Single immunization with an influenza hemagglutinin nanoparticle‐based vaccine elicits durable protective immunity

Author:

Chiba Shiho12,Maemura Tadashi1,Loeffler Kathryn3,Frey Steven J.3,Gu Chunyang1,Biswas Asim1ORCID,Hatta Masato1,Kawaoka Yoshihiro1245,Kane Ravi S.3ORCID

Affiliation:

1. Department of Pathobiological Sciences, School of Veterinary Medicine Influenza Research Institute, University of Wisconsin‐Madison Madison Wisconsin USA

2. Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA) The University of Tokyo Tokyo Japan

3. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology Atlanta Georgia USA

4. Division of Virology, Department of Microbiology and Immunology Institute of Medical Science, University of Tokyo Tokyo Japan

5. The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute Tokyo Japan

Abstract

AbstractVaccination is the most effective strategy to combat influenza. Ideally, potent and persistent vaccine effects would be induced with a single vaccine dose. Here, we designed a virus‐like particle (VLP)‐based vaccine presenting multiple copies of the influenza hemagglutinin (HA) from A/Puerto Rico/8/1934 (PR8HA‐VLP) and examined its immunogenicity and protective efficacy in ferrets. Serum‐neutralizing antibodies were effectively induced against the homologous virus at 3‐week post‐vaccination with a single dose of PR8HA‐VLP with or without adjuvants. When the single‐immunized ferrets were challenged with the homologous virus, virus replication in the nasal mucosa was significantly reduced. Long‐term monitoring of serum titers revealed that after adjuvanted vaccination with PR8HA‐VLP, neutralizing antibodies were retained at similar levels 20‐ to 183‐week post‐vaccination, although a 4‐ to 8‐fold titer decline was observed from 3‐ to 20‐week post‐vaccination. Boost immunization at 183 weeks after the first immunization elicited higher neutralizing antibody titers than those at 3 weeks after the initial immunization in most of the animals. These results confirm that nanoparticle‐based vaccines are a promising approach to effectively elicit durable multiyear neutralizing antibody responses against influenza viruses.

Funder

National Institutes of Health

Japan Agency for Medical Research and Development

National Science Foundation

Bill and Melinda Gates Foundation

Publisher

Wiley

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