Next-generation COVID-19 vaccine presents promising results in mice

Studies conducted in mice have shown that the COVID-19 vaccine being developed by researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil is safe and efficacious. The vaccine triggered a satisfactory immune response against the pathogen in the mice and protected them from infection. An article describing the results is published in the journal Scientific Reports.

“Most vaccines are based on attenuated or inactivated viruses, but our next-generation strategy enables us to prioritize not just safety and efficacy but also plasticity in the formulation so that the vaccine can easily be updated to combat variants of concern,” said Gustavo Cabral de Miranda, principal investigator for the project, hosted by the Immunology Laboratory in the Institute of Tropical Medicine (IMT-FM-USP).

The strategy used by the researchers at FM-USP to develop the vaccine deploys virus-like particles (VLPs). “VLPs have similar characteristics to viruses but without viral genetic material, so although they’re recognized by the immune system, they cannot replicate or cause disease,” Cabral said.

VLPs can serve as vaccines on their own, or they can be conjugated with an antigen (a protein that stimulates the immune system to produce antibodies), as in this specific case.

“Under certain conditions in the lab, structural surface proteins are capable of converting themselves into VLPs. They can be produced in the lab using bacteria that act as miniature factories to stimulate this transformation. A second step entails inoculation of the antigen, which is the spike protein in the case of COVID-19. This facilitates the entire process, makes it flexible, and lowers the cost of developing the vaccine,” he said.

Another advantage of the COVID-19 vaccine, according to Cabral, is that it does not require an adjuvant to enhance the body’s immune response to the antigen. “In both the in vitro and in vivo tests, we designed strategies to keep the cost of formulation low and use the smallest possible amount of inputs not developed in our own lab. The vaccine doesn’t require an adjuvant, for example,” he said.

Besides part of the virus they are designed to combat, or molecules that mimic the virus such as VLPs, vaccines contain various other compounds that stimulate the immune response, especially adjuvants. The most common adjuvant is aluminum hydroxide, which has been used in vaccines worldwide for more than 100 years.

“Opting for the development of a self-adjuvanted vaccine enables us to avoid dependency on the companies that produce adjuvants and lowers the cost of the formulation,” he said.

The group of researchers at FM-USP aims to produce knowledge for use by a platform that can develop several other vaccines. “VLPs constitute a highly flexible technology. In this case, for example, we can simply remove the antigen [a piece of the SARS-CoV-2 spike protein] and replace it with a protein from zika virus,” Cabral explained.

“There’s nothing hypothetical about this example. We’re developing such a vaccine at our lab. It’s no simple task, of course, but a platform for the development of several vaccines can be based on this technology.”