Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Ad26.CoV2.S Vaccination in People Living With Human Immunodeficiency Virus (HIV)
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Abstract
Background
People living with HIV (PLWH) have been reported to have a higher risk of more severe COVID-19 disease and death. We assessed the ability of the Ad26.CoV2.S vaccine to elicit neutralizing activity against the Delta variant in PLWH relative to HIV-negative individuals. We also examined effects of HIV status and suppression on Delta neutralization response in SARS-CoV-2—infected unvaccinated participants.
Methods
We enrolled participants who were vaccinated through the SISONKE South African clinical trial of the Ad26.CoV2.S vaccine in healthcare workers (HCWs). PLWH in this group had well-controlled HIV infection. We also enrolled unvaccinated participants previously infected with SARS-CoV-2. Neutralization capacity was assessed by a live virus neutralization assay of the Delta variant.
Results
Most Ad26.CoV2.S vaccinated HCWs were previously infected with SARS-CoV-2. In this group, Delta variant neutralization was 9-fold higher compared with the infected-only group and 26-fold higher relative to the vaccinated-only group. No decrease in Delta variant neutralization was observed in PLWH relative to HIV-negative participants. In contrast, SARS-CoV-2—infected, unvaccinated PLWH showed 7-fold lower neutralization and a higher frequency of nonresponders, with the highest frequency of nonresponders in people with HIV viremia. Vaccinated-only participants showed low neutralization capacity.
Conclusions
The neutralization response of the Delta variant following Ad26.CoV2.S vaccination in PLWH with well-controlled HIV was not inferior to HIV-negative participants, irrespective of past SARS-CoV-2 infection. In SARS-CoV-2—infected and nonvaccinated participants, HIV infection reduced the neutralization response to SARS-CoV-2, with the strongest reduction in HIV viremic individuals.
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SciScore for 10.1101/2021.10.08.21264519: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: These participants are enrolled in a prospective cohort study approved by the Biomedical Research Ethics Committee at the University of KwaZulu–Natal (reference BREC/00001275/2020). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Cell lines have not been authenticated.
Contamination: The cell lines have been tested for mycoplasma contamination and are mycoplasma negative.Table 2: Resources
Antibodies Sentences Resources For experiments, plasma was serially diluted and the the GenScript A02051 anti-spike monoclonal antibody was added as a positive control to one column of wells. anti-spikeSciScore for 10.1101/2021.10.08.21264519: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: These participants are enrolled in a prospective cohort study approved by the Biomedical Research Ethics Committee at the University of KwaZulu–Natal (reference BREC/00001275/2020). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Cell lines have not been authenticated.
Contamination: The cell lines have been tested for mycoplasma contamination and are mycoplasma negative.Table 2: Resources
Antibodies Sentences Resources For experiments, plasma was serially diluted and the the GenScript A02051 anti-spike monoclonal antibody was added as a positive control to one column of wells. anti-spikesuggested: NoneSecondary goat anti-rabbit horseradish peroxidase (Abcam ab205718) antibody was added at 1 μg/mL and incubated for 2 h at room temperature with shaking. anti-rabbitsuggested: (Abcam Cat# ab205718, RRID:AB_2819160)Multi-epitope protein microarray: ImmuSAFE COVID-19 Array slides (Sengenics Corporation, Singapore) were used to measure the anti-SARS CoV-2 IgG and IgA antibodies against N and S proteins. anti-SARS CoV-2 IgGsuggested: NoneArrays were then incubated simultaneously with two detection antibodies: AF647 anti-human IgG and AF555 anti-human IgA (ThermoFisher; 1.25µg/ml each in 3ml assay buffer) for 30 min at RT with gentle agitation and dried by centrifugation at 1200× g for 2 min. anti-human IgGsuggested: Noneanti-human IgAsuggested: NoneExperimental Models: Cell Lines Sentences Resources H1299 cells were passaged every second day. H1299suggested: NCI-DTP Cat# NCI-H1299, RRID:CVCL_0060)ACE2-expressing H1299-E3 cells were seeded at 1.5 × 105 cells per mL and incubated for 18–20 h. H1299-E3suggested: NoneThe viral supernatant (P2 stock) was aliquoted and stored at −80 °C and further passaged in Vero E6 cells to obtain the P3 stock used in experiments as follows: a T25 flask (Corning) was seeded with Vero E6 cells at 2 × 105 cells per mL and incubated for 18–20 h. Vero E6suggested: NoneSoftware and Algorithms Sentences Resources For microscopy images, automated image analysis was performed using a custom script in MATLAB v. MATLABsuggested: (MATLAB, RRID:SCR_001622)Arrays were then incubated simultaneously with two detection antibodies: AF647 anti-human IgG and AF555 anti-human IgA (ThermoFisher; 1.25µg/ml each in 3ml assay buffer) for 30 min at RT with gentle agitation and dried by centrifugation at 1200× g for 2 min. ThermoFishersuggested: (ThermoFisher; SL 8; Centrifuge, RRID:SCR_020809)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.
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