Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140.
The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss, J. Virol. 68:3015-3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHIV-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication.
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- env Gene Products, Human Immunodeficiency Virus
- Virus Replication
- Virology
- Vaccination
- Simian immunodeficiency virus
- Simian Immunodeficiency Virus
- Simian Acquired Immunodeficiency Syndrome
- Rabbits
- Peptide Fragments
- Neutralization Tests
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- env Gene Products, Human Immunodeficiency Virus
- Virus Replication
- Virology
- Vaccination
- Simian immunodeficiency virus
- Simian Immunodeficiency Virus
- Simian Acquired Immunodeficiency Syndrome
- Rabbits
- Peptide Fragments
- Neutralization Tests