UMMS Affiliation

Department of Medicine; Department of Biochemistry and Molecular Pharmacology

Publication Date

9-22-2006

Document Type

Article

Subjects

Animals; Antibodies, Viral; Antibody Specificity; Codon; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Influenza A Virus, H3N2 Subtype; Influenza A virus; Influenza Vaccines; Mice; Mice, Inbred BALB C; Rabbits; Vaccines, DNA

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Effective antibody responses provide crucial immunity against influenza virus infection. The hemagglutinin (HA) protein is the major target of protective antibody responses induced by viral infection and by vaccination with both inactivated and live-attenuated flu vaccines, but knowledge about the optimal designs of protective HA antigens from different flu serotypes is still limited. In this study, we have significantly improved the immunogenicity of HA-expressing DNA vaccines by using codon-optimized HA sequences for either an H1 serotype (A/NewCal/20/99) or an H3 serotype (A/Panama/2007/99) human influenza A virus and then used these constructs as model antigens to identify the optimal HA antigen designs to elicit high-level protective antibody responses. Two forms of HA antigen, a wild-type, full-length HA and a secreted form with transmembrane (TM) domain-truncated HA, were produced. Both forms of HA DNA vaccines, from either H1 or H3 serotypes, were able to elicit high levels of HA-specific immunoglobulin G responses in immunized rabbits as measured by enzyme-linked immunosorbent assay. Interestingly, the abilities of H1 HA and H3 HA antigens to elicit hemagglutination inhibition (HI) and neutralizing antibody (NAb) responses differ. For the H1 HA antigens, the full-length HA induced significantly higher HI and NAb responses than did the TM-truncated HA. For the H3 HA antigen, both the full-length HA and TM-truncated HA induced high levels of HI and NAb responses. These data indicate that H1 and H3 antigens have different expression requirements for the induction of an optimal protective antibody response and that the structure integrity of HA antigens is critical for eliciting type-specific protective antibody responses. Our findings will have an important impact on future subunit-based flu vaccine development.

Rights and Permissions

Citation: J Virol. 2006 Dec;80(23):11628-37. Epub 2006 Sep 20. Link to article on publisher's site

DOI of Published Version

10.1128/JVI.01065-06

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of virology

PubMed ID

16987975

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