title: Enhancement of HIV type 1 vaccine immunogenicity by block copolymer adjuvants. I. Induction of high-titer, long-lasting, cross-reactive antibodies of broad isotype.
abstract: Improvements in HIV-1 vaccines are urgently needed since many of the available vaccines are weak immunogens. We examined the ability of CRL1005, a novel nonionic block copolymer adjuvant, to improve the immunogenicity of multiple HIV-1 envelope vaccines: six gp120s and single and multiple V3 peptides (MAPs). Formulation of vaccine with adjuvant, as compared with alum or saline, enhanced antibody titer in mice up to 200-fold, with antibody half-lives of >200 days. For most vaccinations, an oil-in-water formulation induced the highest antibody titers; for some antigens, however, particularly single peptides, water-in-oil (w/o) was better. Antigen cross-reactivity was optimized by formulation in w/o, while addition of detoxified lipopolysaccharide enhanced levels of IgG2a and IgG2b. After more than 1 year of observation, no vaccine-related toxicity was observed and emulsified antigen in encapsulated depots was found at immunization sites of w/o-immunized animals. No other adjuvant has been reported to induce such long-lasting antibodies, and the ability of CRL1005 to greatly amplify and qualitatively modify antibody responses suggests that it may be useful in developing improved HIV vaccines for humans.
authors.affiliation: Immunology Branch, DASLTR, NCID, CDC, Atlanta, Georgia 30333, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: McNicholl
authors.forename: K B
authors.initials: KB
authors.lastname: Bond
authors.forename: E R
authors.initials: ER
authors.lastname: Ruhadze
authors.forename: M R
authors.initials: MR
authors.lastname: Olsen
authors.forename: K
authors.initials: K
authors.lastname: Takayama
authors.forename: R L
authors.initials: RL
authors.lastname: Hunter
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D003429:Cross Reactions; D003598:Cytoskeletal Proteins / Q000276:immunology; D004338:Drug Combinations; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes; D007700:Kinetics; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011060:Poloxalene; D011108:Polymers; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D003598:Cytoskeletal Proteins; D004338:Drug Combinations; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008050:Lipid A; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010455:Peptides; D011108:Polymers; D014614:Vaccines, Synthetic; C112124:detox adjuvant; D011060:Poloxalene