Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus

Journal Article · Sun Feb 01 00:00:00 EST 1987 · J. Virol.; (United States)

OSTI ID:6204392

Stapleton, J T; Lemon, S M

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 convalescent 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. 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.

• Research Organization: Univ. of North Carolina, Chapel Hill (USA)
• OSTI ID: 6204392
• Journal Information: J. Virol.; (United States), Vol. 61:2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
INFECTIOUS HEPATITIS
IMMUNOLOGY
MONOCLONAL ANTIBODIES
RADIOIMMUNOASSAY
VIRUSES
MUTANTS
ANIMAL CELLS
ANTIGENS
HYBRIDIZATION
IODINE 125
KIDNEYS
MONKEYS
PHOSPHORUS 32
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
IMMUNOASSAY
INFECTIOUS DISEASES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MICROORGANISMS
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANS
PARASITES
PHOSPHORUS ISOTOPES
PRIMATES
RADIOASSAY
RADIOIMMUNOLOGY
RADIOISOTOPES
TRACER TECHNIQUES
VERTEBRATES
VIRAL DISEASES
550701* - Microbiology- Tracer Techniques