NEUTRALIZATION OF HIV-1 SUBTYPES - IMPLICATIONS FOR VACCINE FORMULATIONS

More than 20.8 million people are infected with HIV in sub-Saharan Afr ica, with South Africa having one of the fastest growing HIV-1 epidemi cs, where an estimated 2.4 million people were infected. Thirty-two se ra from 25 patients were tested for their ability to neutralize HTLV-I II, (IIIB) and four primary isolates representing subtypes B, C, D, an d a recombinant gag C/env B type. A CEM-SS cell line-based assay was u sed and the neutralizing titer was defined as the reciprocal of the hi ghest dilution giving a 50% reduction in p24 antigen production. All i solates were neutralized better by subtype-specific sera, except for t he C4714 strain, which was neutralized by both subtype B and C sera. C 4714 was neutralized by 18/25 (72%) sera, IIIB by 19/32 (59%) sera, D4 82 by 7/31(23%) sera, B3245 by 6/29 (21%) sera, and the recombinant B/ C1491 isolate by 4/25 (16%) sera. Five sera were unable to neutralize any of the isolates. The V3 region of the isolates used in the neutral ization assay was amplified by PCR, directly sequenced, and analyzed t o reveal variability between the consensus HIV-I sequences and the iso lates. HIV-1 strain C4714 was neutralized more effectively with the se ra tested than the IIIIB laboratory strain. Variability in the amino a cid sequence of the V3 region, which can alter the conformation of the V3 loop secondary structure, can influence the neutralization of a pa rticular viral isolate. Vaccine formulations should be broadened to in clude multiple subtypes, especially C subtypes, which is rapidly sprea ding worldwide. J. Med. Virol. 56:264-268, 1998. (C) 1998 Wiley-Liss, Inc.