UNMC teams exploring extended-release COVID vaccine

 A team of UNMC researchers developed a novel delivery platform for a “next generation” COVID vaccine. The vaccine is delivered through controlled, biodegradable, stable polymeric microspheres that permit the viral antigen to be released slowly over extended time periods to reduce the need for repeated boosters. 

The paper, published in Acta Biomaterialia, details the creation of the biodegradable polymeric microsphere. Proof of concept was tested with chemically inactivated SARS-CoV-2 proteins carried within the delivery formulation. These viral proteins, when encapsulated in the polymeric microspheres, induced robust antiviral immunity in animal models.

The viral antigen-loaded microsphere system can prevent the need for repeat immunizations, highlighting its potential as a unique vaccine delivery mechanism. “The idea of a single vaccine for SARS-CoV-2 without boosting can be realized if and when viral evolution can be accurately predicted,” said Howard Gendelman, MD, co-corresponding author of the paper and chair of the UNMC Department of Pharmacology and Experimental Neuroscience (PEN). “COVID is certainly going to be with us for quite a long time.”

Although still in an early stage, the study shows a path to predictive antiviral immunity through the development of a unique delivery system that could carry multiple viral antigens. “The new vaccine would serve to ameliorate the acquisition-based fatigue being seen in response to the frequent boosters needed to address SARS-CoV-2 virus evolution” said Bhavesh Kevadiya, PhD, co-corresponding author and a prior assistant professor in the PEN department.

The PEN department maintains itself as a world leader in the development, characterization and translation of long-acting drugs and vaccines for the treatment and prevention of viral diseases.

“We are in the beginning stages,” said Farah Shahjin, PhD, lead author and a former graduate student in PEN. “But we have a lot of options to move this forward. These approaches are the future of ameliorating the severity of COVID in the times ahead.”

The work served to demonstrate proof-of-concept for the successful loading and potential immunogenic responses to the whole, inactive SARS-CoV-2 virus-loaded microsphere. These results, in turn, offer the possibilities of future studies to optimize the process parameters to generate microsphere-borne viral antigens, as well as a long-term study of the immune responses against the antigen of interest, and therefore could provide the opportunity for developing a long-acting vaccine.

“The virus mutates. If we work to predict the mutations over a period of three or four years, we can plug that into a single vaccine. We can then use this system to deliver the vaccine formulated for the new, mutated virus we predict over a longer period of time, staying ahead of the virus and not reacting to it,” said Dr. Gendelman.

The study’s authors, which include current PEN graduate students Mahmudul Hasan and Milankumar Patel, posit that these injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. “The approach offers a means to reduce immunization frequency by predicting viral genomic variability,” the paper says. “This strategy could lead to longer-lasting antiviral protective immunity.”

The success in vaccine development follows a broader COVID vaccine initiative involving a novel modular vaccine platform through chemically synthesized peptides and bioinformatic target data, such as another study — by the teams of UNMC scientists led by Yuri Lyubchenko PhD, DSc, professor in pharmaceutical sciences, and Siddappa Byrareddy, PhD, professor and vice chair of research in PEN as co-corresponding authors — published in the journal Nanomedicine. “This second vaccine study is based on immunogen design that contains two defined B-cell epitopes from the spike glycoprotein of SARS-CoV-2 and the universal T-helper epitope PADRE,” said Dr. Byrareddy. In this study, the immunogens used were formulated by conjugation to gold nanoparticles, which elicited an IgG immune response and generated high virus-neutralizing titers.

A reviewer of the online publication summarized: “The translation of this well-targeted epitope vaccine, which can be highly accessible and affordable, enables protection with minimal stimulation of the immune system; this research could be revolutionary, not only for the COVID-19 pandemic and the variants of concern associated with this highly transmissible virus but also for all types of vaccines.”

The two studies taken together demonstrate the versatility of methods for future SARS-CoV-2 immune protection, although additional research still will need to be done before there is an application to humans.