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Abstract
Immunological correlates of apparent protection in exposed yet HIV-1 seronegative Ugandans.
Kebba A.1, Imami N.2, Grosskurth H.1, Gotch F.2
Introduction: It is becoming increasingly evident that sero-conversion may not be the inevitable outcome of repeated exposure to HIV. Apparent protection to HIV-1 infection may be due to a multiplicity of factors including genetic polymorphisms and innate and acquired cellular and humoral HIV-1 specific immune responses.
Methods: HIV-1 sero-discordant monogamous couples in Uganda with a median duration of union of 10.5 years and a history of unprotected sex were enrolled. The following were evaluated in the seropositive (SP) and exposed seronegative (ESN) partners: • HIV-1-specific antibodies in mucosal and systemic compartments. • Expression of CD91 on CD14+ monocytes. • HLA class I tissue types. • Recognition by CD8+T cells of HIV-1 peptides quantitating IFNg secretion by ELISpot. • Proliferation coupled to intracellular production of IFNg, IL-2, IL-4 and IL-2, perforin in HIV-1 specific CD4+ and CD8+ T cells respectively.
Results: • In ESN cross-clade HIV-1 gp160-specific IgA and/or IgG antibodies were present in genital secretions but absent in plasma. • Monocytes of ESN had significantly higher CD91 surface expression than those of SP or unexposed low-risk persons. • The Cw*06 allele and the B*58-Cw*06 haplotype were over-expressed in ESN compared to SP. • Quantitation of HIV-1-specific IFNg responses suggested preferential HIV-1 peptide recognition between SP and ESN, with ESN recognising peptides previously associated with slow progression of HIV-1 infection, and SP recognising peptides from relatively conserved regions. • Flow cytometric analysis in showed maintenance of cytokine function in ESN and SPs, but proliferative dysfunction in both CD4+ and CD8+ subsets in SP.
Conclusions: HIV-1 specific humoral and cellular immune responses in ESN may play an important role in protecting vulnerable persons from HIV-1 infection, and such responses should be induced by prophylactic vaccines.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
MoOa0402
Suggested Citation
"KebbaA., et al.
Immunological correlates of apparent protection in exposed yet HIV-1 seronegative Ugandans..
Oral Abstract Sessions:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
MoOa0402"
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