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A candidate H1N1 pandemic influenza vaccine elicits protective immunity in Mice

Steitz, J and Barlow, PG and Hossain, J and Kim, E and Okada, K and Kenniston, T and Rea, S and Donis, RO and Gambotto, A (2010) A candidate H1N1 pandemic influenza vaccine elicits protective immunity in Mice. PLoS ONE, 5 (5).

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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 codonoptimized 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. © 2010 Steitz et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Steitz, J
Barlow, PG
Hossain, J
Kim, Eeuk10@pitt.eduEUK10
Okada, K
Kenniston, T
Rea, S
Donis, RO
Gambotto, Aagamb@pitt.eduAGAMB
ContributionContributors NameEmailPitt UsernameORCID
Date: 17 September 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0010492
Schools and Programs: School of Medicine > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: Animals; Cell Line, Tumor; Disease Outbreaks; Female; Humans; Immunity--immunology; Immunity, Cellular; Immunity, Humoral; Influenza A Virus, H1N1 Subtype--immunology; Influenza Vaccines--immunology; Influenza, Human--epidemiology; Influenza, Human--immunology; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections--epidemiology; Orthomyxoviridae Infections--immunology; Orthomyxoviridae Infections--prevention & control; Reproducibility of Results
Other ID: NLM PMC2864737
PubMed Central ID: PMC2864737
PubMed ID: 20463955
Date Deposited: 03 Aug 2012 20:54
Last Modified: 01 Mar 2019 14:56


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