Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Alrubayyi, Aljawharah; Gea‐Mallorquí, Ester; Touizer, Emma; Hameiri-Bowen, Dan; Kopycinski, Jakub; Charlton, Bethany; Fisher-Pearson, Natasha; Muir, Luke; Rosa, Annachiara; Roustan, Chloë; Earl, Christopher; Cherepanov, Peter; Pellegrino, Pierre; Waters, Laura; Burns, Fiona; Kinloch, S; Dong, Tao; Dorrell, Lucy; Rowland‐Jones, Sarah; McCoy, Laura E; Peppa, Dimitra

doi:10.21203/rs.3.rs-309746/v1

Cited by 10 publications

(9 citation statements)

References 71 publications

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“…Similar findings were reported for the mRNA-1273 COVID-19 vaccine, and found to be age-dependent, pointing to immune aging as a contributing factor (20, 21). This comprehensive analysis of humoral and cellular immunity is consistent with studies of COVID-19 in healthy adults and PWH showing durable immune responses up to 7 months post infection (19, 52, 56, 57). Further follow up at 12 months and beyond will be important to determine the longer-term persistence of responses, especially when considering the value of booster doses.…”

Section: Discussionsupporting

confidence: 87%

Durability of ChAdOx1 nCov-19 (AZD1222) vaccination in people living with HIV - responses to SARS-CoV-2, variants of concern and circulating coronaviruses

Ogbe

Pace

Bittaye

et al. 2021

Preprint

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Duration of protection from SARS-CoV-2 infection in people with HIV (PWH) following vaccination is unclear. In a sub-study of the phase 2/3 the COV002 trial (NCT04400838), 54 HIV positive male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells >350 cells/ul) received two doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and MesoScale Discovery (MSD)), neutralisation, ACE-2 inhibition, gamma interferon ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that 6 months after vaccination the majority of measurable immune responses were greater than pre-vaccination baseline, but with evidence of a decline in both humoral and cell mediated immunity. There was, however, no significant difference compared to a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although were lower than wild type. Pre-existing cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater post-vaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the on-going policy to vaccinate PWH against SARS-CoV-2, and underpin the need for long-term monitoring of responses after vaccination.

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Section: Discussionsupporting

confidence: 87%

Durability of ChAdOx1 nCov-19 (AZD1222) vaccination in people living with HIV - responses to SARS-CoV-2, variants of concern and circulating coronaviruses

Ogbe

Pace

Bittaye

et al. 2021

Preprint

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“…Cellular immune responses against SARS-CoV-2 are diminished in PWH Advancing on our studies, we aimed to determine T cell responses against SARS-CoV-2 antigens and peptide pools, as it was described elsewhere (9,15). Hence, PBMCs from each donor were stimulated in the presence of proteins or peptide pools encompassing both Spike and Nucleocapside proteins and afterwards the IFN-γ-producing cells were determined by ELISpot.…”

Section: Pwh Display a Distinctive Immune Pro Le Of Peripheral Leucocytes' Populationsmentioning

confidence: 99%

“…Studies on humoral immune responses against SARS-CoV-2 in HIV-immunosuppressed individuals are scarce and controversial. On one hand, it has been described that antibodies against SARS-CoV-2 are detected in people with HIV (PWH) with previous history of COVID-19, although with lower conversion rates when compared to HIV-naïve persons (8,9). On the other hand, it was shown that similar antibody responses can be achieved by PWH on ART with complete HIV suppression compared to HIV-uninfected individuals (10).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, it was shown that similar antibody responses can be achieved by PWH on ART with complete HIV suppression compared to HIV-uninfected individuals (10). In addition, memory cellular immunity could be assessed after SARS-CoV-2 infection in some cohorts of PWH (9). A deeper understanding about this issue is fundamental to applying an optimal vaccination strategy to this population.…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 Humoral and Cellular Immune Responses in COVID-19 Convalescent Individuals With HIV

Giannone

Vecchione

Czernikier

et al. 2022

Preprint

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Background SARS-CoV-2-specific immune response features in people with HIV infection (PWH) remain to be fully elucidated. We aimed to evaluate the impact of HIV over humoral and cellular responses in COVID-19 convalescent PWH. Methods Blood samples from 29 PWH with preserved CD4+T-cell counts on ART and 29 HIV-negative (HIVneg) donors were included. SARS-CoV-2-specific IgG levels and IgG titers were determined by ELISA. Antibody neutralization capacity was evaluated against the reference B1 strain SARS-CoV-2. IFN-γ-secreting cells were detected by ELISpot using SARS-CoV-2 Spike, RBD, or Nucleocapsid protein or overlapping peptide pools. Frequency and phenotype of T, B and NK cells and levels of soluble cytokines and chemokines were assessed by flow cytometry. Results SARS-CoV-2-specific antibodies were detected on 65.5% of PWH and 79.3% of HIVneg individuals, with no differences in serum IgG levels and anti-SARS-CoV-2 neutralizing antibodies. All donors exhibited SARS-CoV-2-specific cellular immunity, including those with undetectable antibody responses. PWH showed diminished percentages of antibody-secreting cells compared to HIVneg cohort, with similar B cell proportions between groups. PWH presented an increment in T follicular helper (Tfh, CD4+CXCR5+) percentage, which negatively correlated with IgG titers. Additionally, CD4+PD1+ and CD8+HLA-DR+ cell frequencies were augmented in PWH. Moreover, PWH presented a high proportion of CD95+, CD25+, NKp46+, HLA-DR+, and CD38+/HLA-DR+ NK cells. Both groups displayed similar Tregs frequency, effector/memory, and T-helper profile for CD4TL, exhaustion and memory phenotypes for CD8TL and subtle differences in classical monocytes. Profile of circulating cytokines and chemokines was significantly different between both groups. Magnitude of IFN-γ responses to S or N proteins, and RBD was lower in PWH compared to HIVneg donors. Correlation analysis of immune and clinical parameters showed a distinct immune landscape in the PWH group. Conclusions PWH showed a distinctive immune profile although severity of COVID-19 was not exacerbated. PWH with conserved CD4+T-cell counts exerted both humoral and cellular responses against SARS-CoV-2. Even though cellular response was lower compared to HIVneg individuals, PWH achieved similar antibody responses with a high neutralization capacity. These data reinforce the impact of ART, not only in controlling HIV but also other infections.

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“…Another study including 22 studies and 20,982,498 participants revealed that PLWH had a significantly higher risk of SARS-CoV-2 infection than HIV-negative individuals [5]. These multi-morbidities are driven by residual inflammation on ART and ongoing immune dysregulation [6] that could influence COVID-19 disease severity, the durability of protective antiviral responses, and responsiveness to vaccination [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Systematic review and meta-analysis of COVID-19 vaccines safety, tolerability, and efficacy among HIV-infected patients

Tamuzi

Muyaya

Mitra

et al. 2022

Preprint

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Objective To conduct a comprehensive systematic review and meta-analysis of all recommended SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) vaccines in people living with HIV (PLWH), as well as an overview of the safety, tolerability, and efficacy of the vaccines in PLWH. Methods We searched six databases, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Medline, Medrxiv, Global research on COVID-19 database, and Google Scholar for studies investigating the effects of SARS-CoV-2 vaccines on PLWH. Results of the association were summarised by SARS-CoV-2 IgG seroconversion and level, vaccines efficacy and tolerability. A meta-analysis was performed for studies, using random-effects model and a pooled RR with 95% CI was reported. Results Twenty-three of the 1052 studies screened met the inclusion criteria. The review included 28, 246 participants among whom 79.55% (22,469/28, 246) were PLWH with median CD4 >=200 cells/mm3. The pooled estimate of SARS-CoV-2 IgG seroconversion and positive neutralizing antibodies after the second vaccination dose between PLWH vs HIV negative were RR 0.95 (95%CI: 0.92 to 0.99, P = 0.006) and 0.88 (95%CI: 0.82 to 0.95, P = 0.0007), respectively. The mean difference of IgG antibodies level (BAU/ml) was found higher in mRNA vaccines MD -1444.97 (95%CI: -1871.39 to -1018.55). PLWH with CD4 less than 500 cells/mm3 had 15% risk reduction of neutralizing antibodies response compared to those with CD4>=500 cells/mm3 (P = 0.003). The SARS-CoV-2 vaccine effectiveness was 65% (95%CI: 56% to 72%, P <0.001) among vaccinated compared to unvaccinated PLWH. PLWH with CD4 count <350 cells/mm3 had lower vaccine effectiveness compared to CD4 count >=350 cells/mm3 with 59% vs 72%, respectively. Vaccine tolerability was the same between PLWH and HIV negatives. Conclusion According to our findings, PLWH with CD4>=200 cells/mm3 had lower immunogenicity and antigenicity in COVID-19 vaccines than HIV negatives. Additional doses of SARS-CoV-2 vaccination are needful in PLWH.

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Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Cited by 10 publications

References 71 publications

Durability of ChAdOx1 nCov-19 (AZD1222) vaccination in people living with HIV - responses to SARS-CoV-2, variants of concern and circulating coronaviruses

Durability of ChAdOx1 nCov-19 (AZD1222) vaccination in people living with HIV - responses to SARS-CoV-2, variants of concern and circulating coronaviruses

SARS-CoV-2 Humoral and Cellular Immune Responses in COVID-19 Convalescent Individuals With HIV

Systematic review and meta-analysis of COVID-19 vaccines safety, tolerability, and efficacy among HIV-infected patients

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