Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein.
In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus. The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees. Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively). In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e. T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable. The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both. Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals. If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.
Cooney
E L
EL
Department of Laboratory Medicine, University of Washington, Seattle.
Collier
A C
AC
Greenberg
P D
PD
Coombs
R W
RW
Zarling
J
J
Arditti
D E
DE
Hoffman
M C
MC
Hu
S L
SL
Corey
L
L
D000328:Adult; D004279:DNA, Viral / Q000032:analysis; D004306:Dose-Response Relationship, Immunologic; D004341:Drug Evaluation; D005500:Follow-Up Studies; D015686:Gene Products, env / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000032:analysis*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D011498:Protein Precursors / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D011537:Pruritus / Q000209:etiology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D004279:DNA, Viral; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D014614:Vaccines, Synthetic; D014765:Viral Vaccines