14th International AIDS Conference


Barcelona, Spain - July 7-12, 2002

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HIV neutralisation revisited: Slow disease progression associated with cross-neutralising activity and neutralisation escape.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10077)

Fenyo EM, Shi Y, Karlsson A, Leitner T, Albert J
MMDI, Lund University, Lund, Sweden

BACKGROUND: Studies on the role of neutralising antibodies in human immunodeficiency virus type 1 (HIV-1) infection were limited by the lack of simple assays for HIV-1 neutralisation. We have developed a plaque reduction assay based on syncytia formation of HIV-1 primary isolates in a human cell line engineered to express CD4 and the CCR5 co-receptor. We examined autologous as well as heterologous neutralisation by sequentially obtained sera from four HIV-1 infected individuals who showed slow clinical progression and harboured CCR5-using virus.

METHOD: Appropriate dilutions of sera and virus were mixed, incubated for an hour at 37 °C and, subsequently, serially diluted in 5-fold steps onto U87.CD4-CCR5 cells. Cultures were fixed and stained with heamatoxylin and plaques (distinct groups of syncytial cells) enumerated by light microscopy. Plaque reduction was calculated relative to virus diluted in absence of serum.

RESULTS: In the autologous system, the early serum neutralised less well an isolate obtained 3-5 years later (late isolate) than a concurrently obtained isolate (early isolate), suggestive of neutralisation escape. In the heterologous reaction, the same early sera neutralised early and late isolates obtained from other individuals with similar efficiency. Tests with subsequently collected sera are in progress.

CONCLUSION: The results show that during slow clinical progression and in apparent absence of co-receptor evolution, the patients' sera are capable of cross-neutralising several primary isolates. Neutralisation escape can be demonstrated on the level of the HIV-1 infected individual, in that, viruses with increased resistance to neutralisation with the patient's own serum emerge over time.

Keywords: AEGIS, Disease Progression, HIV Infections, HIV Seropositivity, HIV-1, Receptors, CCR5, Antigens, CD4, CD4-Positive T-Lymphocytes, Plaque Assay, Greece, Human, immunologyKWDaegis,diseaseprogression,hivinfections,hivseropositivity,hiv-1,receptors,ccr5,antigens,cd4,cd4-positivet-lymphocytes,plaqueassay,greece,human,immunology

020707
A10077

Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.