attributed to immune imprinting from an individual's first influenza virus exposure. However, whether this pattern holds when using whole inactivated virus (WIV), capturing antibodies against diverse viral proteins, and is stable over time remains unknown. We therefore aimed to determine whether H5N1 cross-reactivity of pre-existing antibodies to whole virus follows an age-dependent or imprinting-specific pattern, and whether this pattern is stable over a five-year period. To this end, we measured serum antibody levels in adolescents, adults and seniors by ELISA using whole inactivated H5N1 virus as antigen rather than purified proteins. Detectable, albeit generally low, levels of H5N1-reactive antibodies were present in most individuals, irrespective of age. Comparison of antibody levels against H5N1 with those to five historical influenza virus strains revealed a consistent positive correlation between H5N1-reactive antibodies and responses to the H1N1pdm09 strain A/California/7/2009 (CA), across all age groups. Using unbiased clustering of antibody titers against H5N1, CA, and the H3N2 strain A/Perth/16/2009 (PE), we identified seven distinct age-transcending antibody profiles. These profiles covered individuals with varying titers to all three included viruses but also identified individuals with high anti-CA levels, yet low anti-H5N1 levels and vice versa. Moreover, despite stable antibody levels over a five-year interval in the study population, individual antibody levels and profiles fluctuated considerably over this period. Taken together, our results confirm the presence of H5N1-reactive antibodies in human sera and their association with previously circulating strains. However, they also caution against inferring antibody levels against a new strain based solely on responses to antigenically related strains and highlight the limitations of extrapolating immune status from single timepoint measurements.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.08.26.26361396v1

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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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Overcoming immune #imprinting with the #COVID19 #LP81 #mRNA #boosters

 

{Summary}

In summer 2025, the SARS-CoV-2 JN.1 sublineage became dominant with more resistant variants, such as XFG, LP.8.1, and NB.1.8.1. COVID-19 mRNA boosters were therefore updated for the 2025–2026 season to target the LP.8.1 spike.1 Previous boosters, particularly the WA1/2020+BA.5 bivalent booster, were characterised by substantial boosting of the ancestral strain, a phenomenon known as immune imprinting.2,3 We therefore evaluated whether the phylogenetically more distant LP.8.1 mRNA booster would preferentially boost currently circulating strains. Recent data from European and Asian populations have reported the immunogenicity of the LP.8.1 mRNA booster.4,5 Herein, we report the immunogenicity of the LP.8.1 mRNA booster in a US population with a different exposure history and high population immunity. We show that the LP.8.1 mRNA booster induced neutralising antibody (NAb) and binding antibody responses, primarily to the vaccine-matched L.P.8.1 variant and other currently circulating variants and lower responses to the ancestral WA1/2020 strain.

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Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00050-2/fulltext?rss=yes

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