Journal of Biomedical Science

, Volume 5, Issue 3, pp 192–202 | Cite as

Generation of HIV-1/HIV-2 cross-reactive peptide antisera by small sequence changes in HIV-1 reverse transcriptase and integrase immunizing peptides

  • Michael Klutch
  • Amy M. Woerner
  • Carol J. Marcus-Sekura
  • Judith G. Levin
Original Paper
Received:
Accepted:

Abstract

We have generated peptide antisera against selected regions in HIV-1 and HIV-2 reverse transcriptase (RT) and integrase (IN) to investigate the specificity of determinants governing the immune response. Peptides representing homologous regions (>50%) in the N- and C-termini and central portions of these proteins were synthesized and injected into rabbits. HIV-1 and HIV-2 IN peptide antisera inhibited IN-mediated cleavage of an HIV-1 DNA oligo-nucleotide substrate in a 3′ processing assay, while anti-RT or normal sera had no effect. None of the RT sera inhibited RT activity. In Western blots, HIV-2 antisera directed against RT or IN peptides recognized HIV-2 RT and IN proteins, respectively, as expected, but also cross-reacted with the corresponding HIV-1 proteins. By contrast, corresponding HIV-1 antisera were type-specific. In some cases, HIV-1 cross-reactive antisera could be generated by immunization with HIV-1 chimeric peptides with as few as two residues in the HIV-1 sequence changed to the corresponding HIV-2 amino acids. The finding that a type-specific response can be converted to a cross-reactive response suggests alternate strategies for developing new diagnostic reagents which detect HIV-1 and HIV-2. In addition, our results provide a general model for generating HIV peptide vaccines with dual specificity against HIV-1 and HIV-2.

Key Words

HIV-1 HIV-2 Synthetic peptides Peptide antisera Cross-reactive response Chimeric peptides Reverse transcriptase Integrase Enzyme assays Peptide diagnostics 
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Copyright information

© National Science Council 1998

Authors and Affiliations

  • Michael Klutch
    • 1
  • Amy M. Woerner
    • 1
  • Carol J. Marcus-Sekura
    • 1
  • Judith G. Levin
    • 2
  1. 1.Division of Viral ProductsCenter for Biologics Evaluation and Research, Food and Drug AdministrationBethesdaUSA
  2. 2.Laboratory of Molecular GeneticsNational Institute of Child Health and Human Development, National Institutes of HealthBethesdaUSA

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