Editorial: HIV-Associated Immune Activation and Persistent Inflammation

Hoenigl, Martin; Kessler, Harald H.; Gianella, Sara

doi:10.3389/fimmu.2019.02858

Cited by 10 publications

(6 citation statements)

References 12 publications

(14 reference statements)

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“…This pattern has previously been observed in chronically inflamed patients, e.g. in patients infected with HIV ( 33 ). Though previous studies have reported higher level of circulating cytokines in patients with NSCLC ( 12 – 16 ), this paper is, to the best of our knowledge, the first to describe a complex immunoassay assessing the induced immune response ex vivo as a proxy for immune function in lung cancer patients.…”

Section: Discussionsupporting

confidence: 82%

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

et al. 2022

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IntroductionThe immune system has proven to be a key player in the progression as well as containment of cancer with new treatment strategies based on immunotherapy targeting this interaction. Assessing immune function could reveal critical information about the immune response to therapeutic interventions, revealing predictive biomarkers for tailored care and precision medicine.MethodsWe investigated immune function in 37 patients with inoperable non-small cell lung cancer (NSCLC) undergoing treatment with PD-L1 immune checkpoint inhibitor (ICI), chemotherapy (CT) or chemo-radiotherapy (CT/RT). Blood samples before (day 0) and during therapy (day 7, 21 and 80) were investigated by a standardized immunoassay, TruCulture®.ResultsOutcomes revealed a developing innate immune response induced by both immunotherapy and chemotherapy. NSCLC-patients displayed evidence of chronic innate immune activation and exhaustion prior to treatment. This pattern was particularly pronounced during treatment in patients dying within 12-months follow-up. Compared to treatment with CT, ICI demonstrated a higher ex vivo-stimulated release of proinflammatory cytokines.DiscussionThese preliminary findings may pave the way for tailored treatment and immune-monitoring.

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Section: Discussionsupporting

confidence: 82%

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

et al. 2022

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“…We observed IFN-γ production in both MOG and the medium with DMSO conditions in the PLWH group. This nonspecific spontaneous IFN-γ production by T cells from PLWH could be due to the higher chronic immune activation and persistent inflammation that has been reported before in PLWH [ 27 ]. That indeed immune activation leads to higher background spots in ELISpot assays was previously shown in HIV-negative individuals [ 28 ].…”

Section: Discussionmentioning

confidence: 86%

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Hensley¹,

Jongkees²,

GeurtsvanKessel³

et al. 2022

PLoS Med

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Background Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. Methods and findings We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44–60] years, 85.5% male) and 440 controls (median age 43 [IQR 33–53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/μL (IQR 520–913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322–1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508–0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250–500 cells/μL (2.845, 95% CI 1.876–4.314, p < 0.001) or >500 cells/μL (2.936, 95% CI 1.961–4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286–0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. Conclusions After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. Trial registration The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214.

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“…We observed a relevant IFN-γ production in the negative control stimulation in the PLWH group. Chronic immune activation and persistent inflammation has been reported before in chronic HIV patients, and could explain these results [27].…”

Section: Discussionmentioning

confidence: 73%

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV: a nationwide prospective cohort study in the Netherlands

Hensley

Jongkees

GeurtsvanKessel

et al. 2022

Preprint

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Background Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. Methods and Findings A prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines in adult PLWH, without prior COVID-19, compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response and reactogenicity. Between February-September 2021, 1154 PLWH (median age 53 [IQR 44-60], 86% male) and 440 controls (median age 43 [IQR 33-53], 29% male) were included. 884 PLWH received BNT162b2, 100 mRNA-1273, 150 ChAdOx1-S, and 20 Ad26.COV2.S. 99% were on antiretroviral therapy, 98% virally suppressed, and the median CD4+T-cell count was 710 cells/µL [IQR 520-913]. 247 controls received mRNA-1273, 94 BNT162b2, 26 ChAdOx1-S and 73 Ad26.COV2.S. After mRNA vaccination, geometric mean concentration was 1418 BAU/mL in PLWH (95%CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV-status remained associated with a decreased response (0.607, 95%CI 0.508-0.725). In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+T-cell counts 250-500 cells/µL (2.845, 95%CI 1.876-4.314) or >500 cells/µL (2.936, 95%CI 1.961-4.394), whilst a viral load >50 copies/mL was associated with a reduced response (0.454, 95%CI 0.286-0.720). Increased IFN-γ, CD4+, and CD8+T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation induced marker assays, comparable to controls. Reactogenicity was generally mild without vaccine-related SAE. Conclusion After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH. To reach and maintain the same serological responses and vaccine efficacy as HIV-negative controls, additional vaccinations are probably required.

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Editorial: HIV-Associated Immune Activation and Persistent Inflammation

Cited by 10 publications

References 12 publications

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV: a nationwide prospective cohort study in the Netherlands

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