People With Human Immunodeficiency Virus Receiving Suppressive Antiretroviral Therapy Show Typical Antibody Durability After Dual Coronavirus Disease 2019 Vaccination and Strong Third Dose Responses
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Abstract
Background
Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) (PLWH), as do initial responses to a third dose.
Methods
We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls.
Results
Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post–third-dose humoral responses substantially exceeded post–second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post–third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post–third-dose responses.
Conclusion
PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.
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SciScore for 10.1101/2022.03.22.22272793: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Ethics approval: All participants provided written informed consent. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Binding antibody assays: We measured total binding antibodies against SARS-CoV-2 nucleocapsid (N) and spike (S) receptor binding domain (RBD) in serum using the Elecsys Anti-SARS-CoV-2 and Anti-SARS-CoV-2 S assays, respectively, on a Cobas e601 module analyzer (Roche Diagnostics). SARS-CoV-2 nucleocapsid ( N ) and spike ( S ) receptor binding domain ( RBDsuggested: NoneAnti-SARS-CoV-2suggested: NoneSoftware and Algorithms Sentences Resources Analyses were … SciScore for 10.1101/2022.03.22.22272793: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Ethics approval: All participants provided written informed consent. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Binding antibody assays: We measured total binding antibodies against SARS-CoV-2 nucleocapsid (N) and spike (S) receptor binding domain (RBD) in serum using the Elecsys Anti-SARS-CoV-2 and Anti-SARS-CoV-2 S assays, respectively, on a Cobas e601 module analyzer (Roche Diagnostics). SARS-CoV-2 nucleocapsid ( N ) and spike ( S ) receptor binding domain ( RBDsuggested: NoneAnti-SARS-CoV-2suggested: NoneSoftware and Algorithms Sentences Resources Analyses were conducted using Prism v9.2.0 (GraphPad). 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:Our study has several limitations. Our results may not be generalizable to PLWH who are not receiving antiretroviral therapy, who have multiple co-morbidities or who have CD4+ T-cell counts <200 cells/mm3. We found no evidence that a low nadir CD4+ T-cell count negatively influenced COVID-19 vaccine response however, indicating that prior low CD4 T+ cell counts will not necessarily compromise immune responses to COVID-19 vaccines presently. We did not investigate T-cell responses, which may play critical protective roles, particularly against variants [48, 49]. Individuals ≥70 years old and PLWH meeting priority criteria were eligible for full mRNA-1273 third doses, but we could not directly assess mRNA-1273 dose-related effects on immune responses due to incomplete dosing information. Finally, while immune correlates of vaccine-mediated protection are being elucidated for SARS-CoV-2 [50], the implications of our results on individual-level protection from infection and disease remain uncertain, particularly in the context of Omicron. In conclusion, adult PLWH with well-controlled viral loads and preserved CD4+ T-cell counts mount strong and functional antibody responses to two and three COVID-19 vaccine doses, including to Omicron, though it will be important to monitor these responses over time. Studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are also needed.
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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