IDCRC trial confirms safety of mix-and-match COVID-19 vaccine booster dosing
In adults who had previously received a full regimen of a COVID-19 vaccine approved or authorized by the Food and Drug Administration (FDA), an additional dose of any of these COVID-19 vaccines was safe and prompted an immune response. These are the results of a clinical trial by researchers from the Infectious Diseases Clinical Research Consortium (IDCRC). The preliminary clinical trial results were reported today in The New England Journal of Medicine. The ability to use COVID-19 vaccines for boosting that are different from those used for the primary series, “mix and matching,” can simplify vaccine booster administration.
These findings are from an ongoing Phase 1/2 trial led by the IDCRC and sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health, and informed the FDA’s recent recommendation to allow mix-and-match COVID-19 vaccine boosters.
The report describes findings from 458 adult volunteers who had been fully vaccinated with one of the three EUA COVID-19 vaccines at least 12 weeks prior to enrollment and who had no reported history of SARS-CoV-2 infection: 150 received a booster of Johnson & Johnson’s Ad26.CoV2-S vaccine; 154 received a booster of Moderna’s mRNA-1273 vaccine (100 mcg dose); and 154 received a booster of Pfizer-BioNTech’s BNT162b2.
The IDCRC trial, which began enrollment in May 2021, is led by principal investigators Robert L. Atmar, MD, of Baylor College of Medicine, Houston, TX, and Kirsten E. Lyke, MD, of the University of Maryland School of Medicine, Baltimore, MD.
“Mix-and-match is not a new approach – it is a well-known principle in vaccine science research. Mixing vaccine platforms can elicit a stronger, longer-lasting response than a single vaccine regimen and could help us fight variants,” says Dr. Lyke.
At 15 days after booster vaccination, serum antibody levels increased in all study groups, and leveled off by day 29. For a given primary EUA COVID-19 vaccine, administering a different vaccine as a booster elicited similar or higher serologic responses as compared to the same vaccine booster response. Additionally, T cell responses were measured. Cellular CD4 Th1 responses directed against the spike protein increased in all groups except volunteers who received a single dose of Johnson & Johnson followed by a booster of Johnson & Johnson. However, CD8 T cell responses were more durable in Johnson & Johnson recipients and those who received an mRNA primary series followed by Johnson & Johnson boost.
Booster vaccines may enhance waning immunity and expand the breadth of immunity against SARS-CoV-2 variants of concern. Mix-and-match prime-boost strategies may offer immunological advantages to optimize the breadth and longevity of protection achieved with currently available vaccines. They may also simplify the logistics of administering booster vaccines.
The trial participants kept diaries of any side effects and supplied blood samples on the day of booster vaccination and 15 days after boost. More than half of participants reported headache, pain at the injection site, muscle aches and malaise. There were no vaccine-related serious adverse events reported.
“These interim results cover only the initial (29 days) immune response to vaccine boost. We will continue to follow volunteers for a year to assess what impact boost vaccination has on longer-term immune responses. These data are providing safety and immunogenicity data regarding the feasibility of mixing different vaccine platforms as part of a vaccine booster strategy. Additional arms of the trial will test other candidate COVID-19 vaccines as the boosting vaccine,” says Dr. Atmar.
Participating IDCRC study sites:
- Baylor College of Medicine (BCM) Vaccine and Treatment Evaluation Unit (VTEU)
- Cincinnati Children’s Hospital Medical Center VTEU
- Emory University VTEU
- Kaiser Permanente Washington Health Research Institute VTEU
- New York University VTEU
- University of Maryland-Baltimore VTEU
- University of Pittsburgh, subsite of Vanderbilt VTEU
- University of Rochester VTEU
- University of Texas Medical Branch at Galveston, subsite of BCM VTEU
- University of Washington VTEU
NIAID grants supporting this research are UM1AI48372, UM1AI148373, UM1AI148450, UM1AI148452, UM1AI148573, UM1AI148574, UM1AI148575, UM1AI148576, UM1AI148684, UM1 AI148689 and with support from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00050.
About Infectious Disease Clinical Research Consortium (IDCRC)
The IDCRC, consisting of the Vaccine Treatment and Evaluation Units (VTEUs) and the IDCRC Leadership Group (under award number UM1AI148684), was formed in 2019 to support the planning and implementation of infectious diseases clinical research that efficiently addresses the scientific priorities of NIAID. The consortium includes infectious diseases leaders and clinical researchers from Emory University, University of Maryland School of Medicine, Baylor College of Medicine, Cincinnati Children’s Medical Center and University of Cincinnati, FHI360, Fred Hutchinson Cancer Research Center, Johns Hopkins University, Kaiser Permanente Washington Health Research Institute, New York University, Saint Louis University, Vanderbilt University Medical Center, University of Alabama at Birmingham, University of Rochester, University of Washington, other affiliated sites and NIAID.