Optimal antigens for HIV vaccines based on CD8+ T response, protein length, and sequence variability.
The identification of optimal antigens to include in an HIV vaccine designed to elicit a cellular immune response requires careful consideration of protein length, variability, and immunogenicity. Here, we have examined the relationship of these parameters in a cohort of HIV-infected subjects. We find that HIV Gag and Nef represent optimal antigens for the CD8+ T cell response, based on size, variability, and immunogenicity. Although the Env and Pol proteins have a poorer response to length (Pol) or variability (Env) ratio than Gag or Nef, they are still strong candidates for inclusion into an HIV vaccine, based on overall response frequency in the cohort. The accessory proteins Tat, Rev, Vif, Vpr, and Vpu in general all elicit very low CD8+ T cell responses, and this, in combination with their high variability, makes them less attractive as vaccine antigen.
Betts
Michael R
MR
Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
Yusim
Karina
K
Koup
Richard A
RA
D016915:AIDS Vaccines / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D015683:Gene Products, gag / Q000276:immunology*; D015693:Gene Products, nef / Q000276:immunology*; D014644:Genetic Variation; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000941:Antigens; D015683:Gene Products, gag; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma