Induction of neutralizing antibodies in rhesus macaques using V3 mimotope peptides. Issue 24 (23rd May 2016)

• Record Type: Journal Article
• Authors: Hessell, Ann J.; McBurney, Sean; Pandey, Shilpi; Sutton, William; Liu, Lily; Li, Liuzhe; Totrov, Maxim; Zolla-Pazner, Susan; Haigwood, Nancy L.; Gorny, Miroslaw K.
• Is Part Of: Vaccine. Volume 34:Issue 24(2016)
• Page Start: 2713
• Page End: 2721
• Publication Date: 2016-05-23
• Subjects: HIV-1 -- HIV vaccine -- HIV-1 neutralizing antibodies -- V3 immunogens -- Non-human primates immunization -- Rhesus macaque immunoglobulin genes; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.04.027
• Languages: English
• ISSNs: 0264-410X

Abstract

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.