Augmentation of human immunodeficiency virus type 1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160 in vaccinia-naive adults. The NIAID AIDS Vaccine Clinical Trials Network.
Twelve vaccinia-naive volunteers were inoculated with recombinant vaccinia virus expressing the human immunodeficiency virus type 1 (HIV-1) strain IIIB (HIV-1IIIB) envelope glycoprotein gp160 and subsequently immunized with 640 micrograms of recombinant (r) gp160 protein produced in baculovirus. After booster immunization with rgp160, the sera of all vaccinees showed strong antibody responses detected by Western blot and ELISA; 8 had neutralizing activity and 5 had fusion inhibition activity against the homologous strain; 5 blocked binding of CD4 cells to gp120. Cross-reactive neutralization of HIV-1MN was detected in 3 of 8 sera that neutralized HIV-1IIIB. The combination of live recombinant vaccinia followed by subunit booster immunization was more immunogenic than either product alone and represents a promising approach for HIV-1 immunoprophylaxis. Further definition of recombinant vaccinia safety and augmentation of immune responses to geographically prevalent HIV-1 strains will be necessary before expanding clinical trials to high-risk groups.
Graham
B S
BS
Dept. of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
Matthews
T J
TJ
Belshe
R B
RB
Clements
M L
ML
Dolin
R
R
Wright
P F
PF
Gorse
G J
GJ
Schwartz
D H
DH
Keefer
M C
MC
Bolognesi
D P
DP
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000096:biosynthesis / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D011498:Protein Precursors / Q000096:biosynthesis / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013997:Time Factors; D014616:Vaccinia virus / Q000276:immunology
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; C059762:HIV envelope protein gp120 (305-321); C067702:HIVAC-1e; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins