||Li, Pingchao; Wang, Qian; He, Yizi; Yang, Chenchen; Zhang, Zhengyuan; Liu, Zijian; Liu, Bo; Yin, Li; Cui, Yilan; Hu, Peiyu; Liu, Yichu; Zheng, Pingqian; Wang, Wei; Qu, Linbing; Sun, Caijun; Guan, Suhua; Feng, Liqiang; Chen, Ling
|| Prolonged infection and possible evolution of SARS-CoV-2 in patients living with uncontrolled HIV-1 infection highlight the importance of an effective vaccination regimen, yet the immunogenicity of COVID-19 vaccines and predictive immune biomarkers have not been well investigated. Herein, we report that the magnitude and persistence of antibody and cell-mediated immunity (CMI) elicited by an Ad5-vectored COVID-19 vaccine are impaired in SIV-infected macaques with high viral loads (> 10(5) genome copies per ml plasma, SIVhi) but not in macaques with low viral loads (< 10(5), SIVlow). After a second vaccination, the immune responses are robustly enhanced in all uninfected and SIVlow macaques. These responses also show a moderate increase in 70% SIVhi macaques but decline sharply soon after. Further analysis reveals that decreased antibody and CMI responses are associated with reduced circulating follicular helper T cell (TFH) counts and aberrant CD4/CD8 ratios, respectively, indicating that dysregulation of CD4(+) T cells by SIV infection impairs the COVID-19 vaccine-induced immunity. Ad5-vectored COVID-19 vaccine shows no impact on SIV loads or SIV-specific CMI responses. Our study underscores the necessity of frequent booster vaccinations in HIV-infected patients and provides indicative biomarkers for predicting vaccination effectiveness in these patients.