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Open AccessArticle

Historical H1N1 Influenza Virus Imprinting Increases Vaccine Protection by Influencing the Activity and Sustained Production of Antibodies Elicited at Vaccination in Ferrets

1
Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada
2
Center for Vaccines and Immunology, Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA
3
Department of Pediatrics, Division of Infectious Disease, Faculty of Medicine, Dalhousie University, Halifax, NS B3K 6R8, Canada
4
Canadian Centre for Vaccinology, IWK Health Centre, Halifax, NS B3K 6R8, Canada
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(4), 133; https://doi.org/10.3390/vaccines7040133
Received: 19 July 2019 / Revised: 18 September 2019 / Accepted: 23 September 2019 / Published: 28 September 2019
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year and subsequently build a complex influenza virus immune history. Despite this knowledge, little is known about how the imprinting strain influences vaccine responses. To investigate the immune responses of the imprinted host to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60-day recovery period to build immune memory, ferrets were immunized and then challenged on Day 123. Antibody specificity and recall were investigated throughout the time course. At challenge, the imprinted vaccinated ferrets did not experience significant disease, while naïve-vaccinated ferrets had significant weight loss. Haemagglutination inhibition assays showed that imprinted ferrets had a more robust antibody response post vaccination and increased virus neutralization activity. Imprinted-vaccinated animals had increased virus-specific IgG antibodies compared to the other experimental groups, suggesting B-cell maturity and plasticity at vaccination. These results should be considered when designing the next generation of influenza vaccines. View Full-Text
Keywords: influenza virus; imprinting; Haemagglutinin; antibody titer; quadrivalent vaccine; influenza A; H1N1; split-virion; isotype; virus neutralization influenza virus; imprinting; Haemagglutinin; antibody titer; quadrivalent vaccine; influenza A; H1N1; split-virion; isotype; virus neutralization
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Francis, M.E.; McNeil, M.; Dawe, N.J.; Foley, M.K.; King, M.L.; Ross, T.M.; Kelvin, A.A. Historical H1N1 Influenza Virus Imprinting Increases Vaccine Protection by Influencing the Activity and Sustained Production of Antibodies Elicited at Vaccination in Ferrets. Vaccines 2019, 7, 133.

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