Document Detail


Enhancement of HIV type 1 vaccine immunogenicity by block copolymer adjuvants. I. Induction of high-titer, long-lasting, cross-reactive antibodies of broad isotype.
MedLine Citation:
PMID:  9824324     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
J M McNicholl; K B Bond; E R Ruhadze; M R Olsen; K Takayama; R L Hunter
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  14     ISSN:  0889-2229     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1999-01-28     Completed Date:  1999-01-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1457-71     Citation Subset:  IM; X    
Affiliation:
Immunology Branch, DASLTR, NCID, CDC, Atlanta, Georgia 30333, USA.
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MeSH Terms
Descriptor/Qualifier:
AIDS Vaccines / immunology*
Adjuvants, Immunologic*
Amino Acid Sequence
Animals
Cross Reactions
Cytoskeletal Proteins / immunology
Drug Combinations
Female
HIV Antibodies / immunology*
HIV Envelope Protein gp120 / immunology*
HIV-1 / immunology*
Humans
Immunoglobulin G / immunology
Immunoglobulin Isotypes
Kinetics
Lipid A / analogs & derivatives,  immunology
Lipopolysaccharides / immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Molecular Sequence Data
Peptide Fragments / immunology*
Peptides / immunology
Poloxalene*
Polymers
Time Factors
Vaccines, Synthetic / immunology*
Grant Support
ID/Acronym/Agency:
U01-AI33231-01/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/AIDS Vaccines; 0/Adjuvants, Immunologic; 0/Cytoskeletal Proteins; 0/Drug Combinations; 0/HIV Antibodies; 0/HIV Envelope Protein gp120; 0/HIV envelope protein gp120 (305-321); 0/Immunoglobulin G; 0/Immunoglobulin Isotypes; 0/Lipid A; 0/Lipopolysaccharides; 0/Peptide Fragments; 0/Peptides; 0/Polymers; 0/Vaccines, Synthetic; 0/detox adjuvant; 9003-11-6/Poloxalene

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