Abstract
Nonneutralizing Abs may play a role in protecting animals and humans from lentiviral infections. We explored the Ab-dependent, cell-mediated virus inhibition (ADCVI) Ab response to recombinant gp120 (rgp120) vaccination in sera from 530 participants in the Vax 004 trial. Serum ADCVI activity was measured against a clinical R5 strain of HIV-1 using peripheral blood mononuclear effector cells from healthy donors. The level of vaccine-induced ADCVI activity correlated inversely with the rate of acquiring HIV infection following vaccination, such that for every 10% increase in ADCVI activity, there was a 6.3% decrease in the hazard rate of infection (p=0.019). Some vaccinated individuals also mounted an ADCVI response against two other clinical R5 strains of HIV-1. However, ADCVI activity correlated poorly with neutralizing or CD4-gp120-blocking Ab activity measured against laboratory strains. Finally, the degree to which the ADCVI Ab response predicted the rate of infection was influenced by polymorphisms at the FcgammaRIIa and FcgammaRIIIa gene loci. These data indicate that rgp120 vaccination can elicit Abs with antiviral activity against clinical strains of HIV-1. However, such activity requires the presence of FcR-bearing effector cells. Our results provide further evidence that ADCVI may play a role in preventing HIV infection.
Publication types
-
Randomized Controlled Trial
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
AIDS Vaccines / administration & dosage
-
AIDS Vaccines / immunology*
-
Antibodies, Blocking / biosynthesis*
-
Antibodies, Blocking / metabolism
-
Antibodies, Blocking / physiology
-
Antibody-Dependent Cell Cytotoxicity* / genetics
-
Antigens, CD / genetics
-
HIV Antibodies / biosynthesis*
-
HIV Antibodies / metabolism
-
HIV Antibodies / physiology
-
HIV Envelope Protein gp120 / administration & dosage
-
HIV Envelope Protein gp120 / immunology*
-
HIV Infections / immunology*
-
HIV Infections / prevention & control
-
HIV Infections / virology
-
HIV-1 / growth & development*
-
HIV-1 / immunology
-
Humans
-
Immunity, Cellular / genetics
-
Killer Cells, Natural / immunology
-
Killer Cells, Natural / metabolism
-
Killer Cells, Natural / virology
-
Macrophages / immunology
-
Macrophages / metabolism
-
Macrophages / virology
-
Male
-
Neutralization Tests
-
Receptors, Fc / genetics
-
Receptors, Fc / metabolism*
-
Receptors, IgG / genetics
-
Vaccines, Subunit / administration & dosage
-
Vaccines, Subunit / immunology
-
Vaccines, Synthetic / administration & dosage
-
Vaccines, Synthetic / immunology
Substances
-
AIDS Vaccines
-
Antibodies, Blocking
-
Antigens, CD
-
FCGR3A protein, human
-
Fc gamma receptor IIA
-
HIV Antibodies
-
HIV Envelope Protein gp120
-
HIV-1 IIIB gp120 subunit vaccine
-
Receptors, Fc
-
Receptors, IgG
-
Vaccines, Subunit
-
Vaccines, Synthetic