12th International AIDS Conference Geneva, Switzerland - June 28-July 3, 1998

Int Conf AIDS 1998 Jun 28-Jul 3; 12:18 (abstract no. 11178)

Nyanbi PN, Gorny MK, Bastiani L, Williams C, Zolla-Pazner S
New York University Medical Center, V.A. Hospital, New York 10010, USA.

OBJECTIVE: To determine the ability of monoclonal antibodies (mAbs) to bind to intact HIV-1 virions of different clades in a newly developed virus-binding assay.

MATERIALS AND METHODS: Fourteen human mAbs derived from HIV-1-infected persons were used, including five to the V3 loop, three to the CD4 binding domain (CD4bd), and two each to V2, C5 and gp41. Anti-HIV-1 pooled immunoglobulin (HIVIG) from infected persons was used as a positive control. Culture supernatants from normal, PHA-stimulated peripheral blood mononuclear cells infected with HIV-1 primary isolates were used as the source of virus. Nine isolates were used, four from clade B and one each from clades A, D, F, G and H. The Abs were coated onto microtiter wells followed by addition of virus. Bound virus was detected after lysis by testing for p24 antigen with a non-commercial p24 ELISA.

RESULTS: HIVIG bound all the isolates tested, irrespective of clades. Similarly, the anti-C5 mAbs bound isolates of all the clades tested suggesting that the C5 region is well-exposed on the viral surface. The anti-V3 mAbs strongly bound the four clade B viruses tested and bound viruses from the non-B clade tested although binding was weaker and more sporadic than with clade B strains. Binding by anti-V3 mAbs did not distinguish between CXCR4- and CCR5-tropic viruses, suggesting that the V3 loops of these two categories of viruses are similarly exposed on the surface of these virions. Only weak and sporadic binding of all viruses was detected with anti-CD4bd, anti-V2, and anti-gp41 mAbs.

CONCLUSION: Using a new virus-binding assay, isolates of different clades were shown to share conserved antigenic epitopes. Of the epitopes studied that are exposed on the virus surface, C5 appears to be the most conserved among clades. V3 is exposed on the surface of both CXCR4- and CCR5-tropic viruses and some V3 epitopes are shared across clades. Several epitopes in the CD4bd, V2 and gp41 are not exposed on the viral surface.

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