A potential new vaccine developed by members of the Duke Human Vaccine Institute has been shown to be effective in protecting monkeys and mice against a variety of coronavirus infections – including SARS-CoV-2 as well as SARS-CoV-1 original and associated bat coronaviruses that could potentially cause the next pandemic.
The new vaccine, called the pan-coronavirus vaccine, triggers neutralizing antibodies via a nanoparticle. The nanoparticle is made up of the coronavirus part that allows it to bind to cell receptors in the body and is formulated with a chemical booster called an adjuvant. Success in primates is very relevant to humans.
The results appear Monday, May 10 in the newspaper Nature.
“We started this work last spring knowing that, like all viruses, mutations would occur in the SARS-CoV-2 virus, which causes COVID-19,” said lead author Barton F. Haynes, MD, director of the Duke Human Institute for Vaccines (DHVI). “The mRNA vaccines were already in development, so we were looking for ways to maintain their effectiveness once these variants emerged.
“This approach not only provided protection against SARS-CoV-2, but the vaccine-induced antibodies also neutralized variants of concern originating in the UK, South Africa and Brazil,” said Haynes. “And the induced antibodies reacted with quite a large panel of coronaviruses.”
Haynes and his colleagues, including lead author Kevin Saunders, Ph.D., director of research at DHVI, drew on previous studies involving SARS, the respiratory disease caused by a coronavirus called SARS-CoV-1. They found that a person infected with SARS had developed antibodies capable of neutralizing several coronaviruses, suggesting that a pan-coronavirus might be possible.
The Achilles heel of coronaviruses is their receptor binding domain, located on the tip that connects viruses to receptors in human cells. Although this binding site allows it to enter the body and cause infection, it can also be targeted by antibodies.
The research team has identified a particular receptor-binding domain site present on SARS-CoV-2, its circulating variants, and SARS-related bat viruses, which makes them highly vulnerable to cross-neutralizing antibodies.
The team then designed a nanoparticle displaying this vulnerable point. The nanoparticle is combined with a small molecule adjuvant – specifically, the toll-type 7 and 8 receptor agonist called 3M-052, formulated with alum, which was developed by 3M and the Infectious Disease Research Institute . The adjuvant stimulates the body’s immune response.
In tests of its effect on monkeys, the nanoparticle vaccine blocked COVID-19 infection by 100%. The new vaccine also caused significantly higher levels of neutralization in animals than current vaccine platforms or natural infection in humans.
“Basically what we did was take multiple copies of a small part of the coronavirus for the body’s immune system to respond to them in an increased way,” Saunders said. “We found that not only did this increase the body’s ability to prevent the virus from causing infection, but it also targeted this cross-reacting vulnerability site on the spike protein more frequently. We believe that is why this vaccine is effective against SARS-CoV. -1, SARS-CoV-2 and at least four of its common variants, plus additional animal coronaviruses. “
“There have been three coronavirus outbreaks in the past 20 years, so there is a need to develop effective vaccines that can target these pathogens before the next pandemic,” Haynes said. “This work represents a platform that could prevent, quickly temper or extinguish a pandemic.
Besides Haynes and Saunders, study authors include Esther Lee, Robert Parks1,5, David R. Martinez, Dapeng, Haiyan Chen, Robert J. Edwards, Sophie Gobeil, Maggie Barr, Katayoun Mansour, S. Munir Alam, Laura L. Sutherland, Fangping Cai, Aja M. Sanzone, Madison Berry, Kartik Manne, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Anyway B. Kapingidza, Mihai Azoitei, Longping V. Tse, Trevor D. Scobey, Rachel L. Spreng, R. Wes Rountree, C. Todd DeMarco, Thomas N. Denny, Christopher W. Woods, Elizabeth W. Petzold, Thomas H. Oguin III, Gregory D. Sempowski, Matthew Gagné, Daniel C Douek, Mark A. Tomai, Christopher B. Fox, Robert Seder, Kevin Wiehe, Drew Weissman, Norbert Pardi, Hana Golding, Surender Khurana, Priyamvada Acharya, Hanne Andersen, Mark G. Lewis, Ian N. Moore, David C. Montefiori and Ralph S. Baric.
The study received funding from the State of North Carolina with federal CARES law funds; the National Institutes of Health (AI142596, R01AI157155 U54 CA260543, F32 AI152296, T32 AI007151); the North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill with funding from the North Carolina Coronavirus Relief Fund; and a Burroughs Wellcome Fund Postgraduate Enrichment Scholarship.