Milestone reached in quest for universal coronavirus vaccine

UC Irvine scientists working on a pan-coronavirus vaccine have demonstrated in pre-clinical studies that combining their broad-based antigen approach with current COVID-19 vaccines gives better protection against illness from repeated infection by many virus variants.

“This is a significant milestone,” says virologist and immunologist Lbachir BenMohamed, PhD, a UCI professor and director of the Laboratory of Cellular and Molecular Immunology at the university’s Gavin Herbert Eye Institute. The eye-care provider has received four National Institutes of Health (NIH) grants to develop a vaccine to combat all coronaviruses, not just the one that causes COVID-19.

“We now have proof of concept that our novel and innovative vaccine approach offers broader protection against COVID-19 and longer-lasting immunity, even as new strains of the virus develop.”

In the nearly four years since SARS-CoV2 (severe acute respiratory syndrome coronavirus 2) first emerged in China in late 2019, the virus has continued mutating. New variants and strains have rendered existing vaccines less effective at preventing illness, confounding public health officials. New York health officials reported that 19% of fully vaccinated people in the state had experienced a breakthrough infection as of May 2023.

National policymakers have been calling on scientists to pursue the kind of research that BenMohamed’s team first embarked on in early 2020.

“The continued adverse effects of SARS-CoV-2 on individuals and populations necessitate the urgent development of the next generation of vaccines,” wrote the U.S. Food and Drug Administration’s Peter Marks, MD, PhD, in the Journal of the American Medical Association in late 2022.

In April, the White House announced Project Next Gen, a $5 billion program to speed development of new coronavirus vaccines and treatments.

Tapping into natural immunity

Current COVID-19 vaccines target the virus’ iconic spike protein, which mutates quickly. But the human immune system also reacts to dozens of other SARS-CoV-2 proteins.

BenMohamed and his team began their quest in early 2020, combing through 14 million genome sequences of animal and human coronaviruses for protein antigens that undergo far fewer mutations as the viruses evolve. They identified 10 such antigens that remain consistent across coronavirus variants, then studied these proteins in blood samples from asymptomatic COVID-19 patients, individuals who contracted the disease but had no symptoms.

“We identified the common antigens that remain highly conserved among different variants and are found to be selectively recognized by the immune system of people with asymptomatic COVID-19 cases,” the virologist says. “Because these antigens invoke the protective human immune response and keep people from experiencing any disease symptoms at all, they offer the greatest potential for new vaccines.”

Over the last year, he and his team discovered that the T-cell antigens they target not only protect against multiple variants of SARS-CoV-2, their benefit is even greater when added to the current vaccines that target the spike protein. Mice and hamsters treated with a combination of current vaccines and the UCI T-cell antigens were better protected from infection by the Delta strain as well as subsequent infection by the newer Omicron strain, which remains the dominant variant around the globe.

“If we can reduce illness and breakthrough infections, not only will the vaccine save lives, but it also will help stop the virus from spreading, both in humans and animals,” says BenMohamed. “To be truly effective, vaccines not only need to protect individuals from getting diseases, but also to protect the population from transmitting the disease from one person to another.

Moving toward clinical trials

The next step is to test their vaccine in a phase 1 clinical trial in humans. Before clinical trials can begin, however, they need to partner with a company to produce the vaccine, which will be based on the established mRNA lipid nanoparticle technology, a process BenMohamed says could take up to 18 months. If the vaccine proves safe, phase 2 and phase 3 trials would follow to validate its safety and efficacy.

The team’s research has been supported by a $3.7 million, five-year grant from the National Institute for Allergy and Infectious Diseases (NIAID) and seed funding from the Gavin Herbert Eye Institute. The university has filed three additional patents this year for a total of six related to the project.

To raise capital and ultimately bring a pan-coronavirus vaccine to market, BenMohamed co-founded TechImmune LLC, a partnership with the university, the eye institute and investors. TechImmune has raised an additional $2.5 million, including a $600,000 Small Business Innovation Research grant from the NIH.

Company president Jeffrey Ulmer, PhD, who has more than 30 years of experience in vaccine research and development with Novartis and GlaxoSmithKline, notes that seven groups of scientists at other research institutions are also working on universal coronavirus vaccines. But he believes the UCI team’s approach has distinct advantages because their data show that the immune system of asymptomatic COVID-19 patients selectively recognized their common T-cell antigens and the UCI project aims to confer broad spectrum, long-lasting protective immunity.

The COVID-19 pandemic created the largest global health crisis in a century. Before 2019, previous coronavirus outbreaks caused short-lived public health crises in 2003, 2008, 2012. The disease continues to persist with new variants emerging around the world despite widespread use of current spike-based vaccines.

BenMohamed points out that SARS-CoV-2 is unlikely to be the last coronavirus to cause widespread disease. He hopes that his lab’s vaccine approach will make it possible to respond quickly with effective therapies when the need arises.

“Developing the next generation, pre-emptive coronavirus vaccine is about much more than the current pandemic,” he says. “Our ultimate goal is to prevent and be better prepared to swiftly respond to future global pandemics.”