AEGiS-11IAC: Cross-clade neutralization of HIV-1 by homologous and heterologous sera and identification of three isolates that predicts the neutralizing capacity of sera across HIV-1 clades.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Cross-clade neutralization of HIV-1 by homologous and heterologous sera and identification of three isolates that predicts the neutralizing capacity of sera across HIV-1 clades.

Int Conf AIDS 1996 Jul 7-12; 11:9 (abstract no. Mo.A.273)
Nyambi PN, Lewi P, Nkengasong J, Janssens W, Fransen K, Peeters M, Willems B, Heyndrickx L, Andries K, Ndumbe P, van der Groen G; Institute of Tropical Medicine, Antwerpen, Belgium. Fax: 32 3 247 63 33.

OBJECTIVES: To study the neutralization spectra of 14 sera and of 16 primary isolates of individuals infected with HIV-1 group M (subtype A-H) and group O. To identify a limited number of primary HIV-1 key isolates which allow to predict the neutralization spectrum of a serum.

METHODS: Serum (SNS) and isolate neutralization spectra (INS) are defined by the neutralizing antibody titers (NAT) obtained with a particular serum (isolate) on a defined set of isolates (sera). SNS and INS were assessed by mixing serial dilutions (1:10 to 1:1280) of serum with 50TCID50 of primary HIV-1 isolates and measuring p24 Ag production after 7 days in mitogen-stimulated PBMC as target cells. NAT were defined as highest serum dilution that produced less than or equal to 50 and less than or equal to 90% p24 Ag inhibition. The neutralization data were analysed by the spectral map analysis.

RESULTS: Cross-clade neutralization of both HIV-1 group M and O was observed. Spectral map analysis allowed us to cluster sera and isolates by the homology of their neutralization spectrum. This analysis revealed 8 SNS and INS clusters which did not correlate with the known genetic clades. Furthermore, 3 key HIV-1 isolates were identified which allowed to predict the NAT of each of the 14 sera to the remaining 13 HIV-1 isolates. The correlation between the predicted and experimental SNS was 0.90. This observation was further validated by spectral map analysis of NAT obtained by a second set of 7 sera on the 3 key HIV-1 isolates.

CONCLUSION: Our results clearly demonstrates that SNS and INS clusters do not correlate with genetic clades. Our method of analysis will facilitate the evaluation as well as the design of suitable HIV-1 vaccines that induce high-titer inter-clade cross-neutralizing antibodies.

Keywords: AEGIS, HIV-1, AIDS Vaccines, ICA11

960707
MoA273