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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 had a stimulatory response to GFRKYTAFTIP (HC079G), 15-mer PLDEGFRKYTAFTIP as well as shorter peptides, LDEGFRKYTAFTIP (HC079A), PLDEGFRKYTAFTI (HC079B), DEGFRKYTAFTIP (HC079C), PLDEGFRKYTAFT (HC079D), PLDEGFRKYTA (HC079H/HC078G/PA11), FRKYTAFTIP (FP10/HC079I), and PLDEGFRKY (PY9/HC079L). In addition to IFN-γ, TNF-α was also produced but not for HC079B/D/H and L.
- The minimum epitopes were FRKYTAFTIP (FP10/HC079I) and PLDEGFRKY (PY9/HC079L) with no known HLA binding prediction.
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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