PMID- 35366796 OWN - NLM STAT- MEDLINE DCOM- 20220405 LR - 20230208 IS - 1471-2172 (Electronic) IS - 1471-2172 (Linking) VI - 23 IP - 1 DP - 2022 Apr 2 TI - A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design. PG - 15 LID - 10.1186/s12865-022-00491-7 [doi] LID - 15 AB - BACKGROUND: Identifying immunogens which can elicit effective T cell responses against human immunodeficiency virus type 1 (HIV-1) is important for developing a T-cell based vaccine. It has been reported that human leukocyte antigen (HLA)-B*13-restricted T-cell responses contributed to HIV control in subtype B' and C infected individuals. However, the kinetics of B*13-restricted T-cell responses, viral evolution within epitopes, and the impact on disease progression in CRF01_AE subtype HIV-1-infected men who have sex with men (MSM) are not known. RESULTS: Interferon-gamma ELISPOT assays and deep sequencing of viral RNAs were done in 14 early HLA-B*13-positive CRF01_AE subtype HIV-1-infected MSM. We found that responses to RQEILDLWV (Nef(106-114), RV9), GQMREPRGSDI (Gag(226-236), GI11), GQDQWTYQI (Pol(487-498), GI9), and VQNAQGQMV (Gag(135-143), VV9) were dominant. A higher relative magnitude of Gag-specific T-cell responses, contributed to viral control, whereas Nef-specific T-cell responses were associated with rapid disease progression. GI11 (Gag) was conserved and strong GI11 (Gag)-specific T-cell responses showed cross-reactivity with a dominant variant, M228I, found in 3/12 patients; GI11 (Gag)-specific T-cell responses were positively associated with CD4 T-cell counts (R = 0.716, P = 0.046). Interestingly, the GI9 (Pol) epitope was also conserved, but GI9 (Pol)-specific T-cell responses did not influence disease progression (P > 0.05), while a D490G variant identified in one patient did not affect CD4 T-cell counts. All the other epitopes studied [VV9 (Gag), RQYDQILIEI (Pol(113-122), RI10), HQSLSPRTL (Gag(144-152), HL9), and RQANFLGRL (Gag(429-437,) RL9)] developed escape mutations within 1 year of infection, which may have contributed to overall disease progression. Intriguingly, we found early RV9 (Nef)-specific T-cell responses were associated with rapid disease progression, likely due to escape mutations. CONCLUSIONS: Our study strongly suggested the inclusion of GI11 (Gag) and exclusion of RV9 (Nef) for T-cell-based vaccine design for B*13-positive CRF01_AE subtype HIV-1-infected MSM and high-risk individuals. CI - (c) 2022. The Author(s). FAU - Zhang, Hui AU - Zhang H AD - NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. AD - Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China. AD - Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou, 310003, China. FAU - He, Chuan AU - He C AD - NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. AD - Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China. AD - Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou, 310003, China. AD - Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. FAU - Jiang, Fanming AU - Jiang F AD - NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. AD - Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China. AD - Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou, 310003, China. AD - Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. FAU - Cao, Shuang AU - Cao S AD - NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. AD - Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China. AD - Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou, 310003, China. AD - Department of Laboratory Medicine, China Medical University Shengjing Hospital Nanhu Branch, Shenyang, 110001, China. FAU - Zhao, Bin AU - Zhao B AD - NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. AD - Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China. AD - Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou, 310003, China. FAU - Ding, Haibo AU - Ding H AD - NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. AD - Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China. AD - Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou, 310003, China. FAU - Dong, Tao AU - Dong T AD - Nuffield Department of Medicine, Chinese Academy of Medical Sciences Oxford Institute, Oxford University, Oxford, UK. AD - Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford, UK. FAU - Han, Xiaoxu AU - Han X AD - NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. xxhan@yeah.net. AD - Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China. xxhan@yeah.net. AD - Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. xxhan@yeah.net. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou, 310003, China. xxhan@yeah.net. FAU - Shang, Hong AU - Shang H AD - NHC Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China. hongshang100@hotmail.com. AD - Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China. hongshang100@hotmail.com. AD - Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. hongshang100@hotmail.com. AD - Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Street, Hangzhou, 310003, China. hongshang100@hotmail.com. LA - eng GR - MR/L018942/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20220402 PL - England TA - BMC Immunol JT - BMC immunology JID - 100966980 RN - 0 (HLA-B Antigens) SB - IM MH - *HIV Infections MH - *HIV-1/physiology MH - HLA-B Antigens MH - Homosexuality, Male MH - Humans MH - Male MH - *Sexual and Gender Minorities MH - T-Lymphocytes PMC - PMC8976269 OTO - NOTNLM OT - CRF01_AE OT - Epitope OT - Escape mutation OT - HIV-1 OT - HLA-B*13 OT - T-cell response COIS- The authors declare that they have no competing interests. EDAT- 2022/04/04 06:00 MHDA- 2022/04/06 06:00 PMCR- 2022/04/02 CRDT- 2022/04/03 20:21 PHST- 2021/02/09 00:00 [received] PHST- 2022/03/24 00:00 [accepted] PHST- 2022/04/03 20:21 [entrez] PHST- 2022/04/04 06:00 [pubmed] PHST- 2022/04/06 06:00 [medline] PHST- 2022/04/02 00:00 [pmc-release] AID - 10.1186/s12865-022-00491-7 [pii] AID - 491 [pii] AID - 10.1186/s12865-022-00491-7 [doi] PST - epublish SO - BMC Immunol. 2022 Apr 2;23(1):15. doi: 10.1186/s12865-022-00491-7.