Wistar Scientists Behind the Next Wave of COVID-19 Vaccines

Current COVID-19 vaccines were created in record time, but scientists are working to make better, longer lasting vaccines that could be used around the world.

The first generation of COVID-19 vaccines have been highly effective, but also have limitations: their efficacy can wane without a booster shot, and they may be less effective against some variants. Now scientists at The Wistar Institute have developed a more targeted vaccine that, in animal studies, shows stronger, broader, and more durable protection in a single, lower dose.

“This is among the first second-generation vaccines that will have more advanced features and broader protection,” said Daniel Kulp, Ph.D., associate professor in the Vaccine & Immunotherapy Center and corresponding author of the study.

The vaccine combines three technologies — immune focusing, self-assembling nanoparticles, and DNA delivery — into a single platform for the first time.

Immune focusing means that researchers engineered an immunogen that targets specific areas of COVID’s famous “spike” protein to generate protective antibodies. Instead of replicating the whole structure, this immunogen blocks specific sites that produce non-neutralizing antibodies. This stimulates higher production of neutralizing antibodies — the kind of antibodies that help the immune system fight the virus.

Having higher levels of these important antibodies can reduce the chance that the vaccine’s effectiveness will wane over time.

Studies in mice found that 100% of animals who received a single dose of the new vaccine were protected from death after virus challenge, whereas only 20% of animals receiving the first-generation vaccine were protected.

Nanovaccines consist of extremely small (nano) particles—similar in size to bacteria and viruses—used to display multiple copies of an antigen and able to elicit strong immune responses. The new vaccine also uses DNA to instruct cells to make these vaccines. Kulp noted that DNA vaccines can be stored at room temperature, making it potentially easier to transport to remote or developing locations than existing approved vaccines (such as mRNA vaccines), which require specialized cold storage. DNA vaccines historically also have an excellent safety profile, with a very low chance of eliciting severe adverse effects amongst clinical trial participants.

“Current vaccine effects on reducing transmission of SARS-CoV-2 variants of concern including Delta and Omicron could be improved for their breadth of protection as well as their immune potency,” said co-author David B. Weiner, Ph.D., executive vice president, director of the Vaccine & Immunotherapy Center and the W.W. Smith Charitable Trust Professor in Cancer Research, at The Wistar Institute.

The scientists are seeking funding and partnership to begin human trials of the new vaccine.

Dr. Kulp’s research was made possible through the generous support of Wistar donors who contributed to this project through the Wistar Coronavirus Discovery Fund.