P24.03
Background: Virus-specific CD8 T cell responses to epitopes restricted by HLA-B*35:01 are generally believed to be ineffective in mediating in vivo control of HIV infection. We report a case of a patient homozygous for HLA-B*35:01 who showed successful viral control after vaccination with MVA-B vaccine combined with a drug to reactivate HIV-1 replication (disulfiram), and who subsequently underwent an analytical treatment interruption (ATI).
Methods: Therapeutic vaccination consisted of 3 intramuscular injections of MVA-B at 0,4,16 weeks and a 4th dose followed by 2 months of disulfiram. cART was discontinued 8 weeks after last vaccination. IFN-γ ELISPOT was used to assess immunogenicity and proviral reservoir was determined over time. Viral rebound dynamics were assessed during ATI.
Results: The patient had a past history of high viral load set point (362,000 copies/ml) and cART was initiated during chronic infection. After ATI the patient remained with low level viral load<200 copies/ml for>24 weeks without showing a significant decay in CD4 T-cell counts. At baseline, the patient showed a broad (19 different specificities) and strong (9,189 SFC/106PBMC) T cell response, which increased to 14,470 SFC/106PBMC after three vaccinations. Responses to three novel T-cell epitopes present in the vaccine insert (Nef A*03-QK10, Gag A*03-RK9 and Pol B*35-VY10) were induced upon 3 vaccination. A dominant HLA-B*35:01 restricted response to the Gag-p24 B*35-PY9 epitope (PPIPVGDIY) of 3,330 SFC/106PBMC was detected before ATI. No changes in proviral reservoir or viral expression (mRNA) were observed in CD4+ T-cells after disulfiram treatment.
Conclusions: The expansion of a dominant response towards the HLA-B*35- restricted Gag RY9 epitope could potentially explain the observed viral control on this subject suggesting that certain HLA-B*35:01 restricted responses may have the potential to significantly contribute to viral control, providing important guidance for vaccine immunogen design covering non-beneficial HLA alleles.
