Abstract
BackgroundIn 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.MethodsWe 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/SignificanceA 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.
Highlights
Events of the past six months have brought home to the world that a new pandemic disease has appeared in our midst
Four weeks after immunization serum samples were obtained from all mice to screen for H1N1 specific antibodies in hemagglutination inhibition (HI) assay using the influenza strain A/Texas/05/09 (H1N1)pdm as source of homologous antigen
This study demonstrates that a single-dose of codon-optimized adenovirus-based H1N1 vaccine expressing hemagglutinin antigen (HA) derived from influenza virus A/California/04/2009 (H1N1)pdm efficiently induces HA-specific antibodies and T-cells in mice that correlates with protection when measured as the elimination of detectable virus titers in lungs and nasal turbinates 3 days after challenge
Summary
Events of the past six months have brought home to the world that a new pandemic disease has appeared in our midst. The pandemic caused by a swine-origin influenza virus A H1N1 and first isolated from humans in Mexico and the USA has spread globally [1,2,3]. A monovalent influenza virus vaccine has been rapidly produced by standard techniques and is being evaluated in clinical trials [9] It appears that the production of large amounts of egg-produced swine influenza H1N1 vaccine has limited capability due to suboptimal yields This could severely hinder the ability to produce large amount of vaccines in a timely manner for efficient control of pandemic spread via vaccination. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model
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