Confronting the hypervariability of an immunodominant epitope eliciting virus neutralizing antibodies from the envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1)

• Published in: Molecular immunology Vol. 27; no. 6; p. 539
• Main Authors: Neurath, A R, Strick, N
• Format: Journal Article
• Language: English
• Published: England 01.06.1990
• Subjects: Amino Acid Sequence; Blotting, Western; Cross Reactions; Epitopes; HIV Antibodies - immunology; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp41 - immunology; HIV-1 - immunology; Molecular Sequence Data; Neutralization Tests; Peptide Fragments - immunology; Recombinant Proteins - immunology
• ISSN: 0161-5890
• DOI: 10.1016/0161-5890(90)90073-9

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.