Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV
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Abstract
Despite the development of vaccines, which protect healthy people from severe and life-threatening Covid-19, the immunological responses of people with secondary immunodeficiencies to these vaccines remain incompletely understood. Here, we investigated the humoral and cellular immune responses elicited by mRNA-based SARS-CoV-2 vaccines in a cohort of people living with HIV (PLWH) receiving anti-retroviral therapy. While antibody responses in PLWH increased progressively after each vaccination, they were significantly reduced compared to the HIV-negative control group. This was particularly noteworthy for the Delta and Omicron variants. In contrast, CD4+ Th cell responses exhibited a vaccination-dependent increase, which was comparable in both groups. Interestingly, CD4+ T cell activation negatively correlated with the CD4 to CD8 ratio, indicating that low CD4+ T cell numbers do not necessarily interfere with cellular immune responses. Our data demonstrate that despite the lower CD4+ T cell counts SARS-CoV-2 vaccination results in potent cellular immune responses in PLWH. However, the reduced humoral response also provides strong evidence to consider PLWH as vulnerable group and suggests subsequent vaccinations being required to enhance their protection against COVID-19.
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SciScore for 10.1101/2022.04.08.22273605: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study design: The study was authorized by the local ethics committee of the Ruhr-University Bochum (21-7351 and 20-6953-bio).
Consent: The written informed consent was obtained from all the patients.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Anti-SARS-CoV-2 spike antibody titer: Plasma samples were analyzed for the spike (receptor-binding domain [RBD]; sequence derived from the original wildtype SARS-CoV-2 strain) specific immunoglobulin G antibodies by enzyme-linked immunosorbent assay (ELISA) as described previously 38. Anti-SARS-CoV…SciScore for 10.1101/2022.04.08.22273605: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study design: The study was authorized by the local ethics committee of the Ruhr-University Bochum (21-7351 and 20-6953-bio).
Consent: The written informed consent was obtained from all the patients.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Anti-SARS-CoV-2 spike antibody titer: Plasma samples were analyzed for the spike (receptor-binding domain [RBD]; sequence derived from the original wildtype SARS-CoV-2 strain) specific immunoglobulin G antibodies by enzyme-linked immunosorbent assay (ELISA) as described previously 38. Anti-SARS-CoV-2suggested: NoneExperimental Models: Cell Lines Sentences Resources Single cycle VSV*ΔG(FLuc) pseudoviruses bearing the SARS-CoV-2 spike (D614G) protein 40 or SARS-CoV-2 B.1.617.2 (Delta) (EPI_ISL_1921353) spike in the envelope were incubated with quadruplicates of two-fold serial dilutions from 1:20 to 1:2560 of immune sera in 96-well plates prior to infection of Vero E6 cells (1×104 cells/well) in DMEM with 10% FBS (Life Technologies). Vero E6suggested: NoneSoftware and Algorithms Sentences Resources PBMC stimulation using SARS-CoV-2 peptide pool: PBMCs were thawed in a 37 °C water bath and diluted in 10 ml RPMI 1640 with Glutamine (Capricorn) with 5 % human AB serum (PAN-Biotech) and 5 U/ml Benzonase (Merck/Sigma) and centrifuged at 400 g for 5 min. Merck/Sigmasuggested: NoneStatistics: Mann-Whitney or Kruskal–Wallis one-way ANOVA tests were performed to calculate statistical significance using Prism (GraphPad Software v9.2.0, San Diego, CA). Prismsuggested: (PRISM, RRID:SCR_005375)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of the study: The PLWH participants in our study received well-adjusted anti-retroviral therapy (ART) and had CD4+ T cells counts higher than 200 cells/μl. Whether immune responses upon COVID-19 vaccination correlate with T cell numbers in the peripheral blood awaits the analysis of a larger cohort with more diverse T cell counts. Moreover, we did not test directly for vaccine safety or efficacy since this would be beyond the scope of this study. Nevertheless, no gross adverse effects were reported by the participants of our PLWH cohort. Furthermore, our results suggest that vaccination of PLWH with COVID-19 mRNA vaccines might elicit partial humoral and cellular immune protection. Future studies have to show, whether or not booster vaccination will enhance immune protection, especially against upcoming variants of concern.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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