3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

IMMUNOLOGICAL CORRELATES OF APPARENT PROTECTION IN EXPOSED YET HIV-1 SERONEGATIVE UGANDANS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. MoOa0402

Kebba A.¹, Imami N.², Grosskurth H.¹, Gotch F.^2
1Uganda Virus Research Institute, Entebbe, Uganda, ²Imperial College, London, United Kingdom

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 IFN-γ secretion by ELISpot.
  
• Proliferation coupled to intracellular production of IFN-γ, 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 IFN-γ 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.

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Basic | MoOa0402 | Frances Gotch

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