Genetic and immunologic characterization of viruses infecting MN-rgp120-vaccinated volunteers.
Proviral sequences were determined and immunologic characterization was carried out for envelope glycoproteins from 7 vaccinees who became infected with human immunodeficiency virus type 1 (HIV-1), through high-risk behavior, while participating in clinical trials of MN-rgp120, a candidate HIV-1 vaccine. All 7 infections resulted from subtype B viruses; however, only 3 of the viruses possessed the MN serotype-defining V3 domain sequence, IGPGRAF, prevalent in 60%-70% of US infections. Six of the 7 viruses differed from MN-rgp120 at a neutralizing epitope in the C4 domain, and all 7 differed from MN-rgp120 at a neutralizing epitope in the V2 domain. Recombinant gp120 was prepared from each breakthrough specimen and tested for binding to a panel of neutralizing monoclonal antibodies. The results suggest that 6 of 7 breakthrough infections may be related to incomplete immunization or to infection with viruses that differed from the vaccine immunogen at important virus-neutralizing epitopes.
Berman
P W
PW
Department of Process Sciences, Genentech, Inc., South San Francisco, California 94080, USA.
Gray
A M
AM
Wrin
T
T
Vennari
J C
JC
Eastman
D J
DJ
Nakamura
G R
GR
Francis
D P
DP
Gorse
G
G
Schwartz
D H
DH
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics; D014644:Genetic Variation; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D011993:Recombinant Fusion Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic