The humoral and cellular immune responses following booster vaccination with SARS-CoV-2 mRNA in people living with human immunodeficiency virus

Matsumoto, Yuji; Murata, Masayuki; Ohta, Azusa; Yamasaki, Sho; Ikezaki, Hiroaki; Toyoda, Kazuhiro; Shimono, Nobuyuki

doi:10.1016/j.jiac.2023.11.014

Cited by 2 publications

(4 citation statements)

References 14 publications

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“…Our results are broadly consistent with other recent studies showing that vaccine-induced spike-specific T cell responses are equivalent in PLWH and controls without HIV, particularly among PLWH receiving antiretroviral therapy [9, 17–20, 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.…”

Section: Discussionsupporting

confidence: 92%

“…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 [17–20]. 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]. A better understanding of T cell responses elicited by COVID-19 vaccines, as well as breakthrough SARS-CoV-2 infections, will inform ongoing efforts to enhance protective immunity in PLWH.…”

Section: Introductionmentioning

confidence: 99%

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

Datwani,

Kalikawe,

Waterworth

et al. 2024

Preprint

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Introduction: People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccination, but fewer studies have examined cellular immune responses to vaccination. We measured SARS-CoV-2 spike-specific CD4+ and CD8+ T cell responses generated by two and three doses of COVID-19 vaccine in PLWH receiving antiretroviral therapy, compared to control participants without HIV. We also quantified T cell responses after post-vaccine breakthrough infection, and receipt of fourth vaccine doses, in a subset of PLWH. Methods: We quantified CD4+ and CD8+ T cells reactive to overlapping peptides spanning the ancestral SARS-CoV-2 spike protein in 50 PLWH and 87 controls without HIV, using an activation induced marker (AIM) assay. All participants remained SARS-CoV-2 naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 controls post-third dose. Multivariable regression analyses were used to investigate relationships between sociodemographic, health and vaccine-related variables and vaccine-induced T cell responses, as well as breakthrough infection risk. Results: A third vaccine dose boosted spike-specific CD4+ and CD8+ T cell frequencies significantly above those measured after the second dose (all p<0.0001). Median T cell frequencies did not differ between PLWH and controls after the second dose (p>0.1), but CD8+ T cell responses were modestly lower in PLWH after the third dose (p=0.02), an observation that remained significant after adjustment for sociodemographic, health and vaccine-related variables (p=0.045). In PLWH who experienced breakthrough infection, median T cell frequencies increased even higher than those observed after three vaccine doses (p<0.03), and CD8+ T cell responses in this group remained higher even after a fourth vaccine dose (p=0.03). In multivariable analysis, the only factor associated with increased breakthrough infection risk was younger age, consistent with the rapid increases in SARS-CoV-2 seropositivity among younger adults in Canada after the initial appearance of the Omicron variant. Conclusion: PLWH receiving antiretroviral therapy mount strong T cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

Datwani,

Kalikawe,

Waterworth

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Discussionsupporting

confidence: 92%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Datwani,

Kalikawe,

Waterworth

et al. 2024

Viruses

View full text Add to dashboard Cite

People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccines, but fewer studies have examined cellular immune responses to the vaccinations. Here, we used an activation-induced marker (AIM) assay to quantify SARS-CoV-2 spike-specific CD4+ and CD8+ T cells generated by two and three doses of COVID-19 vaccines in 50 PLWH receiving antiretroviral therapy, compared to 87 control participants without HIV. In a subset of PLWH, T-cell responses were also assessed after post-vaccine breakthrough infections and/or receipt of a fourth vaccine dose. All participants remained SARS-CoV-2 infection-naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to a Nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 control participants after the third vaccine dose. Multivariable regression analyses were used to investigate the relationships between sociodemographic, health- and vaccine-related variables, vaccine-induced T-cell responses, and breakthrough infection risk. We observed that a third vaccine dose boosted spike-specific CD4+ and CD8+ T-cell frequencies significantly above those measured after the second dose (all p < 0.0001). Median T-cell frequencies did not differ between PLWH and controls after the second dose (p > 0.1), but CD8+ T-cell responses were modestly lower in PLWH after the third dose (p = 0.02), an observation that remained significant after adjusting for sociodemographic, health- and vaccine-related variables (p = 0.045). In PLWH who experienced a breakthrough infection, median T-cell frequencies increased even higher than those observed after three vaccine doses (p < 0.03), and CD8+ T-cell responses in this group remained higher even after a fourth vaccine dose (p = 0.03). In multivariable analyses, the only factor associated with an increased breakthrough infection risk was younger age, which is consistent with the rapid increase in SARS-CoV-2 seropositivity that was seen among younger adults in Canada after the initial appearance of the Omicron variant. These results indicate that PLWH receiving antiretroviral therapy mount strong T-cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection.

show abstract

The humoral and cellular immune responses following booster vaccination with SARS-CoV-2 mRNA in people living with human immunodeficiency virus

Cited by 2 publications

References 14 publications

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

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

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

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