What to know about the next generation of COVID-19 vaccines

The first phase of human trials studying a possible nasal COVID-19 vaccine has opened, the National Institutes of Health (NIH) announced.

The clinical trial, sponsored by the federal health agency, is enrolling participants at three sites across the U.S.

Researchers believe the vaccine candidate may provide even better protection against emerging variants than the COVID vaccines given via injection.

"The concept is that we're looking for next generation vaccines," said Dr. John Brownstein, an epidemiologist and chief innovation officer at Boston Children's Hospital and an ABC News contributor. "Throughout the pandemic, we had the incredible scientific breakthrough of COVID vaccines that happened, that got into production incredibly quickly and were safe and effective. But of course, we also recognize that there are challenges of the existing vaccines."

Here's what you need to know about the nasal COVID-19 vaccine clinical trial now underway:

What is the new vaccine candidate?

The candidate, MPV/S-2P, uses a live-weakened version of a virus called murine pneumonia virus (MPV), which does not cause disease in humans.

MPV will deliver a stabilized version of the spike protein, which the SARS-CoV-2 virus, that causes COVID-19, uses to attach and infect human cells. This will teach the body to recognize the protein and train immune cells to attack if a person is infected.

Pre-clinical trials in non-human primates found MPV/S-2P to be safe and well-tolerated and that it produced a robust immune response, both in SARS-CoV-2 antibodies and in the epithelial cells that line the nose and respiratory tract.

"Viruses like SARS-CoV-2 come into the body through the nose, into the lungs and then gets integrated into our bloodstream and disseminated through the body," Dr. Reynold Panettieri, a professor of medicine at the Robert Wood Johnson Medical School at Rutgers University, told ABC News.

"What we realized is that systemic vaccination -- when we inject it and it goes through the body to build up immunity -- is not as effective as generating a mucosal, or lining cell, immunity in the nose or in the lungs," he said. "And so, when people can inhale the protein, in this case, the spike protein ... it actually builds up an immune response that's much more robust than that when it is injected."

Challenges with the current vaccine

In December 2021, the U.S. Food and Drug Administration (FDA) authorized two new messenger RNA (mRNA) COVID-19 vaccines, from Pfizer-BioNTech and from Moderna, to target the original variant.

While most vaccines use a weakened or inactivated virus to stimulate an immune response, mRNA vaccines teach the body how to make proteins that can trigger an immune response and fight off an infection.

Because researchers can design mRNA vaccines more quickly than they can produce the live or weakened pathogens needed for a traditional vaccine, mRNA vaccines against COVID-19 were quickly developed, tested, mass produced and delivered to the general population, preventing millions of hospitalizations and deaths, according to analyses.

Both have been updated over time to target new variants including in September 2022 to target both the original variant and BA.4 and BA.5 – offshoots of the omicron variant -- and in September 2023 to target the XBB offshoot of the omicron variant. Only the latter is currently in use.

"The current vaccines have diminished efficacy over time," Brownstein said. "These vaccines were highly protective against severe COVID hospitalizations and deaths, [but] it wasn't as effective at slowing cases and preventing transmission."

Additionally, mRNA vaccines require a multi-step process to manufacture as well as ultra-cold storage, which can present logistical challenges. Further, some people may not want to receive mRNA vaccines because they are averse to needles.

"Nasal spray is often more often more accepted by a population, so if it's a less concerning mode of delivery, plus it offers better protection, plus it offers potentially better storage and distribution potential, it highlights that this could be a really important new step in controlling this virus," Brownstein said.

How will the trial work?

The clinical trial will enroll 60 healthy adult participants between ages 18 and 64 who received at least three doses of an MRNA COVID-19 vaccine approved or authorized by the FDA.

There will be several trial sites including at Baylor College of Medicine in Houston Texas; The Hope Clinic of Emory University in Decatur, Georgia; and New York University Grossman Long Island School of Medicine in Long Island.

Participants will be split into three groups, each receiving different dosages. Researchers will follow-up with the volunteers seven times over the course of a year and measure if the vaccine is safe and if it produces an immune response in the nose and in the blood.

Because clinical trials take time to produce data and require at least three phases before being submitted for FDA authorization, experts say it's unlikely these vaccines will be available in fall 2024.

"Early in the pandemic, we were moving quicker than usual to get a get a vaccine out there," Panettieri said. "Not that any steps were skipped, but we needed to save lives."

Because a COVID-19 infection now results in mild symptoms for most healthy people, "we do have time to actually go through the typical process the FDA takes to approve a new therapy," he added. "That is going to help everyone. It's going to be making sure it's safe and effective."

Dr. John Beigel, associate director for clinical research in the National Institute of Allergy and Infectious Diseases' (NIAID) division of microbiology and infectious diseases, told ABC News that MPV/S-2P falls under Project NextGen.

The project, led by the Biomedical Advanced Research and Development Authority (BARDA) and the NIAID, plans to support 15 next generation vaccines into Phase 1 clinical trials, of which MPV/S-2P is the first.