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

  1. Kathryn S. Hensley
  2. Marlou J. Jongkees
  3. Daryl Geers
  4. Corine H. GeurtsvanKessel
  5. Yvonne M. Mueller
  6. Virgil A. S. H. Dalm
  7. Grigorios Papageorgiou
  8. Hanka Steggink
  9. Alicja Gorska
  10. Susanne Bogers
  11. Jan G. den Hollander
  12. Wouter F. W. Bierman
  13. Luc B. S. Gelinck
  14. Emile F. Schippers
  15. Heidi S. M. Ammerlaan
  16. Marc van der Valk
  17. Marit G. A. van Vonderen
  18. Corine E. Delsing
  19. Elisabeth H. Gisolf
  20. Anke H. W. Bruns
  21. Fanny N. Lauw
  22. Marvin A. H. Berrevoets
  23. Kim C. E. Sigaloff
  24. Robert Soetekouw
  25. Judith Branger
  26. Quirijn de Mast
  27. Adriana J. J. Lammers
  28. Selwyn H. Lowe
  29. Rory D. de Vries
  30. Peter D. Katsikis
  31. Bart J. A. Rijnders
  32. Kees Brinkman
  33. Anna H. E. Roukens
  34. Casper Rokx

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Abstract

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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  1. Version published to 10.1371/journal.pmed.1003979
  2. ScreenIT

    SciScore for 10.1101/2022.03.31.22273221: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Written informed consent was obtained from all participants.
    IRB: The trial was reviewed and approved by the Medical research Ethics Committees United Nieuwegein (MEC-U, reference 20.125).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisWe justified the sample size by calculating that 556 PLWH receiving mRNA vaccines would be sufficient to detect a serological response rate of 90% or lower compared to a hypothetical 95% response rate in controls with >80% power.

    Table 2: Resources

    Antibodies
    SentencesResources
    We defined a hyporesponse as 50-300 BAU/mL and non-response as <50 BAU/mL, based on previous studies which showed correlation of antibody concentration of 300 BAU/mL with a neutralising capacity of 1:40.[9, 22] In the subgroup, anti-spike SARS-CoV-2 specific T-cell response, and antibody response 21 days after the first vaccine dose were evaluated.
    anti-spike SARS-CoV-2 specific T-cell response,
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analysed using IBM SPSS Statistics 25, R (v. 4.1.2), and GraphPad Prism 8.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Flow cytometry data were analysed using FlowJo software version 10.8.1.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    About SciScore

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  3. Version published to 10.1101/2022.03.31.22273221v1 on medRxiv