Neutralizing antibody induced in mice by novel glycoconjugates of human immunodeficiency virus type 1 gp120 and env2-3.
We sought to determine whether conjugation methods could improve the immunogenicity of human immunodeficiency virus (HIV)-1 gp120 and env2-3, a nonglycosylated form of gp120. Conjugate vaccines were created by coupling tetanus toxoid (TT), gp120, and/or env2-3 with group B streptococcal type III polysaccharide (III) by reductive amination. Size-exclusion chromatography revealed polymers larger than those of the uncoupled proteins after conjugation. Geometric mean titers of gp120-specific immunoglobulin G (IgG) in serum from mice given env2-3-TT-III or env2-3-gp120-TT-III conjugates increased from <50 before to 3031 and 4756, respectively, after vaccination, whereas an uncoupled mixture of gp120, TT, and III, and III-TT not coupled with gp120 or env2-3 were poorly immunogenic. Pooled serum diluted 1rcolon;20 from mice given env2-3-gp120-TT-III inhibited infection of HIV-1(MN) of Sup-T1 cells and demonstrated neutralizing activity against infection with primary isolate HIV-1(BR014). HIV-1 gp120-specific IgG with neutralizing activity against HIV-1 can be induced with conjugates containing gp120, env2-3, III, and TT.
Paoletti
Lawrence C
LC
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. lpaoletti@channing.harvard.edu
Kennedy
Ronald C
RC
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015686:Gene Products, env / Q000276:immunology*; D006001:Glycoconjugates / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011135:Polysaccharides, Bacterial / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
D016915:AIDS Vaccines; D015686:Gene Products, env; D006001:Glycoconjugates; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C032263:streptococcal polysaccharide type III group B