Optimized second-generation mRNA vaccine demonstrated improved protection against COVID-19 in preclinical testing

BOSTON – In a recent phase 2b/3 clinical trial, a third mRNA vaccine against COVID-19 — known as CVnCoV and developed by CureVac — reported approximately 48 percent efficacy against symptomatic disease. In a head-to-head test of a revised version of the vaccine, CV2CoV, researchers at Beth Israel Deaconess Medical Center (BIDMC) assessed the vaccines’ ability to provoke an immune response as well as their protective efficacy against COVID-19 in non-human primates. Their findings, published in Nature, show the modifications made to the second-generation CV2nCoV induced a ten-fold higher antibody response than the original version, CVnCoV.

“We found that CV2CoV elicited substantially higher immune responses and provided significantly improved protective efficacy against SARS-CoV-2, the virus that causes COVID-19, compared with CVnCoV in macaques,” said Dan H. Barouch, MD, PhD, director of the Center for Virology and Vaccine Research at BIDMC and professor of medicine at Harvard Medical School. “These data suggest that optimizing selected elements of the mRNA backbone can substantially improve the immunogenicity and protective efficacy of mRNA vaccines.”

Barouch and colleagues' data revealed that, while CVnCoV provided only modest reduction in viral loads in immunized animals later challenged with SARS-CoV-2, CV2CoV induced ten-fold higher antibody responses and dramatically lowered viral loads. They also report that CV2CoV induced antigen-specific memory B cell responses and T cell responses. Moreover, CV2CoV raised similar antibody titers in macaques compared with the BNT162b2 vaccine developed by Pfizer.

“The improved characteristics of CV2CoV compared with CVnCoV may translate into increased efficacy in humans, and clinical trials of the second-generation vaccine are planned,” said Barouch, who is also a member of the Ragon Institute of MGH, MIT and Harvard.

Co-authors included Makda S. Gebre, Jingyou Yu, Abishek Chandrashekar, Noe B. Mercado, Xuan He, Jinyan Liu, Katherine McMahan, Tori Giffin, David Hope, Shivani Patel, Daniel Sellers, Owen Sandborn, Julia Barrett, Xiaowen Liu and Andrew C. Cole of BIDMC; Susanne Rauch, Nicole Roth, Stefan O. Mueller and Benjamin Petsch of Harvard Medical School; Amanda Minot of Tufts University Cummings School of Veterinary Medicine; David R. Martinez and Ralph S. Baric of University of North Carolina at Chapel Hill; Laurent Pessaint, Danile Valentin, Zack Flinchbaugh, Jake Yalley-Ogunro, Jeanne Muench, Renita Brown, Anthony Cook, Elyse Teow, Hanne Andersen and Mark G. Lewis of Bioqual; Adrianus C.M. Boon of Washington University School of Medicine.

This work was supported by CureVac AG and the German Federal Ministry of Education and Research (BMBF; 01KI20703), the National Institutes of Health (CA260476), the Massachusetts Consortium on Pathogen Readiness, and Ragon Institute of MGH, MIT, and Harvard. Development of CV2CoV is carried out in a collaboration of CureVacAG and GSK. Please see the paper for a complete list of disclosures.