Evidence as a HIV-1 Self-Defense Vaccine of Cyclic Chimeric Dodecapeptide Warped from Undecapeptidyl Arch of Extracellular Loop 2 in Both CCR5 and CXCR4☆☆☆

Abstract Novel conformation-specific antibodies were raised against a cyclic chimeric dodecapeptidyl multiple antigen peptide (cCD-MAP) constructed with a spacer-armed Gly-Asp dipeptide and two pentapeptides (S 169 -Q 170 -K 171 -E 172 -G 173 of CCR5 and E 179 -A 180 -D 181 -D 182 -R 183 of CXCR4) which are components of the undecapeptidyl arch (UPA: from R 168 to C 178 in CCR5, from N 176 to C 186 in CXCR4) of extracellular loop 2 (ECL2) in chemokine receptors (CCR5 and CXCR4). Of the antibodies raised, one monoclonal antibody, CPMAb-I (IgMκ), reacted with cCD-MAP, but not with the linear chimeric dodecapeptide-MAP. The antibody reacted with the cells separately expressing CCR5 or CXCR4, but not with those not expressing the coreceptors. Moreover, the antibody markedly suppressed infection by X4, R5, or R5X4 virus in a dose-dependent manner in a new phenotypic assay for drug susceptibility of HIV-1 using CCR5-expressing Hela/CD4 + cell clone 1–10 (MAGIC-5). Moreover, CPMAb-I interfered with LAV-1 BRU infection (m.o.i. = 0.01) of Molt4#8 cells cocultured with CPMAb-I-producing hybridoma in the transwell, and significantly interfered with neither chemotaxis nor calcium influx induced with stromal cell-derived factor 1 α (SDF-1α). Thus, the antibody raised against the cCD-MAP provides powerful protection or defense against HIV-1 infection. We therefore propose the cCD-MAP or its derivative immunogen as a novel candidate for an HIV-1 coreceptor-based self-defense vaccine.