Vaccination against Human Influenza A/H3N2 Virus Prevents the Induction of Heterosubtypic Immunity against Lethal Infection with Avian Influenza A/H5N1 Virus

University of Pretoria, South Africa
PLoS ONE (Impact Factor: 3.23). 02/2009; 4(5):e5538. DOI: 10.1371/journal.pone.0005538
Source: PubMed


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.

Download full-text


Available from: Judith M A van den Brand, Oct 04, 2015
11 Reads
  • Source
    • "Furthermore, slides were stained using an immunoperoxidase method with an antibody (rabbit anti-M2, 1∶500) directed against the matrix protein-2 of influenza A virus. A Goat-anti-rabbit IgG HRP (1∶2000, Sigma-Aldrich, St. Louis, USA) was used as the secondary antibody for the detection of virus infected cells in respective tissues [57]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To develop a safe and effective mucosal vaccine against pathogenic influenza viruses, we constructed recombinant Lactobacillus casei strains that express conserved matrix protein 2 with (pgsA-CTA1-sM2/L. casei) or without (pgsA-sM2/L. casei) cholera toxin subunit A1 (CTA1) on the surface. The surface localization of the fusion protein was verified by cellular fractionation analyses, flow cytometry and immunofluorescence microscopy. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA. However, the conjugation of cholera toxin subunit A1 induced more potent mucosal, humoral and cell-mediated immune responses. In a challenge test with 10 MLD50 of A/EM/Korea/W149/06(H5N1), A/Puerto Rico/8/34(H1N1), A/Aquatic bird /Korea/W81/2005(H5N2), A/Aquatic bird/Korea/W44/2005(H7N3), and A/Chicken/Korea/116/2004(H9N2) viruses, the recombinant pgsA-CTA1-sM2/L. casei provided better protection against lethal challenges than pgsA-sM2/L. casei, pgsA/L. casei and PBS in mice. These results indicate that mucosal immunization with recombinant L. casei expressing CTA1-conjugated sM2 protein on its surface is an effective means of eliciting protective immune responses against diverse influenza subtypes.
    PLoS ONE 04/2014; 9(4):e94051. DOI:10.1371/journal.pone.0094051 · 3.23 Impact Factor
  • Source
    • "In addition, 2 previous studies investigated vaccination with homologous challenge (non-lethal virus) followed by heterologous challenge (lethal virus) [53,54] and showed that vaccines were efficient in protecting against homologous challenge but failed in protecting against heterologous challenge. In these same studies, non-vaccinated animals became sick when challenged with non-lethal virus but survived when challenged with lethal virus. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Whole inactivated vaccines (WIVs) possess greater immunogenicity than split or subunit vaccines, and recent studies have demonstrated that WIVs with preserved fusogenic activity are more protective than non-fusogenic WIVs. In this work, we describe the inactivation of human influenza virus X-31 by high hydrostatic pressure (HHP) and analyze the effects on the structure by spectroscopic measurements, light scattering, and electron microscopy. We also investigated the effects of HHP on the glycoprotein activity and fusogenic activity of the viral particles. The electron microscopy data showed pore formation on the viral envelope, but the general morphology was preserved, and small variations were seen in the particle structure. The activity of hemagglutinin (HA) during the process of binding and fusion was affected in a time-dependent manner, but neuraminidase (NA) activity was not affected. Infectious activity ceased after 3 hours of pressurization, and mice were protected from infection after being vaccinated. Our results revealed full viral inactivation with overall preservation of viral structure and maintenance of fusogenic activity, thereby conferring protection against infection. A strong response consisting of serum immunoglobulin IgG1, IgG2a, and serum and mucosal IgA was also detected after vaccination. Thus, our data strongly suggest that applying hydrostatic pressure may be an effective method for developing new vaccines against influenza A as well as other viruses.
    PLoS ONE 11/2013; 8(11):e80785. DOI:10.1371/journal.pone.0080785 · 3.23 Impact Factor
  • Source
    • "). Due to its antigenic similarity, influenza A H3N2 virus can be used as surrogate for pandemic (Mahony et al. 2010) and highly pathogenic AIV (Bodewes et al. 2009) (for example, vaccination and antiviral resistance test). The aim of this study was to investigate the potential virucidal efficacy of the novel sanitizer (levulinic acid plus SDS) against Influenza A H3N2 virus on egg surfaces. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Influenza A virus poses a major public health concern and is associated with annual epidemics and occasional pandemics. Influenza A H3N2 viruses, which are an important cause of human influenza, can infect birds and mammals. Contaminated undercooked poultry products including eggs with avian influenza virus constitute a possible risk of transmission to humans. In this study, a novel levulinic acid plus sodium dodecyl sulfate (SDS) sanitizer was evaluated for eggshell decontamination. Influenza A H3N2 virus-inoculated chicken eggshells were treated with a 5 % levulinic acid plus 2 % SDS, 2 % levulinic acid plus 1 % SDS, and 0.5 % levulinic acid plus 0.5 % SDS liquid solution for 1 min. Log reductions of viable viruses were observed by plaque assay. The 5 % levulinic acid plus 2 % SDS sanitizer provided the greatest level of influenza A H3N2 virus inactivation (2.23 log PFU), and differences in virus inactivation were observed for the various levulinic acid plus SDS concentrations tested (P ≤ 0.05). To the best of our knowledge, this is the first study demonstrating influenza A H3N2 virus inactivation on eggshells using a novel levulinic acid plus SDS sanitizer. The sanitizer may be useful for reducing egg contamination and preventing the spread of avian influenza virus to humans.
    Food and Environmental Virology 10/2013; 5(4). DOI:10.1007/s12560-013-9129-x · 2.36 Impact Factor
Show more