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Patterns of Cross-clade Neutralizing Antibody Responses in HIV-1-infected Cameroonians
Y Blount1, P Foujungo1, M Kalou1, P Raghunathan1, G Alemnji1, D Montefiori2, M Callahan1, S Butera1, J Nkengasong1, and Chunfu Yang*1
1CDC, Atlanta, GA, US and 2Duke Univ Med Ctr, Durham, NC, US
Background: Neutralizing
antibody responses are a major immunologic component during viral infection and
of protective vaccinees. However, little is known about cross-clade
neutralizing antibody responses in HIV-1-infected persons in countries where
multiple subtypes, CRF, and URF are co-circulating. We investigated the
patterns of cross-clade neutralizing antibody responses in HIV-1-infected
Cameroonians.
Methods: Between March 2004 and February 2005, we collected and tested plasma samples
from 42 HIV-1-infected Cameroonian blood donors. Anti-HIV-1 neutralizing
antibodies were measured by a recombinant virus assay. We included 8 HIV-1 Env-pseudotyped
viruses: 3 were subtype C, 2 subtype B,
and 1 each of subtype A, CRF01_AE, and CRF02_AG. Neutralizing antibody titers were
defined as the plasma dilution that gave 50% reduction in single-round viral infectivity
measured by luciferase activity from indicator cells.
Results: Median CD4 count
for the 35 donors, for whom data were available, was 428 cells/mm3 (range
178 to 1532), and median log10 viral load was 4.66 copies/mL (range 2.30
to 6.11). Of the 42 plasma samples, 28 (67%) had neutralizing antibodies
against at least 1 of the 8 Env-pseudotyped viruses, and 14 (33%) had no detectable
neutralizing antibodies. Neutralizing antibody titers against the Env-pseudotyped
viruses ranged from 30 to 543. Of the 28 persons with neutralizing antibodies, 63%
had neutralizing antibodies against pseudoviruses with subtype A env sequences, 57% with subtype C env sequences, and 16% with subtype B env sequences. Of the samples, 11 (39%)
had broadly neutralizing antibodies to more than 4 of the Env-pseudotyped
viruses tested, with median IC50 titer 62, ranging from 30 to 543.
Conclusions: Our preliminary
analysis indicates that in Cameroon,
a country where multiple HIV-1 subtypes and recombinants circulate, the majority
of persons with HIV-1 infection produce cross-clade neutralizing antibodies with
some degree of reactivity against diverse primary HIV-1 strains. Thus, comprehensive
analyses of cross-clade neutralizing antibody responses may provide valuable
information on vaccine design and effective strategies in HIV prevention.
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