Cryptic epitopes (CE) are MHC-I-restricted peptides encoded by any of the 5 alternative reading frames (ARFs) of a gene. CE-specific T cells (Tc) have previously been detected in HIV-1 infected patients but whether responses to CE can be induced by vaccination is currently unknown. Our previous work demonstrated that vaccination with naturally-encoded, non-codon optimized vectors generate CE more frequently than codon-optimized vectors. We therefore analyzed samples from 126 individuals who received either a naturally-encoded MVA/HIV62 double prime-double boost regimen (vaccine) or saline (placebo) during the HVTN205 trial. Peripheral blood mononuclear cells collected at 2 weeks post final vaccination were stimulated in an IFNγ ELISpot assay with overlapping peptide pools (OLPs) for HIV-1 Gag, Pol, and all 5 ARFs of these regions. Vaccinees had significantly more positive responses toward Gag but not Pol than placebo recipients (p=0.020, Mann-Whitney U test). Ex vivo Tc responses to potential CE were low in magnitude and their frequency did not differ significantly between treatment groups. In a cultured assay however, the median magnitude of responses to ARF OLP subpools was significantly greater in vaccinees (p< 0.001, Mann-Whitney U test), indicating CE-specific Tc responses are present but below the IFNγ ELISpot assay’s limit of detection. Thus, we recommend that future vaccines expand the breadth of HIV-1 Tc responses through designs that preserve naturally-encoded CE.
- Copyright © 2013 by The American Association of Immunologists, Inc.