Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy

  1. Zabrina L. Brumme
  2. Francis Mwimanzi
  3. Hope R. Lapointe
  4. Peter K. Cheung
  5. Yurou Sang
  6. Maggie C. Duncan
  7. Fatima Yaseen
  8. Olga Agafitei
  9. Siobhan Ennis
  10. Kurtis Ng
  11. Simran Basra
  12. Li Yi Lim
  13. Rebecca Kalikawe
  14. Sarah Speckmaier
  15. Nadia Moran-Garcia
  16. Landon Young
  17. Hesham Ali
  18. Bruce Ganase
  19. Gisele Umviligihozo
  20. F. Harrison Omondi
  21. Kieran Atkinson
  22. Hanwei Sudderuddin
  23. Junine Toy
  24. Paul Sereda
  25. Laura Burns
  26. Cecilia T. Costiniuk
  27. Curtis Cooper
  28. Aslam H. Anis
  29. Victor Leung
  30. Daniel Holmes
  31. Mari L. DeMarco
  32. Janet Simons
  33. Malcolm Hedgcock
  34. Marc G. Romney
  35. Rolando Barrios
  36. Silvia Guillemi
  37. Chanson J. Brumme
  38. Ralph Pantophlet
  39. Julio S. G. Montaner
  40. Masahiro Niikura
  41. Marianne Harris
  42. Mark Hull
  43. Mark A. Brockman

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Abstract

Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525–935) cells/mm 3 , though nadir CD4+ T-cell counts ranged as low as <10 cells/mm 3 . After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability.

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  1. Version published to 10.1038/s41541-022-00452-6
  2. Version published to 10.1101/2021.10.03.21264320v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.10.03.21264320: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Specimens were processed on the day of collection and frozen until analysis.
    Consent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Binding antibody assays: We measured total binding antibodies against SARS-CoV-2 nucleocapsid (N) and spike receptor binding domain (RBD) in serum using the Roche Elecsys Anti-SARS-CoV-2 and Elecsys Anti-SARS-CoV-2 S assays, respectively.
    SARS-CoV-2 nucleocapsid (N) and spike receptor binding domain (RBD
    suggested: None
    ACE2 displacement assay: We assessed the ability of plasma antibodies to block the interaction between RBD and the ACE2 receptor using the V-plex SARS-CoV-2 Panel 11 (ACE2) kit on a MESO QuickPlex SQ120 instrument (Meso Scale Discovery) at the manufacturer’s recommended 1:20 dilution.
    ACE2
    suggested: None
    Software and Algorithms
    SentencesResources
    Clinical information for PLWH was recovered from the BC Centre for Excellence in HIV/AIDS Drug Treatment Program Database, which houses clinical records for all PLWH receiving care in BC.
    HIV/AIDS Drug Treatment Program
    suggested: (National Center for Research Resources - Primate Resources, RRID:SCR_006863)
    Analyses were conducted using Prism v9.2.0 (GraphPad).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (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:
    Our study has several limitations. Our results may not be generalizable to individuals with untreated HIV and/or who have CD4+ T-cell counts <200 cells/mm3. Our study did not include children or adolescents living with HIV. As the precise immune correlates of protection for SARS-CoV-2 transmission and disease severity remain incompletely characterized [56], the implications of our results on individual-level protection from SARS-CoV-2 infection and COVID-19 remain uncertain. The relationship between vaccine-induced antibody concentrations in blood and at mucosal sites, which may be a better correlate of protection, is also incompletely understood, though a recent study identified anti-RBD IgG antibodies in saliva in 100% of participants following a two-dose COVID-19 vaccine series [57]. We did not investigate vaccine-induced T-cell responses, though two recent studies have demonstrated comparable anti-spike T-cell responses in PLWH compared to controls [10, 34]. Due to power considerations, we did not investigate potential differences in immune responses between the two mRNA vaccines [58, 59]. The latest time-point we analyzed was one month after the second vaccine dose, so analyses of COVID-19 vaccine durability are also needed. Taken together with existing data [10, 33-35], our results indicate that, one month after having received two COVID-19 vaccine doses, adults with HIV on suppressive antiretroviral therapy with CD4+ T-cell counts in the healthy range mount broadly com...

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.10.03.21264320v1 on medRxiv