Findings suggest "mix-and-match" approach to boosters may be optimal
BOSTON – First detected in southern Africa in November 2021, United States health officials declared fast-spreading Omicron a COVID-19 variant of concern on December 1, 2021. Three weeks later, the highly-infectious variant – known as B.1.1.529 – had been detected in all 50 states and was the dominant variant in the United States. The Omicron variant has been shown to evade a substantial fraction of the neutralizing antibody responses induced by vaccines currently available, allowing breakthrough infections. However, in the recent surge of cases driven by the Omicron variant, the vaccines continued to protect against severe disease and hospitalization, suggesting that other immune mechanisms may be of critical relevance to long-term protection against COVID-19.
In a new study, scientists at Beth Israel Deaconess Medical Center (BIDMC) evaluated two of the current vaccines in macaques and found that they provided robust protection against the Omicron variant. The team's findings, published in the journal Cell, also suggest a possible advantage to heterologous (or "mix-and-match") prime-boost vaccine regimens.
Led by Dan H. Barouch, MD, PhD, director of the Center for Virology and Vaccine Studies at BIDMC, researchers vaccinated 30 macaques with either the two-dose BNT162b2 mRNA vaccine (manufactured by BioNTech and Pfizer) or the single-shot adenovirus vector-based Ad26.COV2.S vaccine (manufactured by Johnson & Johnson). Animals were boosted either with the same or different vaccine 14 weeks later.
Consistent with data from humans, the Pfizer vaccine induced a stronger antibody response, and the Johnson & Johnson vaccine induced a stronger CD8+ T cell responses. The booster shots increased neutralizing antibody levels detected in the blood.
"The different immune profiles induced by the mRNA and Ad26 vaccine platforms suggest possible advantages of heterologous prime-boost vaccine regimens for diversifying immune responses," said Barouch, who is also a professor of medicine at Harvard Medical School, and a member of the Ragon Institute of MGH, MIT, and Harvard.
When challenged with the Omicron variant, all of the vaccinated animals demonstrated breakthrough infections. However, viral loads were substantially lower in the vaccinated animals compared to the unvaccinated control groups and had mostly resolved in lung within four days. However, animals with moderate antibody levels but low levels of CD8+ T cells failed to control the viral infection in nasal swabs.
"Protection against severe disease may be different than protection against infection, and the importance of vaccine-elicited T cell responses may be greater for variants such as Omicron that largely escape antibody responses," said Barouch. "Taken together, our data suggest that protection against a highly-mutated SARS-CoV-2 variant involves the combination of humoral (antibody) and cellular immunity, and not neutralizing antibodies alone."
Co-authors included Abishek Chandrashekar, Jingyou Yu, Katherine McMahan, Catherine Jacob-Dolan, Jinyan Liu, Xuan He, David Hope, Tochi Anioke, Julia Barrett, Benjamin Chung, Nicole P. Hachmann, Michelle Lifton, Jessica Miller, Olivia Powers, Michaela Sciacca, Daniel Sellers, Mazuba Siamatu, Nahalee Surve, Haley VanWyk, Huahua Wan and Cindy Wu of BIDMC; Laurent Pessaint, Daniel Valentin, Alex Van Ry, Jeanne Muench, Mona Boursiquot, Anthony Cook, Jason Velasco, Elyse Teow, Mark G. Lewis and Hanne Andersen of Bioqual; Adrianus C.M. Boon of Washington University School of Medicine, Saint Louis; Mehul S. Suthar of Emory School of Medicine; Neharika Jain and Amanda J. Martinot of Tufts University Cummings School of Veterinary Medicine.
This work was supported by the National Institutes of Health (75N93021C00014, CA260476, 75N93021C00016) the Massachusetts Consortium for Pathogen Readiness, the Ragon Institute, and the Musk Foundation.
Barouch is a co-inventor on provisional vaccine patents (63/21,482; 63/133,969; 63/135,182). Please see the study for a full list of disclosures.
