Two COVID-19 mRNA vaccines, made by BioNTech/Pfizer and Moderna, are helping to change the course of the COVID-19 pandemic. A third mRNA vaccine, developed by CureVac and known as CVnCoV, has not had the same success to date. Indeed, a recent phase IIb/III clinical trial of CVnCoV reported approximately 48% efficacy against symptomatic disease.

Now, a second generation mRNA vaccine has been developed, named CV2CoV, with noncoding modifications to optimize the vaccine. Researchers at Beth Israel Deaconess Medical Center (BIDMC) conducted a head-to-head study of CV2CoV compared with CVnCoV in nonhuman primates. The scientists assessed the vaccines’ ability to provoke an immune response as well as their protective efficacy against COVID-19 in non-human primates.

“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.”

Their findings are published in Nature in the paper, “Optimization of Non-Coding Regions for a Non-Modified mRNA COVID-19 Vaccine.

The researchers immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham. CV2CoV, they write, “induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV.”

The 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.

In addition, CV2CoV induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including the delta variant. And, while CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV had “more robust protection with markedly lower viral loads in the upper and lower respiratory tract.”

“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.