Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Historical H1N1 Influenza Virus Imprinting Increases Vaccination Efficacy by Influencing Antibody Longevity and Neutralization Activity in Ferrets

Version 1 : Received: 19 July 2019 / Approved: 23 July 2019 / Online: 23 July 2019 (04:03:13 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Abstract

Influenza virus imprinting is now understood to significantly the influence 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 to subsequently build a complex influenza virus immune history but very little is known about how the imprinting strain influences vaccine responses. To investigate the imprinted host immune responses 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 was given to build immune memory, ferrets were immunized and the challenge at Day 123. Samples were collected throughout the time course and immunological assays were performed to investigate recall mechanisms. The preimmune-vaccinated ferrets did not experience significant disease during challenge while naïve-vaccinated ferrets had severe disease. Hemagglutination inhibition assays showed preimmune ferrets had a more robust antibody response post vaccination, increased virus neutralization activity. Virus specific immunoglobulins were of predominantly the IgG isotype suggesting B cell maturity and plasticity at vaccination. These results are important and should be considered for vaccine design.

Keywords

influenza virus; imprinting; haemagglutinin; antibody titre; quadrivalent vaccine; influenza A; H1N1; split-virion; isotype; virus neutralization

Subject

Medicine and Pharmacology, Pathology and Pathobiology

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