Comparison of the immune response to recombinant gp120 in humans and chimpanzees.
OBJECTIVE
To assess similarities and differences in antibody responses to recombinant (r) HIV-1IIIB gp120 in chimpanzees, previously protected from HIV-1 infection, and human volunteers immunized in connection with a Phase I clinical trial.


METHODS
Frozen sera from humans immunized with rgp120 from HIV-1IIIB and chimpanzees immunized with the same antigen or recombinant soluble gp160 were compared in a variety of serologic assays.


RESULTS
The magnitude of the antibody response to gp120 was similar in both species; however, the half-life of the antibody response to rgp120 was approximately 4.5 times longer in humans (9 weeks) than in chimpanzees (2 weeks). Antibodies to gp120 in both species were broadly cross-reactive with gp120 from diverse isolates of HIV-1 and were effective in blocking the binding of gp120 to CD4. Antibody binding to native gp120 was greater than to denatured gp120 in both species. Antibody responses to the principal neutralizing determinant (V3 domain) and virus neutralization titers were approximately 10-fold lower in humans than chimpanzees. The relative avidity of antibody binding to gp120 was higher in the sera from the immunized chimpanzees than in the immunized humans.


CONCLUSIONS
While the antibody responses to rgp120 elicited in man and chimpanzees were in many ways similar, significant differences did occur. Predictions made on the basis of chimpanzee immunogenicity studies over-estimated the potency of the virus neutralizing titers and under-estimated the duration of the antibody response achieved in humans.
Berman
P W
PW
Department of Immunology, Genentech Inc., South San Francisco, California 94080.
Eastman
D J
DJ
Wilkes
D M
DM
Nakamura
G R
GR
Gregory
T J
TJ
Schwartz
D
D
Gorse
G
G
Belshe
R
R
Clements
M L
ML
Byrn
R A
RA
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D002679:Pan troglodytes / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000276:immunology*; D013045:Species Specificity; D014611:Vaccination
D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D011994:Recombinant Proteins