Abstract

Abstract People living with HIV (PLWH) are at a higher risk of sever disease with SARS-CoV-2 virus infection. COVID-19 vaccines are effective in most PLWH, with significant reduction in the risk of severe disease or death when the standard 2-shot regimen is taken. However, suboptimal immune response to the standard course of vaccination is a concern for PLWH, especially for those with moderate to severe immunodeficiency. An additional dose is recommended as part of the extended primary series. In Taiwan, this additional dose is endorsed even for asymptomatic or mild immunodeficiency with CD4 counts >200/mm 3and suppressed virology. We aimed to investigate the immune responses with the additional dose in PLWH asymptomatic or with mild immunodeficiency. We collected peripheral blood mononuclear cells (PBMC) from 72 PLWH asymptomatic or with mild immunodeficiency and from 362 non-HIV subjects, after two and three shots respectively. Two shots elicited lower responses in PLWH, although the difference was statistically insignificant. They have comparable levels of neutralizing and anti-S antibodies and comparable effector CD4+ and CD8+ T cell responses. The 3 rdshot boosted the SARS-CoV-2 immunity significantly more in PLWH compared to the non-HIV people. Upon in vitro stimulation with extracted Wuhan strain SARS-CoV-2 proteins, CD8+ T cells from PLWH after 3 shots has more durable effector responses than the non-HIV controls with extended time of stimulation. This subtle difference between PLWH and non-HIV people implied immune exhaustion with two shots in non-HIV people. Slightly compromised immunity in PLWH indeed preserved the functional capacity for further response to the 3 rdshot or natural infection. The Research Center for Emerging Viral Infections receives support from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE), Taiwan and NSTC 111-2634-F-182-001 from the National Science and Technology Council, Taiwan. This work was supported by Projects CMRPG3M1811 (CTH) from the Medical Research Project Fund, Chang Gung Memorial Hospital, Taiwan.

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