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Invited Commentary
Public Health
November 2, 2021

Single-Dose Ad26.COV2.S Vaccine—Room for Improvement

Author Affiliations
  • 1Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore
  • 2Department of Medicine, Baltimore Veterans Affairs Medical Center, Baltimore, Maryland
JAMA Netw Open. 2021;4(11):e2133012. doi:10.1001/jamanetworkopen.2021.33012

The development and deployment of vaccines to prevent SARS-CoV-2 infection have been a major focus of the response to the COVID-19 pandemic. Now that these vaccines are widely available, the next important step is to assess real-world vaccine effectiveness (VE), especially against evolving variants of the virus. Comparing VE provides useful data for decision-makers to adjust public health policy based on the vaccines’ performance, and it also can be considered a valuable source for gaining public trust.

Compared with the messenger RNA (mRNA)–based vaccines, the Ad26.COV2.S vaccine (Johnson & Johnson) has been administered less often; concurrently, there are fewer data on VE for this vaccine. Corchado-Garcia et al1 provide valuable data for the real-world effectiveness of the Ad26.COV2.S vaccine in an observational, retrospective, comparative effectiveness research study. This study consisted of 8889 vaccinated and 88 898 unvaccinated individuals, with matching based on age, sex, zip code, race, ethnicity, and previous number of SARS-CoV-2 polymerase chain reaction tests. The authors found that the VE of the Ad26.COV2.S vaccine was 73.6%, which is in accordance with the effectiveness of 66.9% reported in the phase 3 clinical trial of this vaccine.2 In addition, the study by Corchado-Garcia et al1 shows that the Ad26.COV2.S vaccine reduces the risk of hospitalization and intensive care unit admission.

The emergence of new variants of SARS-CoV-2 has raised concerns about immune evasion and reduced VE of vaccines that are developed based on the Wuhan strain. The study by Corchado-Garcia et al1 is part of a growing body of work surrounding humoral responses to a single dose of the Ad26.COV2.S vaccine and VE. Several studies have showed that the recipients of the Ad26.COV2.S vaccine have lower neutralization activity against virus variants.3,4 In terms of VE, 2 studies have shown that the effectiveness of the Ad26.COV2.S vaccine is stable over time (before and after the emergence of the Delta variant), with a moderate decrease in effectiveness for individuals older than 75 years.5,6 The emergence of the Delta variant occurred in the final weeks of the study by Corchado-Garcia et al1; thus, there were not enough cases to determine VE against this variant.

What is becoming more clear with time is that the single-dose regimen of the Ad26.COV2.S vaccine seems to be inferior to the mRNA-based vaccines in terms of VE. Data from the original clinical trials point to a VE of 66.9% with the Ad26.COV2.S vaccine, 95% with the BNT162b2 vaccine (Pfizer/BioNTech),7 and 94.1% with the mRNA-1273 vaccine (Moderna).8 Although the definitions and methods of these studies were different, the same trend was noted in 2 studies by the same group, 1 of which is the study by Corchado-Garcia et al1 in the current issue of JAMA Network Open. Based on the second study by the same group, the VE against infection is 86.1% with the BNT162b2 vaccine and 93.3% with the mRNA-1273 vaccine,9 which is significantly higher than the 73.6% real-word effectiveness of the Ad26.COV2.S reported by Corchado-Garcia et al.1 Regarding VE against the Delta variant, a recent study by the Centers for Disease Control and Prevention shows that VE was 95% with the mRNA-1273 vaccine, 60% with the BNT162b2 vaccine, and 60% with the Ad26.COV2.S vaccine.5

Based on the recent findings of Corchado-Garcia et al,1 as well as the growing body of literature, it appears that the single-dose Ad26.COV2.S vaccine, although providing protection against infection and serious disease in most recipients, still has room for improvement. This may ultimately come in the form of a second dose of the same vaccine, as reported recently (increasing VE to 94%, per the manufacturer),10 or potentially by boosting the Ad26.COV2.S vaccine with another vaccine (mRNA or protein based).

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Article Information

Published: November 2, 2021. doi:10.1001/jamanetworkopen.2021.33012

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Tehrani ZR et al. JAMA Network Open.

Corresponding Author: Mohammad M. Sajadi, MD, Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, 725 W Lombard St (N548), Baltimore, MD 21201 (msajadi@ihv.umaryland.edu).

Conflict of Interest Disclosures: None reported.

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