The University of California San Diego has joined a Phase II clinical trial to evaluate various additional COVID-19 booster shots. The trial seeks to understand if different vaccine regimens 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 trial or COVAIL 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 to Frederick National Laboratory for Cancer Research, operated by Leidos Biomedical Research (75N91019D00024) in Frederick, Maryland.
Despite waning protection against infection and mild illness during the Omicron wave, COVID-19 vaccines available in the United States have thus far maintained durable protection against severe COVID-19. The concern is that future variants may evade protection provided by currently available COVID-19 vaccines.
COVID-19 vaccine manufacturers can adjust their 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.
"The emergence of SARS-CoV-2 variants has challenged the efficacy of available preventive vaccines. It’s clear that we need to learn more about how we might adapt vaccines to match circulating variants and expand and optimize immune coverage to existing and emerging variants," said Susan Little, MD, professor of medicine at UC San Diego School of Medicine and principal investigator of the UC San Diego trial site.
"The COVAIL study will evaluate the safety and immunogenicity of additional doses of prototype and variant vaccine candidates in previously vaccinated participants with or without prior SARS-CoV-2 infection. It will evaluate innate, cellular and humoral (the presence of antibodies in blood) immune responses to inform on how to shift the immune response to cover new variants as they emerge."
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.
Researchers at the Emory Vaccine Center in Atlanta and at the University of Rochester Medical Center in New York are leading the trial. UC San Diego is one of 24 academic medical centers around the country enrolling 600 participants. Adults, 18 years and older, who have already received an FDA-authorized/approved primary COVID-19 vaccination series and a booster shot and are in generally good health may be eligible. Participants are randomly assigned to one of six vaccine regimens:
The trial is slated to run four years and can expand to enroll 1,500 participants nationwide.
Study vaccines included in this first stage of the trial are manufactured by Moderna, Inc. in Cambridge, Mass. The trial will be adapted to enroll more participants to evaluate additional vaccine platforms and variant vaccines from other manufacturers as needed. 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 NIAID’s Infectious Diseases Clinical Research Consortium and the NIAID SARS-CoV-2 Assessment of Viral Evolution Program. clinicaltrials.gov.