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<p>Seasonal influenza viruses evade immunity through antigenic drift, enabling escape from inhibitory antibodies targeting hemagglutinin (HA) and neuraminidase (NA). In this study, we evaluated a non-propagating vesicular stomatitis virus (VSV) vector encoding HA and NA antigens of A/Hamburg/4/2009 (H1N1) in a porcine animal model to assess induction of cross-reactive immunity. A single intramuscular immunization elicited high titers of H1N1-neutralizing antibodies and potent N1-sialidase inhibition. A boost with the same single-cycle VSV-vectored H1/N1 antigens or with a live-attenuated influenza vaccine (LAIV) enhanced inhibitory activity against the antigen-drifted A/Victoria/2570/2019 (H1N1) strain. Vaccination induced N1-specific antibodies that also inhibited avian N1 sialidase and suppressed replication of a bovine-derived H5N1 virus in vitro. Following nasal challenge with a 6:2 reassortant virus encoding drifted HA and NA antigens, vaccinated pigs showed no detectable virus shedding, whereas control animals shed infectious virus. Homologous prime-boost vaccination with the VSV-vectored H1/N1 antigens conferred protection comparable to the heterologous VSV/LAIV regimen in the upper respiratory tract. These findings demonstrate that a single-cycle VSV vector encoding both HA and NA induces cross-protective immunity against antigen-drifted influenza viruses, reduces the risk of vaccine mismatch, and may limit infection by zoonotic H5N1 viruses.</p>

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Non-propagating RNA virus-vectored HA/NA vaccine prevents shedding of antigen-drifted H1N1 influenza virus in pigs

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月28日

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  • Obdulio García-Nicolás,
  • Lisa Butticaz,
  • Robin Avanthay,
  • Nicolas Ruggli,
  • Artur Summerfield,
  • Gert Zimmer

摘要

Seasonal influenza viruses evade immunity through antigenic drift, enabling escape from inhibitory antibodies targeting hemagglutinin (HA) and neuraminidase (NA). In this study, we evaluated a non-propagating vesicular stomatitis virus (VSV) vector encoding HA and NA antigens of A/Hamburg/4/2009 (H1N1) in a porcine animal model to assess induction of cross-reactive immunity. A single intramuscular immunization elicited high titers of H1N1-neutralizing antibodies and potent N1-sialidase inhibition. A boost with the same single-cycle VSV-vectored H1/N1 antigens or with a live-attenuated influenza vaccine (LAIV) enhanced inhibitory activity against the antigen-drifted A/Victoria/2570/2019 (H1N1) strain. Vaccination induced N1-specific antibodies that also inhibited avian N1 sialidase and suppressed replication of a bovine-derived H5N1 virus in vitro. Following nasal challenge with a 6:2 reassortant virus encoding drifted HA and NA antigens, vaccinated pigs showed no detectable virus shedding, whereas control animals shed infectious virus. Homologous prime-boost vaccination with the VSV-vectored H1/N1 antigens conferred protection comparable to the heterologous VSV/LAIV regimen in the upper respiratory tract. These findings demonstrate that a single-cycle VSV vector encoding both HA and NA induces cross-protective immunity against antigen-drifted influenza viruses, reduces the risk of vaccine mismatch, and may limit infection by zoonotic H5N1 viruses.