Hemagglutinin stalk domain from H5N1 strain as a potentially universal antigen.

Abstract

Influenza A virus infections are the major public health concern and cause significant morbidity and mortality each year worldwide. Vaccination is the main strategy of influenza epidemic prevention. However, seasonal vaccines induce strain-specific immunity and must be reformulated annually based on prediction of the strains that will circulate in the next season. Thus, it is essential to develop vaccines that would induce broad and persistent immunity to influenza viruses. Hemagglutinin is the major surface antigen of the influenza virus. Recent studies revealed the importance of HA stalk-specific antibodies in neutralization of different influenza virus strains. Therefore, it is important to design an immunogen that would focus the immune response on the HA stalk domain in order to elicit neutralizing antibodies. In the present study, we report characterization of a conserved truncated protein, potentially a universal influenza virus antigen from the H5N1 Highly Pathogenic Avian Influenza A virus strain. Our results indicate that exposure of the HA stalk domain containing conserved epitopes results in cross reactivity with different antibodies (against group 1 and 2 HAs). Additionally, we conclude that HA stalk domain contains not only conformational epitopes recognized by universal FI6 antibody, but also linear epitopes recognized by other antibodies. Abbreviations: HA, hemagglutinin; PAb, polyclonal antibody; MAb, monoclonal antibody; HPAI, highly pathogenic avian influenza; pH1N1, pandemic strain H1N1; rHA, recombinant hemagglutinin; WT AcNPV, Autographa californica nuclear polyhedrosis virus wild type strain.

Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1

“…Recent trends in influenza vaccine development have followed two general paths: a universal vaccine approach using the stalk domain to induce a broad-spectrum neutralizing antibody, and a specific approach using VLPs [ 33 , 34 ]. In addition to their advantages of improved safety and strong immune response, VLP vaccines can readily substitute HA or NA genes to allow rapid, dynamic responses to a new influenza outbreak [ 14 , 35 , 36 ].…”

Broadly protective immunity against divergent influenza viruses by oral co-administration of Lactococcus lactis expressing nucleoprotein adjuvanted with cholera toxin B subunit in mice

“…It is well known that the development of a universal influenza vaccine relies on highly conserved regions of antigens [ 6 , 7 ], such as the stalk domain of the HA [ 8 , 9 ], the amino terminus of the M2 proteins (M2e or M2 ectodomain) [ 10 ] and the nucleoprotein (NP) [ 11 ]. Of note, phylogenetic analysis of virus strains isolated from different hosts indicates that the NP is relatively well conserved [ 12 ].…”

Recent outbreaks of highly pathogenic avian influenza viruses in South Korea

“…The globular head domain of HA plays a critical role in producing potent neutralizing antibodies, which indicates that HA can induce the production of neutralizing antibodies against only homologous viruses [ 1 77 ]. Therefore, many investigators demonstrated that highly conserved sequences such as the stem region of HA (called HA2 ) and M2e are more desirable targets for generating a universal vaccine [ 78 79 80 ]. Consist with the above results, our group also confirmed that the HA2 domain induced the production of a broad spectrum of neutralizing activities against different avian strains containing H5 subtypes (unpublished).…”