Despite delayed kinetics, people living with HIV achieve equivalent antibody function after SARS-CoV-2 infection or vaccination

Motsoeneng, Boitumelo M.; Manamela, Nelia P; Kaldine, Haajira; Kgagudi, Prudence; Hermanus, Tandile; Ayres, Frances; Makhado, Zanele; Moyo-Gwete, Thandeka; Mescht, Mieke A. van der; Abdullah, Fareed; Boswell, Michael T; Ueckermann, Veronica; Rossouw, Theresa M.; Madhi, Shabir А.; Moore, Penny L.; Richardson, Simone I.

doi:10.3389/fimmu.2023.1231276

Cited by 6 publications

(4 citation statements)

References 71 publications

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“…Even viremic PLWH showed increased binding and neutralizing antibody responses after BNT162b2 vaccination, and these were within the range seen in the other participants. These results are consistent with previous studies that PLWH have good antibody responses to vaccination [ 19 , 38 , 39 , 62 ] with the exception of those with CD4+ T cell concentrations than 200 cells/mm 3 [ 34 , 36 , 37 , 63 , 64 ]. T-cell responses were more strongly affected by HIV status: they were significantly lower for spike-specific CD4+ T cells in PLWH boosted with a full-dose of BNT162b2.…”

Section: Discussionsupporting

confidence: 93%

“…PLWH, especially those with low CD4 T-cell counts, have moderately worse COVID-19 outcomes [27][28][29][30][31][32][33][34][35]. This is associated with lower and delayed neutralizing antibody titers in response to SARS-CoV-2 infection [19,34,36], more pronounced in PLWH with HIV viremia [19]. However, similar to results reported for the AstraZeneca ChAdOx and the Pfizer BNT162b2 vaccines [37][38][39][40][41], there was no observed difference between PLWH and HIV-negative individuals in neutralizing antibody titers against SARS-CoV-2 spike after Ad26.COV2.S vaccination [19,36].…”

Section: Introductionmentioning

confidence: 99%

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Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants

Riou,

Bhiman,

Ganga

et al. 2024

PLOS Glob Public Health

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We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Overall, in the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: The study has been registered to the South African National Clinical Trial Registry (SANCTR): DOH-27-012022-7841. The approval letter from SANCTR has been provided in the up-loaded documents.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants

Riou,

Bhiman,

Ganga

et al. 2024

PLOS Glob Public Health

Self Cite

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“…Even viremic PLWH showed increased binding and neutralizing antibody responses after BNT162b2 vaccination, and these were within the range seen in the other participants. These results are consistent with previous studies that PLWH have good antibody responses to vaccination [19,38,39,56] with the exception of those with CD4+ T cell concentrations than 200 cells/mm 3 [34,36,37,57,58]. T-cell responses were more strongly affected by HIV status: they were significantly lower for spike-specific CD4+ T cells in PLWH boosted with a full-dose of BNT162b2.…”

Section: Discussionsupporting

confidence: 91%

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants

Riou,

Bhiman,

Ganga

et al. 2023

Preprint

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BackgroundWe report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection.MethodsA total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated.ResultsNo vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting.ConclusionIn the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost.Trial RegistrationSouth African National Clinical Trial Registry (SANCR): DOH-27-012022-7841FundingSouth African Medical Research Council (SAMRC) and South African Department of Health (SA DoH).

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“…4, purple traces, and Extended Data Fig. 9), consistent with other recent studies of SARS-CoV-2 humoral immunity in PWH 8, 28 . Subsequently, in participants 16-036 and 15-030, serum binding to spike repeatedly exceeded the assay positivity threshold.…”

Section: Selection and Autologous Antibody Responsessupporting

confidence: 91%

Rapid Emergence and Evolution of SARS-CoV-2 Variants in Advanced HIV Infection

Ko,

Radecki,

Belinky

et al. 2024

Preprint

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Previous studies have linked the evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic variants to persistent infections in people with immunocompromising conditions1–4, but the evolutionary processes underlying these observations are incompletely understood. Here we used high-throughput, single-genome amplification and sequencing (HT-SGS) to obtain up to ∼103SARS-CoV-2 spike gene sequences in each of 184 respiratory samples from 22 people with HIV (PWH) and 25 people without HIV (PWOH). Twelve of 22 PWH had advanced HIV infection, defined by peripheral blood CD4 T cell counts (i.e., CD4 counts) <200 cells/μL. In PWOH and PWH with CD4 counts ≥200 cells/μL, most single-genome spike sequences in each person matched one haplotype that predominated throughout the infection. By contrast, people with advanced HIV showed elevated intra-host spike diversity with a median of 46 haplotypes per person (IQR 14-114). Higher intra-host spike diversity immediately after COVID-19 symptom onset predicted longer SARS-CoV-2 RNA shedding among PWH, and intra-host spike diversity at this timepoint was significantly higher in people with advanced HIV than in PWOH. Composition of spike sequence populations in people with advanced HIV fluctuated rapidly over time, with founder sequences often replaced by groups of new haplotypes. These population-level changes were associated with a high total burden of intra-host mutations and positive selection at functionally important residues. In several cases, delayed emergence of detectable serum binding to spike was associated with positive selection for presumptive antibody-escape mutations. Taken together, our findings show remarkable intra-host genetic diversity of SARS-CoV-2 in advanced HIV infection and suggest that adaptive intra-host SARS-CoV-2 evolution in this setting may contribute to the emergence of new variants of concern (VOCs).

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Despite delayed kinetics, people living with HIV achieve equivalent antibody function after SARS-CoV-2 infection or vaccination

Cited by 6 publications

References 71 publications

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants

Rapid Emergence and Evolution of SARS-CoV-2 Variants in Advanced HIV Infection

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