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A Candidate H1N1 Pandemic Influenza Vaccine Elicits Protective Immunity in Mice

Steitz, Julia; Barlow, Peter G.; Hossain, Jaber; Kim, Eun; Okada, Kaori; Kenniston, Tom; Rea, Sheri; Donis, Ruben O.; Gambotto, Andrea

Authors

Julia Steitz

Jaber Hossain

Eun Kim

Kaori Okada

Tom Kenniston

Sheri Rea

Ruben O. Donis

Andrea Gambotto



Abstract

Background
In 2009 a new pandemic disease appeared and spread globally. The recent emergence of the pandemic influenza virus H1N1 first isolated in Mexico and USA raised concerns about vaccine availability. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model.

Methods
We generated two adenovirus(Ad5)-based influenza vaccine candidates encoding the wildtype or a codon-optimized hemagglutinin antigen (HA) from the recently emerged swine influenza isolate A/California/04/2009 (H1N1)pdm. After verification of antigen expression, immunogenicity of the vaccine candidates were tested in a mouse model using dose escalations for subcutaneous immunization. Sera of immunized animals were tested in microneutalization and hemagglutination inhibition assays for the presence of HA-specific antibodies. HA-specific T-cells were measured in IFNγ Elispot assays. The efficiency of the influenza vaccine candidates were evaluated in a challenge model by measuring viral titer in lung and nasal turbinate 3 days after inoculation of a homologous H1N1 virus.

Conclusions/Significance
A single immunization resulted in robust cellular and humoral immune response. Remarkably, the intensity of the immune response was substantially enhanced with codon-optimized antigen, indicating the benefit of manipulating the genetic code of HA antigens in the context of recombinant influenza vaccine design. These results highlight the value of advanced technologies in vaccine development and deployment in response to infections with pandemic potential. Our study emphasizes the potential of an adenoviral-based influenza vaccine platform with the benefits of speed of manufacture and efficacy of a single dose immunization

Journal Article Type Article
Acceptance Date Sep 1, 2010
Online Publication Date Sep 21, 2010
Publication Date Nov 30, 2010
Deposit Date Mar 27, 2012
Publicly Available Date Mar 27, 2012
Journal PLoS One
Print ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 5
Issue 5
Article Number e10492
DOI https://doi.org/10.1371/journal.pone.0010492
Keywords Influenza virus H1N1; vaccines; immunogenicity; immune response;
Public URL http://researchrepository.napier.ac.uk/id/eprint/5173
Publisher URL http://dx.doi.org/10.1371/journal.pone.0010492
Contract Date Mar 27, 2012

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Publisher Licence URL
http://creativecommons.org/licenses/by/3.0/

Copyright Statement
Copyright 2010 Steitz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited







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