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. 2024 Aug 16;79(2):364-374.
doi: 10.1093/cid/ciae192.

COVID-19 Vaccine Efficacy in Participants With Weakened Immune Systems From 4 Randomized Controlled Trials

Amy C Sherman  1 , Jessica Tuan  2 , Valeria D Cantos  3 , Oladunni Adeyiga  4 , Scott Mahoney  5 , Ana M Ortega-Villa  6 , Amy Tillman  7 , Jennifer Whitaker  8 , Amanda S Woodward Davis  9 , Brett Leav  10 , Ian Hirsch  11 , Jerald Sadoff  12 , Lisa M Dunkle  13 , Peter B Gilbert  9 , Holly E Janes  9 , James G Kublin  9 , Paul A Goepfert  14 , Karen Kotloff  15 , Nadine Rouphael  16 , Ann R Falsey  17 , Hana M El Sahly  8 , Magdalena E Sobieszczyk  18 , Yunda Huang  9 , Kathleen M Neuzil  19 , Lawrence Corey  9   20 , Beatriz Grinsztejn  21 , Glenda Gray  22   23 , Martha Nason  6 , Lindsey R Baden  1 , Cynthia L Gay  24
Affiliations

COVID-19 Vaccine Efficacy in Participants With Weakened Immune Systems From 4 Randomized Controlled Trials

Amy C Sherman et al. Clin Infect Dis. .

Abstract

Background: Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions.

Methods: A post hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, coronavirus disease 2019 (COVID-19) vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS individuals starting at 14 days after completion of the primary series through the blinded phase for each of the 4 trials. An analysis of participants living with well-controlled human immunodeficiency virus was conducted using the same methods.

Results: A total of 3852/30 351 (12.7%) Moderna participants, 3088/29 868 (10.3%) Novavax participants, 3549/32 380 (11.0%) AstraZeneca participants, and 5047/43 788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (vs placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants versus non-TIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with human immunodeficiency virus.

Conclusions: For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared with those with non-TIS in the 4 COVID-19 vaccine randomized controlled efficacy trials.

Keywords: COVID-19; HIV; immunocompromised; vaccine; vaccine efficacy.

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Conflict of interest statement

Potential conflicts of interest. O. A. received salary support from research funding paid to UCLA by Moderna, Inc. A. T. reports that this project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. C. L. G.’s institution received funding from the NIH for salary support for her role as site Principal Investigator for the Moderna Phase 3 trial and site Principle and Co-Chair for the Novavax Phase 3 trial. N. R. received research grants from Pfizer, Merck, Sanofi, Quidel, Immorna, Vaccine Company, and Lilly through her institution, consulting fees from Krog, honoraria as speaker for Virology education, and travel support from Sanofi and Moderna. N. R. serves on safety committees for ICON and EMMES and is a member of the Moderna, Sanofi, Seqirus, and Pfizer selected Advisory boards. I. H. is an employee of AstraZeneca and holds/may hold stock in AstraZeneca. A. R. F. reports grant support from Janssen, Pfizer, Moderna, CyanVac, VaxCo, and BioFire Diagnostics; advisory board fees from Arrowhead and GSK; travel reimbursement from GSK and Sanofi and fees for DSMB from Novavax. B. L. is an employee of Moderna, Inc. and may own stock/stock options in the company. J. S. declares support for the submitted work from the Janssen Pharmaceutical Companies of Johnson & Johnson and partial support (in the form of funding to his institution) from BARDA for the submitted work, declares support from the Janssen Pharmaceutical Companies of Johnson & Johnson and BARDA funding for part of this work, has patents on invention of the Janssen COVID-19 vaccine, and has Johnson & Johnson stock and stock options. P. A. G. reports a patent for a COVID-19 monoclonal antibody from Aridis Pharmaceuticals. V. C. reports payments made to Emory University from Gilead Sciences. K. N. receives grants from NIH to participate in overall organization of COVID vaccine trials and for participation in vaccine trials and has a grant for Vaxco for a phase 1 testing of a broadly reactive COVID-19 vaccine. L. D. is an employee of Novavax, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Probability of developing symptomatic coronavirus disease 2019 (COVID-19), full analysis set. Individuals with tempered immune systems (TIS) are plotted with non-TIS (NTIS) individuals who received placebo or vaccine through the blinded phase for each of the 4 trials: Moderna (A), AstraZeneca (B), Janssen (C), and Novavax (D).
Figure 2.
Figure 2.
Hazard ratios (HR) and vaccine efficacy (VE) for the full analysis set. A, HR and (B) VE for each trial for the symptomatic coronavirus disease 2019 (COVID-19) endpoint. C, HR and (D) VE for each trial for the severe COVID-19 endpoint. For HR (A and C), the participants receiving vaccine (solid black line) versus placebo (dashed black line) are described for each trial. For VE (B and D), participants with TIS (tempered immune system, purple) and non-TIS (green) are described for each trial. Please refer to Supplementary Table 5 for further details.
See this image and copyright information in PMC

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