Antibody mediated and cell mediated immune responses to the envelope
glycoproteins gp120 and gp41 of the human immunodeficiency virus (HIV-1) are considered important for protection against
infection and for attenuation of disease symptoms after
infection. Virus
neutralizing antibodies are mostly subtype specific and primarily directed against
epitopes on a hypervariable loop from the V3 region of HIV-1 gp120. Such
epitopes are recognized by helper and cytotoxic T-cells suggesting that all protective immune responses to HIV-1 are predominantly subtype specific. The extraordinary primary sequence variability of gp120 indicates that a combination of subtype specific components will be required to design a broadly effective protective immunogen against HIV-1.
Peptides from hypervariable loops of the V3 region of 21 distinct HIV-1 isolates (clones) were synthesized and used to raise rabbit
antisera. The
antisera contained high levels of
antibodies recognizing the homologous
peptides and the parent gp120 sequence. The serological cross-reactivity between the distinct
peptides was evaluated and related to
amino acid divergence. The corresponding relationship approximated a linear regression with a correlation coefficient r = 0.718. The 21
peptides were combined into a single immunogen which elicited broadly reactive
antibodies recognizing all 21
peptides as well as gp120 from the only isolate tested, HIV-1 IIIB. The results suggest the possibility of developing broadly protective HIV-1 immunogens by combining judiciously selected subtype specific
peptides derived from envelope
glycoproteins of divergent virus isolates.