Developing a Pan-Coronavirus Vaccine

Protection sought against SARS-CoV-2 variants and future coronavirus outbreaks. Cheryl Guttman Krader reports. The rapid development of COVID-19 vaccines is a stunning accomplishment that shows the power of science. But now there appears to be less efficacy against emerging variants of SARS-CoV-2. And what if there is a future pandemic caused by another type of coronavirus? Immunologist Dr Lbachir BenMohamed and colleagues are working to develop a pre-emptive pan-coronavirus vaccine. “Over the last 10 to 20 years, there has been an acceleration of emerging coronavirus diseases. Therefore, COVID-19 is not the first coronavirus pandemic, and it likely will not be the last,” Dr BenMohamed said. “Once the COVID-19 pandemic is behind us, we need to learn our lesson and do something today that will make us prepared for the future with a vaccine that will protect us from all coronaviruses.” DESIGN TARGETS The currently available COVID-19 vaccines are engineered to induce a B cell response with the development of antibodies to the spike protein found on the surface of SARS-CoV-2. A major limitation of this strategy is it focuses on the viral protein most subject to mutation, Dr BenMohamed said. “Although available COVID-19 vaccines recognise the spike protein with high affinity, the antibodies they induce will not be effective in neutralising viral variants with a mutated spike protein,” he explained. To circumvent that issue, Dr BenMohamed and colleagues are working to develop a vaccine based on additional antigenic targets that are both less prone to mutation and highly conserved among coronaviruses isolated from bats (the originating natural reservoir for all coronaviruses) and intermediate carrier animals. Applying immunoinformatics and sequence alignment approaches, they have identified seven epitope proteins that meet these criteria. These specific proteins are also highly conserved in all SARS-CoV-2 variants found among the more than 3.5 million available genome sequences. Another feature of the additional proteins is they are highly recognised by CD4+ and CD8+ T cells isolated from individuals who seem to have ‘natural protection’ against COVID-19, i.e., people who became infected with the virus (COVID-19 test positive) but were asymptomatic. “The currently available COVID-19 vaccines have a very minor effect on inducing CD4+ and CD8+ T cell responses. Optimal efficacy for neutralising and eliminating the virus depends on inducing all three arms of immunity,” Dr BenMohamed said. INITIAL EVIDENCE Preclinical research conducted using a transgenic mouse model as well as hamsters provides proof of principle for this approach developing a pan-coronavirus vaccine. In an initial study of a first candidate vaccine targeting one of the seven protein antigens, vaccinated animals exposed to multiple SARS-CoV-2 variants (including the original Wuhan virus and the mutated UK, delta, and South African variants) resisted infection, COVID-19-like disease, and survived. In contrast, 80% of control animals pretreated with a placebo vaccine died within six to seven days after virus exposure. Dr BenMohamed said that his group is now proceeding with testing the other six candidate vaccines. This research was presented at the AAO 2021 Retina Subspecialty Day in New Orleans, Louisiana, USA. Lbachir BenMohamed PhD is the Director of the Laboratory of Cellular and Molecular Immunology, Gavin Hebert Eye Institute, University of California, Irvine, USA. Dr BenMohamed founded a start-up biotechnology company named TechImmune, LLC at UC Irvine. The company will be responsible for a future clinical trial of a multi-antigen, pan-Coronavirus, vaccine-Coronavirus vaccine. lbenmoha@uci.edu