MAPPING OF THE PRINCIPAL HUMAN IMMUNODEFICIENCY VIRUS NEUTRALIZING EPITOPE

Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.

MAPPING OF THE PRINCIPAL HUMAN IMMUNODEFICIENCY VIRUS NEUTRALIZING EPITOPE

Vaccines 88. New Chemical and Genetic Approaches to Vaccination: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Ginsberg H et al, eds. New York, Cold Spring Harbor Laboratory, p. 253-8, 1988.. Unique Identifier : AIDSLINE ICDB/89649765
Putney SD; Rusche JR; Javaherian K; Petro J; Lynn DL; O'Keeffe TJ; Grimaila R; McDanal C; Bolognesi DP; Matthews TJ; et al; Repligen Corp., Cambridge, MA 02139

Abstract: The synthesis of recombinant HIV proteins and peptides and their ability to elicit and block neutralizing antibodies are described. Immune sera elicited by recombinant proteins gp160 and PB1 were assayed for the ability to block the fusion of HIV-infected cells with uninfected CD4+ lymphocytes. Either anti-gp160 or anti-PB1 serum completely inhibited fusion. The inhibition of fusion by antisera to r160 or PB1 from the human T-lymphotropic virus IIIB isolate is HIV-variant-specific. Neutralization of cell-free virus by some antisera was also variant-specific in that they neutralized the homologous isolates but not heterologous isolates. Cell-fusion-inhibiting antibodies elicited by r160 or PB1 were competitively blocked by envelope proteins or fragments. A series of synthetic peptides were prepared from the amino-terminal cyanogen bromide fragment (CNBr1) region and assayed for their ability to block fusion inhibition. RP136 and RP135, which is a subset of 24 amino acids of RP136, blocked activity at concentrations equivalent to those of the larger fragments. It was demonstrated that the RP135 region of the envelope contains the dominant HIV-type-specific neutralizing epitope. The large majority of fusion-inhibiting antibodies are directed to this region. This does not rule out, however, the possibility that other envelope segments, perhaps those that are more conserved and play a role in CD4 binding, also elicit neutralizing antibodies. An effective HIV vaccine may need to contain both conserved and variable envelope regions. (6 Refs)

Keywords: Animal Chimpansee troglodytes Cloning, Molecular Epitopes/GENETICS/*IMMUNOLOGY Human HIV/GENETICS/*IMMUNOLOGY *Neutralization Tests Retroviridae Proteins/IMMUNOLOGY Vaccines, Synthetic/*IMMUNOLOGY Viral Envelope Proteins/IMMUNOLOGY Viral Fusion Proteins/IMMUNOLOGY Viral Vaccines/*IMMUNOLOGY MEETING PAPER

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