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A candidate H1N1 pandemic influenza vaccine elicits protective immunity in mice.

Steitz J, Barlow PG, Hossain J, Kim E, Okada K, Kenniston T, Rea S, Donis RO, Gambotto A - PLoS ONE (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

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 IFNgamma 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.

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Induced protection against H1N1 by the H1N1 vaccine candidates.Protection of immunized animals (5 or 6 weeks after immunization with AdHA.wt vs Ad5 control or AdHA.cod vs Ad5 control) against an intranasal challenge with 1000 pfu of A/Ohio/7/09 (H1N1)pdm was measured as viral titers in lung and nasal turbinate determined 3 days post-inoculation in a plaque formation assay using MDCK-L cells. Shown are log10 values of mean titer for each group ± SEM. The horizontal dashed line represents the lower limit of detection of the assay.
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pone-0010492-g003: Induced protection against H1N1 by the H1N1 vaccine candidates.Protection of immunized animals (5 or 6 weeks after immunization with AdHA.wt vs Ad5 control or AdHA.cod vs Ad5 control) against an intranasal challenge with 1000 pfu of A/Ohio/7/09 (H1N1)pdm was measured as viral titers in lung and nasal turbinate determined 3 days post-inoculation in a plaque formation assay using MDCK-L cells. Shown are log10 values of mean titer for each group ± SEM. The horizontal dashed line represents the lower limit of detection of the assay.

Mentions: To investigate the protective efficacy of these AdHA vaccine candidates against challenge with the H1N1 virus we utilized a mouse model [17]. Animals were intranasally inoculated with 1000 PFU A/Ohio/7/09 (H1N1)pdm 5 to 6 weeks after the single dose immunization. Three days post-challenge, the mice were sacrificed, their lungs and nasal turbinate harvested and viral titers were determined by plaque formation assay performed in MDCK-L cells. As expected, the mock-immunized group had positive H1N1 titer in lung and nasal turbinate. No measurable virus titers were detected in lung and nasal turbinate in the AdHA.cod immunized group (Fig. 3). Somewhat lower levels of protection were observed in the AdHA.wt immunized group. As shown in table 1, in AdHA.wt immunized group 2 out of 10 animals had positive H1N1 titer revealing a correlation between the magnitude of the immune response and protection from H1N1 challenge.


A candidate H1N1 pandemic influenza vaccine elicits protective immunity in mice.

Steitz J, Barlow PG, Hossain J, Kim E, Okada K, Kenniston T, Rea S, Donis RO, Gambotto A - PLoS ONE (2010)

Induced protection against H1N1 by the H1N1 vaccine candidates.Protection of immunized animals (5 or 6 weeks after immunization with AdHA.wt vs Ad5 control or AdHA.cod vs Ad5 control) against an intranasal challenge with 1000 pfu of A/Ohio/7/09 (H1N1)pdm was measured as viral titers in lung and nasal turbinate determined 3 days post-inoculation in a plaque formation assay using MDCK-L cells. Shown are log10 values of mean titer for each group ± SEM. The horizontal dashed line represents the lower limit of detection of the assay.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864737&req=5

pone-0010492-g003: Induced protection against H1N1 by the H1N1 vaccine candidates.Protection of immunized animals (5 or 6 weeks after immunization with AdHA.wt vs Ad5 control or AdHA.cod vs Ad5 control) against an intranasal challenge with 1000 pfu of A/Ohio/7/09 (H1N1)pdm was measured as viral titers in lung and nasal turbinate determined 3 days post-inoculation in a plaque formation assay using MDCK-L cells. Shown are log10 values of mean titer for each group ± SEM. The horizontal dashed line represents the lower limit of detection of the assay.
Mentions: To investigate the protective efficacy of these AdHA vaccine candidates against challenge with the H1N1 virus we utilized a mouse model [17]. Animals were intranasally inoculated with 1000 PFU A/Ohio/7/09 (H1N1)pdm 5 to 6 weeks after the single dose immunization. Three days post-challenge, the mice were sacrificed, their lungs and nasal turbinate harvested and viral titers were determined by plaque formation assay performed in MDCK-L cells. As expected, the mock-immunized group had positive H1N1 titer in lung and nasal turbinate. No measurable virus titers were detected in lung and nasal turbinate in the AdHA.cod immunized group (Fig. 3). Somewhat lower levels of protection were observed in the AdHA.wt immunized group. As shown in table 1, in AdHA.wt immunized group 2 out of 10 animals had positive H1N1 titer revealing a correlation between the magnitude of the immune response and protection from H1N1 challenge.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

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 IFNgamma 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.

Show MeSH
Related in: MedlinePlus