A Phase 2 clinical trial evaluating various additional COVID-19 booster shots has begun enrolling adult participants in the U.S. The trial aims to understand if different vaccine regimens — prototype and variant vaccines alone and in combinations — can broaden immune responses in adults who already have received a primary vaccination series and a first booster shot.
The study, known as the COVID-19 Variant Immunologic Landscape (COVAIL) trial, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The trial is funded through a contract (75N91019D00024) to Frederick National Laboratory for Cancer Research, operated by Leidos Biomedical Research in Frederick, Maryland.
Kaiser Permanente Washington Health Research Institute (KPWHRI) is one of 24 clinics across the country participating in the trial.
“KPWHRI has begun enrolling previously vaccinated participants who have or have not had prior SARS-CoV-2 infection,” said Lisa A. Jackson, MD, MPH, who is leading the trial at KPWHRI. “Participants who’ve previously received three doses will receive a fourth dose as part of this trial.”
Despite waning protection against infection and mild illness during the Omicron wave, COVID-19 vaccines available in the U.S. so far have maintained durable protection against severe COVID-19. However, NIAID is preparing for the possibility of future variants evading protection against currently available COVID-19 vaccines.
COVID-19 vaccine manufacturers can adjust prototype vaccines to target specific variants, a process similar to how manufacturers update seasonal influenza vaccines every year to target circulating strains. However, predicting if, when, and where new COVID-19 variants will emerge and how they will affect the population, remains challenging. Studies indicate that Omicron has a combination of mutations that make it substantially different from prior SARS-CoV-2 variants. Should a new variant emerge that more closely resembles ancestral SARS-CoV-2 or, for example, the Delta variant, an Omicron-specific vaccine may not offer substantial protection. An individual’s response to booster shots may also be impacted by their history of prior infection and vaccination, or both, and what type of COVID-19 vaccines they received.
Vaccine manufacturers have previously studied some variant vaccine candidates and are currently conducting clinical trials of Omicron-specific vaccines. The COVAIL trial will gather data on the immune responses induced by prototype vaccines and variant vaccine candidates — including bivalent vaccines, which target two SARS-CoV-2 variants — to inform booster shot recommendations.
Nadine Rouphael, MD, director of the Hope Clinic at the Emory Vaccine Center in Atlanta, and Angela Branche, MD, associate professor of medicine at the University of Rochester Medical Center in New York, are leading the trial. Site investigators at 24 clinics are enrolling 600 participants 18 years and older who already have received a primary COVID-19 vaccination series and booster shot. Participants are randomly assigned to one of six vaccine regimens:
The trial will be adapted to enroll more participants to evaluate additional vaccine platforms and variant vaccines from other manufacturers as needed to further inform public health decisions. Participants will be monitored for symptoms and adverse events following vaccination and will be asked to return to the clinic during set times over the course of 12 to 14 months to provide blood samples. Investigators will evaluate the samples in the laboratory to measure and characterize immune responses to SARS-CoV-2 strains. Investigators aim to have initial findings available by August 2022.
The study is being conducted in collaboration with academic medical centers across the U.S., NIAID’s Infectious Diseases Clinical Research Consortium (IDCRC) and the NIAID SARS-CoV-2 Assessment of Viral Evolution (SAVE) Program. For more information about the trial, including specific site locations, and for details on how to participate, please visit clinicaltrials.gov and search identifier NCT05289037.
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