Article

Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus.

Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
PLoS ONE (Impact Factor: 3.53). 02/2009; 4(5):e5538. DOI: 10.1371/journal.pone.0005538
Source: PubMed

ABSTRACT Annual vaccination against seasonal influenza viruses is recommended for certain individuals that have a high risk for complications resulting from infection with these viruses. Recently it was recommended in a number of countries including the USA to vaccinate all healthy children between 6 and 59 months of age as well. However, vaccination of immunologically naïve subjects against seasonal influenza may prevent the induction of heterosubtypic immunity against potentially pandemic strains of an alternative subtype, otherwise induced by infection with the seasonal strains. Here we show in a mouse model that the induction of protective heterosubtypic immunity by infection with a human A/H3N2 influenza virus is prevented by effective vaccination against the A/H3N2 strain. Consequently, vaccinated mice were no longer protected against a lethal infection with an avian A/H5N1 influenza virus. As a result H3N2-vaccinated mice continued to loose body weight after A/H5N1 infection, had 100-fold higher lung virus titers on day 7 post infection and more severe histopathological changes than mice that were not protected by vaccination against A/H3N2 influenza. The lack of protection correlated with reduced virus-specific CD8+ T cell responses after A/H5N1 virus challenge infection. These findings may have implications for the general recommendation to vaccinate all healthy children against seasonal influenza in the light of the current pandemic threat caused by highly pathogenic avian A/H5N1 influenza viruses.

0 Bookmarks
 · 
103 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Vaccination is by far the most effective way of preventing morbidity and mortality due to infection of the upper respiratory tract by influenza virus. Current vaccines require yearly vaccine updates as the influenza virus can escape vaccine-induced humoral immunity due to the antigenic variability of its surface antigens. In case of a pandemic, new vaccines become available too late with current vaccine practices. New technologies that allow faster production of vaccine seed strains in combination with alternative production platforms and vaccine formulations may shorten the time gap between emergence of a new influenza virus and a vaccine becoming available. Adjuvants may allow antigen-sparing, allowing more people to be vaccinated with current vaccine production capacity. Adjuvants and universal vaccines can target immune responses to more conserved influenza epitopes, which eventually will result in broader protection for a longer time. In addition, further immunological studies are needed to gain insights in the immune features that contribute to protection from influenza-related disease and mortality, allowing redefinition of correlates of protection beyond virus neutralization in vitro.
    Viruses. 01/2014; 6(10):3809-3826.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Vaccines used against seasonal influenza are poorly effective against influenza A viruses of novel subtypes that may have pandemic potential. Furthermore, pre(pandemic) influenza vaccines are poorly immunogenic, which can be overcome by the use of adjuvants. A limited number of adjuvants has been approved for use in humans, however there is a need for alternative safe and effective adjuvants that can enhance the immunogenicity of influenza vaccines and that promote the induction of broad-protective T cell responses. Here we evaluated a novel nanoparticle, G3, as an adjuvant for a seasonal trivalent inactivated influenza vaccine in a mouse model. The G3 adjuvant was formulated with or without steviol glycosides (DT, for diterpenoid). The use of both formulations enhanced the virus-specific antibody response to all three vaccine strains considerably. The adjuvants were well tolerated without any signs of discomfort. To assess the protective potential of the vaccine-induced immune responses, an antigenically distinct influenza virus strain, A/Puerto Rico/8/34 (A/PR/8/34), was used for challenge infection. The vaccine-induced antibodies did not cross-react with strain A/PR/8/34 in HI and VN assays. However, mice immunized with the G3/DT-adjuvanted vaccine were partially protected against A/PR/8/34 infection, which correlated with the induction of anamnestic virus-specific CD8+ T cell responses that were not observed with the use of G3 without DT. Both formulations induced maturation of human dendritic cells and promoted antigen presentation to a similar extent. In conclusion, G3/DT is a promising adjuvant formulation that not only potentiates the antibody response induced by influenza vaccines, but also induces T cell immunity which could afford broader protection against antigenically distinct influenza viruses.
    Vaccine 09/2014; 32(43):5614–5623. · 3.49 Impact Factor
  • Future Virology 11/2012; 7(11):1065-1076. · 1.00 Impact Factor

Full-text (2 Sources)

Download
28 Downloads
Available from
May 22, 2014