Induction of neutralizing antibodies in rhesus macaques using V3 mimotope peptides

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

    Research output: Contribution to journalArticle

    7 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
    Publication statusPublished - May 23 2016

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    Keywords

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

    ASJC Scopus subject areas

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

    Cite this

    Hessell, A., McBurney, S., Pandey, S., Sutton, W., Liu, L., Li, 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