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Pol Epitope Map
||VID417: A*03:01, A*30:04, B*35:01, B*50:01, C*04:01, C*06:02, DQB1*02, DQB1*05, DRB1*01:01, DRB1*07:01, DRB4
||CD4 T-cell Elispot - IFNγ, Intracellular cytokine staining
||vaccine-induced immune responses, CD4+ CTL
||non-replicating adenovirus, polyepitope, DNA prime with modified vaccinia Ankara (MVA) boost, HIVconsv
||A clade, B clade, multiple epitope immunogen, C clade, D clade
||Env, Gag, Pol, Vif, other
- HIVconsv vaccine consists of 14 highly conserved regions of HIV-1 Gag, Pol, Vif, Env across clades A, B, C and D. Two vaccine regimens, CM or DDDCM, (ChAdV — ChAdV63.HIVconsv; MVA — MVA.HIVconsv; DNA - pSG2.HIVconsv) were used in the HIV-CORE 002 trial comprising HIV-negative, low-risk individuals. 199 15-mer peptides overlapping by 11 amino acids, which spanned the entire HIVconsv protein were used to interrogate PBMC from subjects, 11 of whom responded in CD4+ T cell EliSpot screenings. Truncation studies of specific epitopes suggested that the peptide length and sequence variation (altered peptide ligands) can determine whether a peptide elicits a full (agonist) or partial (partial agonist) activation phenotype or inhibitory (antagonist) CD4+ T-cell response to a stimulatory peptide epitope. Delivery of HIVconsv out of the context of the whole virus by this potent vaccine regimen revealed many novel T-cell epitopes not previously identified due to subdominant responses and thus not recorded in the Los Alamos Immunology HIV database before.
- Volunteer ID 417 (DBR1*01:01, DRB1*07:01) had a stimulatory response to VPLDEGFRKYTA (VA12/HC078E), 15-mer YFSVPLDEGFRKYTA as well as shorter peptides, FSVPLDEGFRKYTA (HC078A), SVPLDEGFRKYTA (HC078C), YFSVPLDEGFRKY (HC078D), and PLDEGFRKYTA (HC078G). In addition to IFN-γ, TNF-α was also produced. VA12 was the strongest IFN-γ stimulating peptide and PA11, the weakest, producing substantial TNF-α, indicating that these are potentially different epitopes stimulating different Helper T cell populations.
Nicola Borthwick, Sandra Silva-Arrieta, Anuska Llano, Masafumi Takiguchi, Christian Brander, and Tomáš Hanke. Novel Nested Peptide Epitopes Recognized by CD4+ T Cells Induced by HIV-1 Conserved-Region Vaccines. Vaccines, 8(1), 16 Jan 2020. PubMed ID: 31963212.
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