Cross-Glade protective immunity of H5N1 influenza vaccines in a mouse model

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Vaccine (Impact Factor: 3.62). 10/2008; 26(50):6398-404. DOI: 10.1016/j.vaccine.2008.08.053
Source: PubMed


H5N1 highly pathogenic avian influenza viruses evolved into several clades, leading to appreciably distinct antigenicities of their hemagglutinins. As such, candidate H5N1 pre-pandemic vaccines for human use should be sought. Here, to evaluate fundamental immunogenic variations between H5N1 vaccines, we prepared four inactivated H5N1 test vaccines from different phylogenetic clades (clade 1, 2.1, 2.2, and 2.3.4) in accordance with the WHO recommendation, and tested their cross-clade immunity in a mouse model by vaccination followed by challenge with heterologous virulent viruses. All H5N1 vaccines tested provided full or partial cross-clade protective immunity, except one clade 2.2-based vaccine, which did not protect mice from clade 2.3.4 virus challenge. Among the test vaccines, a clade 2.1-based vaccine possessed the broadest-spectrum cross-immunity. These results suggest that currently stockpiled pre-pandemic vaccines, especially clade 2.1-based vaccines, will likely be useful as backup vaccines in a pandemic situation, even one involving antigenic-drifted viruses.

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Available from: Chairul A Nidom, Mar 11, 2014
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    • "However, H5N1 HPAIVs have genetically been divided into several clades according to HA sequences, and further evolution of the virus has led to the appearance of new clades and subclades as of 2012 [7], [8]. Therefore, it is thought that vaccine strains should be renewed according to circulating strains, and the development of a vaccine that is effective against a broad spectrum of different clades is required [9]. "
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    ABSTRACT: H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.
    Full-text · Article · Dec 2013 · PLoS ONE
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    • "Because the eventual pandemic virus may be an antigenic drift variant of the strain used to produce such pre-pandemic vaccines, a complete match with the pandemic strain cannot be guaranteed. However, the above vaccines have been shown to induce substantial cross-reactive immune responses to viruses of different H5N1 clades (16–18,20–23). Moreover, even at suboptimal efficacy, pre-pandemic vaccines may reduce attack rates if deployed in an early stage of the pandemic (24,25) or may serve as priming dose for the true pandemic vaccine, thus saving time and resources (26). "
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    ABSTRACT: Stockpiling of pre-pandemic influenza vaccines guarantees immediate vaccine availability to counteract an emerging pandemic. Generally, influenza vaccines need to be stored and handled refrigerated to prevent thermal degradation of the antigenic component. Requirement of a cold-chain, however, complicates stockpiling and the logistics of vaccine distribution. We, therefore, investigated the effect of elevated storage temperatures on the immunogenicity of a pre-pandemic influenza A H5N1 whole inactivated virus vaccine. Either suspended in liquid or kept as a freeze-dried powder, vaccines could be stored for 1 year at ambient temperature (20 degrees C) with minimal loss of immunogenicity in mice. Elevation of the storage temperature to 40 degrees C, however, resulted in a significant loss of immunogenic potency within 3 months if vaccines were stored in liquid suspension. In sharp contrast, freeze-dried powder formulations were stable at 40 degrees C for at least 3 months. The presence of inulin or trehalose sugar excipients during freeze-drying of the vaccine proved to be critical to maintain its immunogenic potency during storage, and to preserve the characteristic Th1-type response to whole inactivated virus vaccine. These results indicate that whole inactivated virus vaccines may be stored and handled at room temperature in moderate climate zones for over a year with minimal decline and, if converted to dry-powder, even in hot climate zones for at least 3 months. The increased stability of dry-powder vaccine at 40 degrees C may also point to an extended shelf-life when stored at 4 degrees C. Use of the more stable dry-powder formulation could simplify stockpiling and thereby facilitating successful pandemic intervention.
    Full-text · Article · Mar 2010 · The AAPS Journal
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    • "Accumulating evidence has shown that HPAI H5N1 virus has evolved into several clades, which has led to distinct antigenicities of their hemagglutinins (Murakami et al., 2008). Thus, an ideal vaccine against H5N1 avian influenza should overcome the antigenic variability of the virus. "
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    ABSTRACT: Baculovirus has emerged recently as a novel and attractive gene delivery vehicle for mammalian cells. In this study, baculovirus pseudotyped with vesicular stomatitis virus glycoprotein was used as a vector to express the hemagglutinin (HA) protein of highly pathogenic H5N1 avian influenza virus, A/Chicken/Hubei/327/2004 (HB/327). The resultant recombinant baculovirus (BV-G-HA) mediated gene delivery and HA expression efficiently in mammalian cells. Mice immunized with 1 x 10(9)PFU of BV-G-HA developed significantly higher levels of H5-specific antibodies and cellular immunity than those that received 100 microg of DNA vaccines expressing HA, and were completely protected from lethal challenge with HB/327. Different vaccination doses were further tested in chickens, and these experiments demonstrated that 1 x 10(8)PFU of BV-G-HA offered complete protection from challenge with 100 LD(50) of HB/327. These data indicate that the pseudotype baculovirus-mediated vaccine could be utilized as an alternative strategy against the pandemic spread of H5N1 influenza virus.
    Full-text · Article · Jun 2009 · Molecular Immunology
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