Swiss army vaccines: a multipronged attack against SARS-CoV-2 and other betacoronaviruses
A nanoparticle vaccine, providing protection from up to eight viral receptor binding domains, is set to enter Phase I clinical trials after promising results in preclinical studies.
The 21st century has experienced three outbreaks of viral respiratory infections of global significance: the 2002 SARS-CoV, the 2012 MERS outbreak and the 2020 SARS-Cov-2. All three viruses have a shared genetic lineage and are part of the same subgroup of coronaviruses, known as betacoronaviruses. In response to the COVID-19 pandemic, caused by SARS-CoV-2, researchers around the world continue to work tirelessly to create potential treatments and vaccines to put an end to the rapid spread of the virus and the millions of deaths attributed to its associated illness.
One group from the California Institute of Technology (Caltech; CA, USA), has taken a forward-thinking approach to vaccine development. The team say that their nanoparticle vaccine can protect not only against COVID-19, but also against infections caused by future viruses that are similar to or alternative strains of SARS-CoV-2. They have paid particular attention to the fact that SARS-CoV-2 originated in animals and subsequently cross infected humans, as did all other major betacoronaviruses.
Lab leader Pamela Bjorkman described the rationale behind the study: “What we are trying to do is make an all-in-one vaccine protective against SARS-like betacoronaviruses regardless of which animal viruses might evolve to allow human infection and spread. This sort of vaccine would also protect against current and future SARS-CoV-2 variants without the need for updating.”
Like a Swiss army knife, with its multiple tools contained in one convenient unit, the nanoparticle is a molecular cage structure that can be loaded with up to eight appendages, each mimicking a unique respiratory binding domain (RBD). The RBD of a virus is the key it needs to gain access to and infect a host cell. When an immune system is exposed to these domains, it begins to develop antibodies, the protein molecules required to fight off future infections.
Individual strains of viruses may have RBDs that are unique and will therefore require different antibodies to successfully ward off infection. It is this fundamental difference between viral strains that makes the multipronged nanoparticles so advantageous; they are equipped with more tools to ready the body against multiple infections in a fashion that single-pronged vaccines are unable to do.
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Preliminary studies in mice yielded promising results. Genetically engineered mice, bred specifically to express a human receptor enabling them to be infected by coronaviruses, were used in the study. The mice were separated into three groups. The first group was injected with only the molecular cage of the nanoparticle. These mice acted as a negative control. The second group was loaded with homotypic nanoparticles, which contained only the SARS-Cov-2 RBD, acting as a positive control. The third group was injected with the eight-pronged nanoparticle (known as mosaic-8), containing the RBDs for 8 betacoronaviruses, including SARS-CoV-2.
Mice from each group were infected with either SARS-CoV-2 or SARS-CoV, which served as an analogue for future viral strains as mosaic-8 did not contain the RBD for SARS-CoV. In the first group, the unprotected mice were infected and ultimately killed by both viral strains. In the second group, while the vaccine did offer protection from SARS-CoV-2, it did nothing to protect the mice against infection by SARS-CoV. The third group, however, yielded no infections from either betacoronavirus, with both subsets of mice successfully fending off infection and displaying no signs of ill health. As mosaic-8 did not contain any protein relating to SARS-CoV, this was a promising proof of concept for the team.
These findings were further corroborated in non-human primate studies, with mosaic-8 displaying similar abilities in protecting rhesus macaques. Monkeys inoculated with mosaic-8 displayed little to no symptoms of infection from SARS-CoV or SARS-CoV-2 when compared to an unvaccinated control.
It is thought that mosaic-8 works by generating antibodies that target the areas of the RBDs that change the least between different betacoronaviruses. The positive control, containing only the SARS-CoV-2 RBD helps to support this hypothesis as they generated antibodies that targeted the most strain-specific regions of the binding domain.
With support from the Coalition for Epidemic Preparedness Initiative (CEPI; UK), mosaic-8 is expected to enter Phase I clinic trials soon. Bjorkman and colleagues hope to recruit primarily those who are either vaccinated or who have already been infected with SARS-CoV-2. CEO of CEPI, Richard Hatchett, is optimistic about mosaic-8 and the potential future implications that its success would have for vaccine technology. Hatchett explains, “The breakthrough exhibited in the Bjorkman lab study demonstrates huge potential for a strategy that pursues a new vaccine platform altogether, potentially overcoming hurdles created by new variants. I am delighted that CEPI will be supporting this novel approach to pandemic prevention in Phase I clinical trials.”
