Broadly reactive antibody-dependent cellular cytotoxic response to HIV-1 envelope glycoproteins precedes broad neutralizing response in human infection.
To determine if and when the antibody-dependent cell-mediated cytotoxic (ADCC) response of human serum exhibits broad reactivity across HIV-1 strains, multiple sera were tested for their ability to mediate ADCC against target cells infected with recombinant vaccinia vectors expressing envelope genes of HTLV-IIIB or HTLV-IIIRF. These vectors were found to express the envelope glycoproteins of the two HIV-1 strains and so were appropriate targets for ADCC assays. All the HIV-1-positive sera were able to mediate ADCC against both HTLV-IIIB and HTLV-IIIRF envelope-expressing targets at similar titer. In sera from early seroconverters, the ADCC response was again broadly reactive, even in those sera that exhibited strain-specific neutralizing antibody responses. The ADCC response to natural infection with HIV-1 is therefore broadly reactive and precedes the development of a broad neutralizing antibody response. The broad reactivity of HIV-1-specific ADCC responses may be important for protection against cell-associated virus in vaccine development.
Koup
R A
RA
Department of Pediatrics, University of Massachusetts Medical School, Worcester.
Pikora
C A
CA
Mazzara
G
G
Panicali
D
D
Sullivan
J L
JL
D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D001402:B-Lymphocytes; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D006678:HIV / Q000145:classification / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D011994:Recombinant Proteins / Q000276:immunology
D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins