Journal article
Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus
Journal of virology, Vol.61(2), pp.491-498
1987
DOI: 10.1128/jvi.61.2.491-498.1987
PMCID: PMC253973
PMID: 2433464
Abstract
Hepatitis A virus is an hepatotrophic human picornavirus which demonstrates little antigenic variability. To topologically map immunogenic sites on hepatitis A virus which elicit neutralizing antibodies, eight neutralizing monoclonal antibodies were evaluated in competition immunoassays employing radiolabeled monoclonal antibodies and HM-175 virus. Whereas two antibodies (K3-4C8 and K3-2F2) bound to intimately overlapping epitopes, the epitope bound by a third antibody (B5-B3) was distinctly different as evidenced by a lack of competition between antibodies for binding to the virus. The other five antibodies variably blocked the binding of both K3-4C8-K3-2F2 and B5-B3, suggesting that these epitopes are closely spaced and perhaps part of a single neutralization immunogenic site. Several combinations of monoclonal antibodies blocked the binding of polyclonal human covalescent antibody by greater than 96%, indicating that the neutralization epitopes bound by these antibodies are immunodominant in humans. Spontaneously arising HM-175 mutants were selected for resistance to monoclonal antibody-mediated neutralization. Fourteen clonally isolated mutants demonstrated substantial resistance to multiple monoclonal antibodies, including K3-4C8-K3-2F2 and B5-B3. In addition, 13 mutants demonstrated a 10-fold or greater reduction in neutralization mediated by polyclonal human antibody. Neutralization resistance was associated with reduced antibody binding. These results suggest that hepatitis A virus may differ from poliovirus in possessing a single, dominant neutralization immunogenic site and therefore may be a better candidate for synthetic peptide or antiidiotype vaccine development.
Details
- Title: Subtitle
- Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus
- Creators
- J. T Stapleton - University of North CarolinaS. M Lemon - Infectious Diseases
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.61(2), pp.491-498
- DOI
- 10.1128/jvi.61.2.491-498.1987
- PMID
- 2433464
- PMCID
- PMC253973
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 1987
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984297315902771
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