Article

Comparative Efficacy of Neutralizing Antibodies Elicited by Recombinant Hemagglutinin Proteins from Avian H5N1 Influenza Virus

Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, USA.
Journal of Virology (Impact Factor: 4.44). 08/2008; 82(13):6200-8. DOI: 10.1128/JVI.00187-08
Source: PubMed

ABSTRACT

Although the human transmission of avian H5N1 virus remains low, the prevalence of this highly pathogenic infection in avian species underscores the need for a preventive vaccine that can be made without eggs. Here, we systematically analyze various forms of recombinant hemagglutinin (HA) protein for their potential efficacy as vaccines. Monomeric, trimeric, and oligomeric H5N1 HA proteins were expressed and purified from either insect or mammalian cells. The immunogenicity of different recombinant HA proteins was evaluated by measuring the neutralizing antibody response. Neutralizing antibodies to H5N1 HA were readily generated in mice immunized with the recombinant HA proteins, but they varied in potency depending on their multimeric nature and cell source. Among the HA proteins, a high-molecular-weight oligomer elicited the strongest antibody response, followed by the trimer; the monomer showed minimal efficacy. The coexpression of another viral surface protein, neuraminidase, did not affect the immunogenicity of the HA oligomer, as expected from the immunogenicity of trimers produced from insect cells. As anticipated, HA expressed in mammalian cells without NA retained the terminal sialic acid residues and failed to bind alpha2,3-linked sialic acid receptors. Taken together, these results suggest that recombinant HA proteins as individual or oligomeric trimers can elicit potent neutralizing antibody responses to avian H5N1 influenza viruses.

Download full-text

Full-text

Available from: James Stevens
  • Source
    • "This makes it a fallow ground for influenza vaccines development, considering the advantages accorded it by many authors. E. coli vectors are extensively utilized in the development of influenza vaccines and several of these vaccines have been shown to be effective in animal models (Song et al., 2008; Wei et al., 2008; Aguilar- Yanez et al., 2010; DuBois et al., 2011). For instance many study groups have produced influenza recombinant HA in E. coli which are immunogenic in animals (Treanor et al., 2010; Liu et al., 2009; Taylor et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Africa is experiencing reoccurrence of avian influenza outbreaks with huge negative impact on the economy of the continent as a result of high mortality rate and extreme contagiousness of the disease. The epidemiology of highly pathogenic avian influenza (HPAI) in Africa during the 2006-2008 outbreaks was complex and linked to movements of poultry commodities and wild birds. The peculiar risk factors, negative economic impact and the potential of being used as a biological weapon necessitates the development of a comprehensive control programme for the prevention or eradication of the disease. It is the opinion of this paper that development of new influenza vaccine technologies will provide affordable comprehensive control programmes for avian influenza prevention in Africa. To keep pace with the variability of the viruses, there is need for frequent redesign of avian influenza (AI) vaccines to match the circulating subtypes and on this is predicated the necessity of the development of influenza vaccine technology for a country, zone or region. The new vaccine technologies have been shown to have the potentials of giving vaccines with required criteria of purity, safety, efficacy, potency, low cost and short response time. The concept of most new vaccine technologies is biased towards removal of influenza virus from the system of vaccine development and at the same time obtaining more effective, potent and safe influenza vaccines. The new influenza vaccine technologies include gene-based, genomics-based, subunit, plant-based, VLPs and universal vaccine technologies. These technologies have the potential to provide vaccines that will not just be used as intervention strategies to lessen severity of the disease but as preventative vaccination. Also routine vaccination will not just be as a tool of last option in disease endemic areas, but one to prevent the disease.
    Full-text · Article · Aug 2015
  • Source
    • "This makes it a fallow ground for influenza vaccines development, considering the advantages accorded it by many authors. E. coli vectors are extensively utilized in the development of influenza vaccines and several of these vaccines have been shown to be effective in animal models (Song et al., 2008; Wei et al., 2008; Aguilar- Yanez et al., 2010; DuBois et al., 2011). For instance many study groups have produced influenza recombinant HA in E. coli which are immunogenic in animals (Treanor et al., 2010; Liu et al., 2009; Taylor et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Africa is experiencing reoccurrence of avian influenza outbreaks with huge negative impact on the economy of the continent as a result of high mortality rate and extreme contagiousness of the disease. The epidemiology of highly pathogenic avian influenza (HPAI) in Africa during the 2006-2008 outbreaks was complex and linked to movements of poultry commodities and wild birds. The peculiar risk factors, negative economic impact and the potential of being used as a biological weapon necessitates the development of a comprehensive control programme for the prevention or eradication of the disease. It is the opinion of this paper that development of new influenza vaccine technologies will provide affordable comprehensive control programmes for avian influenza prevention in Africa. To keep pace with the variability of the viruses, there is need for frequent redesign of avian influenza (AI) vaccines to match the circulating subtypes and on this is predicated the necessity of the development of influenza vaccine technology for a country, zone or region. The new vaccine technologies have been shown to have the potentials of giving vaccines with required criteria of purity, safety, efficacy, potency, low cost and short response time. The concept of most new vaccine technologies is biased towards removal of influenza virus from the system of vaccine development and at the same time obtaining more effective, potent and safe influenza vaccines. The new influenza vaccine technologies include gene-based, genomics-based, subunit, plant-based, VLPs and universal vaccine technologies. These technologies have the potential to provide vaccines that will not just be used as intervention strategies to lessen severity of the disease but as preventative vaccination. Also routine vaccination will not just be as a tool of last option in disease endemic areas, but one to prevent the disease.
    Full-text · Article · Aug 2015
  • Source
    • "This makes it a fallow ground for influenza vaccines development, considering the advantages accorded it by many authors. E. coli vectors are extensively utilized in the development of influenza vaccines and several of these vaccines have been shown to be effective in animal models (Song et al., 2008; Wei et al., 2008; Aguilar- Yanez et al., 2010; DuBois et al., 2011). For instance many study groups have produced influenza recombinant HA in E. coli which are immunogenic in animals (Treanor et al., 2010; Liu et al., 2009; Taylor et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Reverse transcription polymerase chain reaction (RT-PCR) and partial sequencing of the VP2 hypervariable region was performed on clinical samples from two infectious bursal disease (IBD) outbreaks in Plateau state, Nigeria. IBD virus RNA was detected in all four bursa of Fabricius samples. Nucleotide sequencing and analysis of the four samples revealed high similarity to previous IBDV sequences from northern and southern Nigeria. The deduced amino acid sequences were compared to reference IBDV strains retrieved from the GenBank; virulence markers A222, I256, and I294 were conserved in both outbreak and reference sequences. Amino acid residue S254 was conserved in the outbreak viruses and previous viruses from northern Nigeria. Phylogenetic analysis revealed that all four viruses were very virulent IBDVs. These viruses clustered with vv2-1 variant viruses from Oyo and Ogun states and less closely with vv2-2 isolates from Tanzania. The nucleotide identity of the sequences in this study ranged from 99.6 to 100 % with each other. These findings are further evidence of IBD outbreaks in vaccinated chicken flocks in Nigeria.
    Full-text · Article · Jul 2015 · Tropical Animal Health and Production
Show more