Relatively preserved functional immune capacity with standard COVID-19 vaccine regimen in people living with HIV

Abstract

IntroductionPeople living with HIV (PLWH) are at a higher risk of severe disease with SARS-CoV-2 virus infection. COVID-19 vaccines are effective in most PLWH. However, suboptimal immune responses to the standard two-shot regimen are a concern, especially for those with moderate to severe immunodeficiency. An additional dose is recommended as part of the extended primary series in Taiwan. Herein, we study the efficacy of this additional shot in PLWH with mild immunodeficiency compared to that in healthy non-HIV people.MethodsIn total, 72 PLWH that were asymptomatic or with mild immunodeficiency (CD4 counts ≥200/mm3) and suppressed virology, and 362 healthcare workers of our hospital were enrolled. None of the participants had a history of SARS-CoV-2 infection. They received mRNA-1273 and ChAdOx1 vaccines. Anti-SARS-CoV-2 neutralizing and anti-Spike IgG antibodies, and SARS-CoV-2-specific T cell responses were evaluated.ResultsThe standard two-shot regimen elicited lower responses in PLWH than the healthcare workers without HIV infection, although the difference was statistically insignificant. They had comparable levels of neutralizing and anti-Spike antibodies and comparable effector CD4+ and CD8+ T cell responses. The third shot boosted the SARS-CoV-2 immunity significantly more with better antibody responses and higher IFN-γ and IL-2 responses of the CD4+ and CD8+ T cells in PLWH compared to those without HIV. Upon in vitro stimulation with extracted Wuhan strain SARS-CoV-2 proteins, CD8+ T cells from PLWH after 3 shots had more durable effector responses than the non-HIV controls with extended time of stimulation.ConclusionThis 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 third shot or natural infection.

T-Cell Responses to COVID-19 Vaccines and Breakthrough Infection in People Living with HIV Receiving Antiretroviral Therapy

“…Our results are broadly consistent with other recent studies showing that vaccineinduced spike-specific T-cell responses are equivalent in PLWH and controls without HIV, particularly among PLWH receiving antiretroviral therapy [16][17][18][19]24,25]. We found no association between CD4+ T-cell responses and neutralizing antibodies after two or three vaccine doses.…”

“…Studies analyzing vaccine-induced immune responses, including from our group, also confirm that PLWH, particularly those receiving suppressive antiretroviral therapy, mount robust humoral (antibody) responses to COVID-19 immunization [8][9][10][11][12][13][14][15]. However, comparably fewer studies have investigated the cellular immune response to COVID-19 vaccines in PLWH, which includes CD4+ helper T cells that play a central role in generating antigen-specific B cells and antibodies and CD8+ cytotoxic T cells that recognize and eliminate virus-infected cells [16][17][18][19]. Indeed, while COVID-19 vaccines typically induce potent T-cell responses in PLWH [18][19][20][21][22][23], the frequency of spike-specific CD4+ T cells following COVID-19 vaccination may be lower in PLWH, particularly among those with low CD4+ T-cell counts [24][25][26][27].…”

“…However, comparably fewer studies have investigated the cellular immune response to COVID-19 vaccines in PLWH, which includes CD4+ helper T cells that play a central role in generating antigen-specific B cells and antibodies and CD8+ cytotoxic T cells that recognize and eliminate virus-infected cells [16][17][18][19]. Indeed, while COVID-19 vaccines typically induce potent T-cell responses in PLWH [18][19][20][21][22][23], the frequency of spike-specific CD4+ T cells following COVID-19 vaccination may be lower in PLWH, particularly among those with low CD4+ T-cell counts [24][25][26][27]. A better understanding of T-cell responses elicited by COVID-19 vaccines and breakthrough SARS-CoV-2 infections will inform ongoing efforts to enhance protective immunity in PLWH.…”

Dynamics of T cell responses to COVID-19 vaccines and breakthrough infection in people living with HIV receiving antiretroviral therapy

“…Our results are broadly consistent with other recent studies showing that vaccineinduced spike-specific T cell responses are equivalent in PLWH and controls without HIV, particularly among PLWH receiving antiretroviral therapy [9,[17][18][19][20]23]. We found no association between CD4+ T cell responses and neutralizing antibodies after either two or three vaccine doses, suggesting that sufficient T cell help was provided to stimulate spike-specific B cell responses despite a wide range of antigen-specific CD4+ T cell frequencies induced by vaccination.…”

“…But comparably fewer studies have investigated the cellular immune response to COVID-19 vaccines in PLWH, which includes CD4+ helper T cells that play a central role in generating antigen-specific B cells and antibodies and CD8+ cytotoxic T cells that recognize and eliminate virus-infected cells [17][18][19][20]. Indeed, while COVID-19 vaccines typically induce strong T cell responses [21,22], the frequency of spike-specific CD4+ T cells following COVID-19 vaccination may be lower in PLWH, in particularly among those with low CD4+ T cell counts [9,23].…”