Spray or shot?
By Washington University School of Medicine
The
rapid development of COVID-19 vaccines within months of the virus’s
emergence was a remarkable achievement of modern science, saving millions of
lives. But for all the good they did in reducing illnesses and deaths, the
shots were unable to end the pandemic because of one notable weakness: They
couldn’t stop the spread of the virus.
A new study by researchers at Washington University School of Medicine in St. Louis indicates that next-generation vaccines that target the virus’s points of entry — the nose and mouth — may be able to do what traditional shots cannot: contain the spread of respiratory infections and prevent transmission.
Using a nasal
COVID-19 vaccine based on Washington University technology, approved for use in
India and licensed to Ocugen for further development in the U.S., the
researchers showed that vaccinated hamsters that developed infections did not
pass the virus on to others, breaking the cycle of transmission. In contrast,
an approved COVID-19 vaccine that is injected failed to prevent the spread of
the virus.
Efficacy of Mucosal Vaccines
The
findings, published July 31 in Science Advances, provide further
evidence that so-called mucosal vaccines sprayed into the nose or dropped into
the mouth may be the key to controlling respiratory infections such as
influenza and COVID-19 that continue to circulate and cause significant illness
and death.
“To
prevent transmission, you need to keep the amount of virus in the upper airways
low,” said senior author Jacco Boon, PhD, a professor of medicine, of molecular
microbiology and of pathology & immunology. “The less virus that is there
to begin with, the less likely you are to infect someone else if you cough or
sneeze or even just breathe on them. This study shows that mucosal vaccines are
superior to injected vaccines in terms of limiting viral replication in the
upper airways and preventing the spread to the next individual. In an epidemic
or pandemic situation, this is the kind of vaccine you’re going to want.”
Developing vaccines that can control virus levels in the nose has proven challenging. Viruses such as influenza virus, SARS-CoV-2 (the virus that causes COVID-19), and respiratory syncytial virus (RSV) multiply rapidly in the nose and spread from person to person within a few days of initial exposure. Traditional injectable vaccines generate immune responses that can take a week to build to full strength and are much less potent in the nose than in the bloodstream, leaving the nose relatively unprotected against a fast-multiplying, fast-spreading virus.
In
principle, a vaccine sprayed or dropped directly into the nose or mouth could
limit viral reproduction and thereby reduce transmission by eliciting an immune
response right where it’s needed most. But gathering evidence that mucosal
vaccines actually do reduce transmission has proven tricky. Animal models of
transmission are not well-established, and tracking person-to-person
transmission is fiendishly complicated, given the number and variety of
encounters a typical person has on any given day.
For
this study, Boon and colleagues developed and validated a model for community
transmission using hamsters and then used it to assess the effect of mucosal
vaccination on the spread of SARS-CoV-2. (Unlike mice, hamsters are naturally
susceptible to infection with SARS-CoV-2, making them the ideal laboratory
animals for a transmission study.)
Study Methodology and Findings
The
researchers immunized groups of hamsters with laboratory versions of approved
COVID-19 vaccines: the nasal iNCOVACC used in India or the injected Pfizer
vaccine. For comparison, some hamsters were not immunized. After giving the
vaccinated hamsters a few weeks for their immune responses to fully mature, the
researchers infected other hamsters with SARS-CoV-2 and then placed the
immunized hamsters with the infected hamsters for eight hours. This first step
of the experiment mimics the experience of vaccinated people who are exposed to
a person with COVID-19.
After
spending eight hours rubbing shoulders with infected hamsters, most of the
vaccinated animals became infected. Virus was found in the noses and lungs of
12 of 14 (86%) hamsters that had received the nasal vaccine, and 15 of 16 (94%)
hamsters that had received the injected vaccine. Importantly, while most
animals in both groups were infected, they weren’t infected to the same degree.
Hamsters that had been nasally immunized had virus levels in the airways 100 to
100,000 times lower than those that had received the shot or had not been
vaccinated. The study did not assess the animals’ health, but previous studies
have shown that both vaccines reduce the likelihood of severe illness and death
from COVID-19.
The
second step of the experiment yielded even more striking results. The
researchers took vaccinated hamsters that subsequently developed infections and
placed them with healthy vaccinated and unvaccinated hamsters for eight hours
to model transmission of virus from a vaccinated person to others.
None
of the hamsters that were exposed to nasally vaccinated hamsters became
infected, regardless of whether the recipient hamster had been vaccinated or
not. In contrast, roughly half of the hamsters that were exposed to hamsters
vaccinated by injection became infected — again, regardless of the recipient’s
immunization status. In other words, vaccination through the nose — but not by
injection — broke the cycle of transmission.
These data, Boon said, could be important as the world prepares for the possibility that avian influenza, currently causing an outbreak in dairy cows, might adapt to humans and trigger a flu epidemic. An injectable vaccine for avian influenza already exists, and a team of researchers at Washington University is working toward a nasal vaccine for avian influenza. That team includes Boon and co-author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine, and one of the inventors of the nasal vaccine technology used in this paper.
“Mucosal
vaccines are the future of vaccines for respiratory infections,” Boon said.
“Historically, developing such vaccines has been challenging. There’s still so
much we don’t know about the kind of immune response we need and how to elicit
it. I think we’re going to see a lot of very exciting research in the next few
years that could lead to big improvements in vaccines for respiratory
infections.”
Reference:
“Mucosal immunization with ChAd-SARS-CoV-2-S prevents sequential transmission
of SARS-CoV-2 to unvaccinated hamsters” by Tamarand L. Darling, Houda H.
Harastani, Astha Joshi, Traci L. Bricker, Nadia Soudani, Kuljeet Seehra, Ahmed
O. Hassan, Michael S. Diamond and Adrianus C. M. Boon, 31 July 2024, Science
Advances.
DOI:
10.1126/sciadv.adp1290
The
study was funded by the National Institute of Allergy and Infectious Diseases.
Disclosures:
M.S.D. is a consultant for inbios, vir Biotechnology, Ocugen, topspin
therapeutics, GlaxoSmithKline, Allen & Overy llP, Moderna and immunome. the
Diamond laboratory has received unrelated funding support in sponsored research
agreements from vir Biotechnology, emergent BioSolutions and Moderna. M.S.D.
and A.O.h. are inventors of the chAd-SARS-cov-2 technology, which Washington
University has licensed to Bharat Biotech and Ocugen inc. for commercial
development. the Boon laboratory has received unrelated funding support in
sponsored research agreements from Greenlight Biosciences inc. the Boon
laboratory has received funding support from Abbvie inc. for the commercial
development of SARS-cov-2 mAb and Moderna for unrelated work. All other authors
declare that they have no competing interests.
