title: 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.
abstract: 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.
authors: Center for HIV/AIDS, Constella Futures, Washington, DC, USA.
authors: Farley
authors: F
authors: Cleghorn
authors: Jean W
authors: JW
authors: Pape
authors: Mauro
authors: M
authors: Schechter
authors: Courtenay
authors: C
authors: Bartholomew
authors: Jorge
authors: J
authors: Sanchez
authors: Noreen
authors: N
authors: Jack
authors: Barbara J
authors: BJ
authors: Metch
authors: Marianne
authors: M
authors: Hansen
authors: Mary
authors: M
authors: Allen
authors: Huyen
authors: H
authors: Cao
authors: David C
authors: DC
authors: Montefiori
authors: Georgia D
authors: GD
authors: Tomaras
authors: Sanjay
authors: S
authors: Gurunathan
authors: Donna J
authors: DJ
authors: Eastman
authors: Regina F
authors: RF
authors: do Lago
authors: Sonic
authors: S
authors: Jean
authors: Javier R
authors: JR
authors: Lama
authors: Dale N
authors: DN
authors: Lawrence
authors: Peter F
authors: PF
authors: Wright
mesh_terms: 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
chemical_list: D016915:AIDS Vaccines; C468116:ALVAC-HIV vCP1452; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C122180:MNrgp120 vaccine; D014614:Vaccines, Synthetic; D007371:Interferon-gamma