title: Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters.
abstract: BACKGROUND
  One of the major obstacles in the design of an effective vaccine against HIV-1 is the hypervariability of the HIV-1 envelope glycoprotein. Most HIV-1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV-1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV-1. We compared and evaluated the immunogenicity of HIV-1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV-1 isolates in immunized hamsters.
  
  
  RESULTS
  We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO) cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/E CONCLUSION: Although the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120) resulted in a quantitative improvement in vaccine-induced immunity.
authors.affiliation: Infectious Disease and Vaccine Research Centre, Research Institute Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada. aliazizi@variationbiotech.com <aliazizi@variationbiotech.com>
authors.forename: Ali
authors.initials: A
authors.lastname: Azizi
authors.forename: David E
authors.initials: DE
authors.lastname: Anderson
authors.forename: Masoud
authors.initials: M
authors.lastname: Ghorbani
authors.forename: Katrina
authors.initials: K
authors.lastname: Gee
authors.forename: Francisco
authors.initials: F
authors.lastname: Diaz-Mitoma
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D016466:CHO Cells; D049109:Cell Proliferation; D006224:Cricetinae; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007114:Immunization; D008297:Male; D008647:Mesocricetus / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010802:Phylogeny; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120