Induction of neutralizing antibodies in rhesus macaques using V3 mimotope peptides

Ann J. Hessell, Sean McBurney, Shilpi Pandey, William Sutton, Lily Liu, Liuzhe Li, Maxim Totrov, Susan Zolla-Pazner, Nancy L. Haigwood, Miroslaw K. Gorny

    Research output: Contribution to journalArticle

    9 Scopus citations

    Abstract

    RV144 vaccinees with low HIV-1 Envelope-specific IgA antibodies (Abs) also had Abs directed to the hypervariable region 3 (V3) that inversely correlated with infection risk. Thus, anti-V3 HIV-1 Abs may contribute to protection from HIV-1 infection. The V3 region contains two dominant clusters of epitopes; one is preferentially recognized by mAbs encoded by VH5-51 and VL lambda genes, while the second one is recognized by mAbs encoded by other VH genes. We designed a study in rhesus macaques to induce anti-V3 Abs specific to each of these two dominant clusters of V3 epitopes to test whether the usage of the VH5-51 gene results in different characteristics of antibodies. The two C4-V3 immunogens used for immunization were each comprised of a fusion of the C4 peptide containing the T cell epitope and a V3 mimotope peptide mimicking the V3 epitope. The C4-447 peptide was designed to target B cells with several VH1-VH4 genes, the C4-VH5-51 peptide was designed to specifically target B cells with the VH5-51 gene. Six animals in two groups were immunized five times with these two immunogens, and screening of 10 sequential plasma samples post immunization demonstrated that C4-447 induced higher titers of plasma anti-V3 Abs and significantly more potent neutralizing activities against tier 1 and some tier 2 pseudoviruses than C4-VH5-51. Levels of anti-V3 Abs in buccal secretions were significantly higher in sequential samples derived from C4-447- than from C4-VH5-51-immunized animals. The titers of anti-V3 Abs in plasma strongly correlated with their levels in mucosal secretions. The results show that high titers of vaccine-induced anti-V3 Abs in plasma determine the potency and breadth of neutralization, as well as the rate of transduction of Abs to mucosal tissues, where they can play a role in preventing HIV-1 infection.

    Original languageEnglish (US)
    Pages (from-to)2713-2721
    Number of pages9
    JournalVaccine
    Volume34
    Issue number24
    DOIs
    StatePublished - May 23 2016

    Keywords

    • HIV vaccine
    • HIV-1
    • HIV-1 neutralizing antibodies
    • Non-human primates immunization
    • Rhesus macaque immunoglobulin genes
    • V3 immunogens

    ASJC Scopus subject areas

    • Molecular Medicine
    • Immunology and Microbiology(all)
    • veterinary(all)
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

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  • Cite this

    Hessell, A. J., McBurney, S., Pandey, S., Sutton, W., Liu, L., Li, L., Totrov, M., Zolla-Pazner, S., Haigwood, N. L., & Gorny, M. K. (2016). Induction of neutralizing antibodies in rhesus macaques using V3 mimotope peptides. Vaccine, 34(24), 2713-2721. https://doi.org/10.1016/j.vaccine.2016.04.027