Lessons from a multisite international trial in the Caribbean and South America of an HIV-1 Canarypox vaccine (ALVAC-HIV vCP1452) with or without boosting with MN rgp120.
BACKGROUND
The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial evaluated the safety and immunogenicity of a clade B-derived, live canarypox HIV vaccine, vCP1452. vCP1452 was administered alone or with a heterologous boost of MN rgp120 glycoprotein. The trial was pivotal in deciding whether these vaccines advanced to phase 3 efficacy trials.


METHODS
Forty seronegative volunteers per site were randomized to ALVAC alone, ALVAC plus MN rgp120, or placebo in a 0, 1, 3, and 6 month schedule. Immunogenicity was assayed by chromium-release cytotoxic T lymphocyte (CTL) responses; interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays (ELISpot); lymphocyte proliferation assays (LPA); neutralization; and enzyme-linked immunosorbent assays (ELISA).


RESULTS
Enrollment and follow-up were excellent. Both vaccines were well tolerated. Neutralizing antibody to the laboratory-adapted MN strain was detected. Cellular immune responses, as measured by CTL, ELISpot, and LPA, did not differ between vaccines and placebos.


CONCLUSIONS
The observation of disappointing immunogenicity in this and a parallel domestic study has informed future vaccine development. Equally important, challenges to doing an integrated trial across countries, cultures, languages, and differing at-risk populations were overcome. The identification of specific safety, ethical, logistic, and immunological issues in this trial established the foundation for current larger international studies.
Cleghorn
Farley
F
Center for HIV/AIDS, Constella Futures, Washington, DC, USA.
Pape
Jean W
JW
Schechter
Mauro
M
Bartholomew
Courtenay
C
Sanchez
Jorge
J
Jack
Noreen
N
Metch
Barbara J
BJ
Hansen
Marianne
M
Allen
Mary
M
Cao
Huyen
H
Montefiori
David C
DC
Tomaras
Georgia D
GD
Gurunathan
Sanjay
S
Eastman
Donna J
DJ
do Lago
Regina F
RF
Jean
Sonic
S
Lama
Javier R
JR
Lawrence
Dale N
DN
Wright
Peter F
PF
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D001938:Brazil; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006205:Haiti; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010568:Peru; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D014300:Trinidad and Tobago; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000097:blood / Q000276:immunology
D016915:AIDS Vaccines; C468116:ALVAC-HIV vCP1452; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C122180:MNrgp120 vaccine; D014614:Vaccines, Synthetic; D007371:Interferon-gamma