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Gag Epitope Map
||VID418: A*02:01, A*24:02, B*07:02, B*27:05, C*01:02, C*07:02, DQB1*03:01, DQB1*03:03, DRB1*04:01, 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 418 had a stimulatory response to EVIPMFTALSEGAT (ET14/HC003B), as well as related 15-mer EVIPMFTALSEGATP and shorter peptides, EVIPMFTALSEGA (EA13/HC003D), EVIPMFTALSEG (EG12/HC003F), EVIPMFTALSE (EE11/HC003H), and EVIPMFTALS (ES10/HC003J). In addition to IFN-γ, TNF-α was also produced.
- Epitope Location Finder tool predicts epitope cores at EVIPMFTALS and FTALSEGAT for DRB1*0401 and VIPMPT and LSEGAT for DRB1*0701, both of which are predicted HLA.
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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