title: Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: possible role of the prolonged half-life of the immunogen.
abstract: The elicitation of broadly cross-reactive HIV-1 neutralizing antibodies in humans remains a major challenge in developing a viable AIDS vaccine. We hypothesized that prolonged exposure to candidate vaccine immunogens could enhance the elicitation of such antibodies. In an attempt to develop HIV-1 vaccine immunogens with prolonged half-lives and increased stability, we constructed a fusion protein, gp41Fc, in which a truncated HIV-1 gp41(89.6) was fused to a human IgG(1) Fc. Gp41Fc is stable in solution, retains its antigenic structure and is highly immunogenic in rabbits. The serum titers reached 1:102,400 for the gp41Fc and 1:5,120 for gp140(89.6). Rabbit IgG neutralized diverse HIV-1 isolates and HIV-2, and the neutralization activity was attributed to gp41-specific IgG. The concentration of the gp41Fc in the serum correlated with the neutralization activity of rabbit IgG which recognized mostly conformation-independent epitopes on gp41 and predominantly bound to peptides derived from the gp41 immunodominant loop region. These results suggest that the prolonged half-life of gp41Fc in the serum may enhance the generation of cross-reactive neutralizing antibodies. Further research is needed to confirm and extend these results which may have implications for the development of vaccine immunogens with enhanced capability to elicit cross-reactive HIV-1-neutralizing antibodies.
authors.affiliation: Center for Cancer Research Nanobiology Program, CCR, NCI-Frederick, NIH, Frederick, MD 21702, USA. meiyun_zhang@yahoo.com
authors.forename: Mei-Yun
authors.initials: MY
authors.lastname: Zhang
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Marie K
authors.initials: MK
authors.lastname: Mankowski
authors.forename: Roger G
authors.initials: RG
authors.lastname: Ptak
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology* / Q000493:pharmacokinetics*; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology; D006207:Half-Life; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000494:pharmacology*; D009500:Neutralization Tests; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; C514787:gp41 protein, Human immunodeficiency virus 1