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.

Abstract

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-γ 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 (Nef106-114, RV9), GQMREPRGSDI (Gag226-236, GI11), GQDQWTYQI (Pol487-498, GI9), and VQNAQGQMV (Gag135-143, 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 (Pol113-122, RI10), HQSLSPRTL (Gag144-152, HL9), and RQANFLGRL (Gag429-437, 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.

• Authors: Hui Zhang, Chuan He, Fanming Jiang, Shuang Cao, Bin Zhao, Haibo Ding, Tao Dong, Xiaoxu Han, Hong Shang
• Journal: BMC immunology (BMC Immunol) Vol. 23 Issue 1 Pg. 15 (04 02 2022) ISSN: 1471-2172 [Electronic] England
• PMID: 35366796 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• HLA-B Antigens

Topics

• HIV Infections
• HIV-1 (physiology)
• HLA-B Antigens
• Homosexuality, Male
• Humans
• Male
• Sexual and Gender Minorities
• T-Lymphocytes