AEGiS-13IAC: Investigation of cross-clade cellular immune responses in Ugandan patients infected with non-clade B HIV-1 by the ELISPOT assay.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Investigation of cross-clade cellular immune responses in Ugandan patients infected with non-clade B HIV-1 by the ELISPOT assay.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrA594)

Rutebemberwa A, Auma B, Gillmour J, Jones G, Watera C, Imami N, Kaleebu P, Whitworth J, Gotch F
A. Rutebemberwa, Uganda Virus Research Institute, P. O. Box 49, Entebbe, Uganda, Tel.: +256-41-320272/320042, Fax: +256-41-321137, E-mail: mrc@starcom.co.ug

BACKGROUND: An effective HIV vaccine should induce good cross-clade cellular immune responses. In order to prepare for future vaccine trials, there is need to investigate the extent of cross-clade immune responses in HIV-1 infected persons, and to develop simple and rapid assays to study cellular immunity.

METHODS: A cohort of 50 HIV-1 infected persons was established in Entebbe, Uganda. Infecting clades were determined by env HMA and gag sequencing is underway. All persons were HLA tissue typed by SSP-PCR. Longitudinal and cross-clade cellular immune responses have been investigated by peptide and vaccinia Elispot assays.

RESULTS: The MHC class I molecules common in the cohort are HLA A (38%), A29 (14%), A30 (38%),B58( 33%), B45(17%), and B57 (17%). In 21 persons in whom viral subtypes were determined by env HMA, 11 were clade A, 9 were clade D and 1 was clade C. The following peptides were found to induce the highest T-cell responses: A2 restricted p17 gag peptides SLYNTVATL derived from clade B(LAI) and D, and SLFNTVATL derived from clade A; B57 restricted gag peptides ISPRTLNAW derived from LAI/D, LSPRTLNAW derived from clade A and TSTLQEQIGW derived from LAI/D. Most patients recognised peptide constructs derived from subtypes other than their own subtype. Consistent hierarchies of recognition were observed in peptide responses in 4/6 persons. 50% of 27 persons (5 not tissue typed) responded to vaccinia expressing gag, pol or env constructs of HIV-1 MN, IIIB, A or D.

CONCLUSION: We have shown that cross-clade cellular immune responses exist in HIV-1 infected persons, however dominant peptide recognition is apparent. Elispot assays are a simple, rapid assays that can be used in large studies of HLA typed subjects, in addition vaccinia Elispot assays can be used successfully in non-tissue typed subjects to measure global responses to HIV antigens expressed by rVV.

Keywords: AEGIS, HIV-1, HIV Antigens, AIDS Vaccines, Enzyme-Linked Immunosorbent Assay, HLA Antigens, Uganda, Human, immunology
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