Differences Between T Cell Epitopes Recognized After Immunization and After Infection

Abstract

Evidence suggests that cellular immune responses play a crucial role in the control of HIV and SIV replication in infected individuals. Several vaccine strategies have therefore targeted these CD8+ and CD4+ responses. Whether vaccination induces the same repertoire of responses seen after infection is, however, a key unanswered question in HIV vaccine development. We therefore compared the epitope specificity induced by vaccination to that present postchallenge in the peripheral blood. Intracellular cytokine staining of PBMC stimulated with overlapping 15/20-mer peptides spanning the proteins of SIV were measured after DNA/modified vaccinia Ankara vaccination of eight rhesus macaques. Lymphocytes from 8 animals recognized a total of 39 CD8 epitopes and 41 CD4 epitopes encoded by the vaccine. T cell responses were again monitored after challenge with SIVmac239 to investigate the evolution of these responses. Only 57% of all CD8+ T cell responses and 19% of all CD4+ T cell responses present after vaccination were recalled after infection as measured in the peripheral blood. Interestingly, 29 new CD8 epitopes and 5 new CD4 epitopes were recognized by PBMC in the acute phase. These new epitopes were not detected after vaccination, and only some of them were maintained in the chronic phase (33% of CD8 and no CD4 responses). Additionally, 24 new CD8 epitopes and 7 new CD4 epitopes were recognized by PBMC in the chronic phase of infection. The repertoire of the immune response detected in the peripheral blood after immunization substantially differed from the immune response detected in the peripheral blood after infection.

Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques

“…Following SIVmac239 challenge, fewer potentially important subdominant epitopes were detected by our IFN-␥ ELISPOT screening compared to the frequency observed postvaccination (data not shown) (43). The epitopic breadth in animals with lower virus loads may have been underestimated by the use of peptide pools for initial screening or the high dose of virus initially used in the challenge inoculum.…”

Persistent Recognition of Autologous Virus by High-Avidity CD8 T Cells in Chronic, Progressive Human Immunodeficiency Virus Type 1 Infection

“…If this is true, then it is significant for vaccine and immunotherapy trials. These trials aim at inducing functional CD8 T-cell responses and mainly utilize gamma interferon Elispot or intracellular cytokine assays to screen for responses (16,21,29,40,50). The data presented here suggest rethinking this approach.…”

The Major Histocompatibility Complex Class II AllelesMamu-DRB1*1003and -DRB1*0306Are Enriched in a Cohort of Simian Immunodeficiency Virus-Infected Rhesus Macaque Elite Controllers

“…Few SIV-specific CD4 ϩ T-cell responses have been reported to date (12,24,38,54), and there is even less information about the MHC-II alleles that restrict SIV epitopes recognized by Indian rhesus macaque CD4 ϩ T cells (12,24). In this study, we mapped several SIV-specific CD4 ϩ T-cell epitopes ( Fig.…”