Experimental Sars Cov-2 Nasal Vaccine protect respiratory tracts
Aug 27, 2020 by News Staff Sci-News.com
A single-dose intranasal vaccine called ChAd-SARS-CoV-2-S prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts of mice, according to a paper published in the journal Cell. The study authors now plan to test the vaccine in non-human primates and humans to see if it is safe and effective in preventing the infection.
Immunization with ChAd-SARS-CoV-2-S induces both neutralizing antibody and antigen-specific CD8+ T cell responses. While a single intramuscular immunization of ChAd-SARS-CoV-2-S confers protection against SARS-CoV-2 infection and inflammation in the lungs, intranasal delivery of the vaccine induces mucosal immunity, provides superior protection, and possibly promotes sterilizing immunity, at least in mice that transiently or stably express the hACE2 receptor. Image credit: Hassan et al, doi: 10.1016/j.cell.2020.08.026.
“We were happily surprised to see a strong immune response in the cells of the inner lining of the nose and upper airway — and a profound protection from infection with this virus,” said Professor Michael Diamond, a researcher at Washington University School of Medicine in St. Louis and corresponding co-author of the study.
“These mice were well protected from disease. And in some of the mice, we saw evidence of sterilizing immunity, where there is no sign of infection whatsoever after the mouse is challenged with the virus.”
To develop the ChAd-SARS-CoV-2-S vaccine, Professor Diamond and colleagues inserted SARS-CoV-2’s spike protein, which coronavirus uses to invade cells, inside another virus — a genetically engineered chimpanzee adenovirus — that causes mild cold-like symptoms in apes but does not normally infect humans.
“Adenoviruses are the basis for many investigational vaccines for COVID-19 and other infectious diseases, such as Ebola virus and tuberculosis, and they have good safety and efficacy records, but not much research has been done with nasal delivery of these vaccines,” said corresponding co-author Professor David Curiel, also from Washington University School of Medicine in St. Louis.
The harmless adenovirus carries the spike protein into the nose, enabling the body to mount an immune defense against the SARS-CoV-2 virus without becoming sick.
In another innovation beyond nasal delivery, the ChAd-SARS-CoV-2-S vaccine incorporates two mutations into the spike protein that stabilize it in a specific shape that is most conducive to forming antibodies against it.
“All of the other adenovirus vaccines in development for COVID-19 are delivered by injection into the arm or thigh muscle,” Professor Curiel said.
“The nose is a novel route, so our results are surprising and promising.”
“It’s also important that a single dose produced such a robust immune response. Vaccines that require two doses for full protection are less effective because some people, for various reasons, never receive the second dose.”
The researchers compared the ChAd-SARS-CoV-2-S vaccine administered to the mice in two ways — in the nose and through intramuscular injection.
While the injection induced an immune response that prevented pneumonia, it did not prevent infection in the nose and lungs.
Such a vaccine might reduce the severity of COVID-19, but it would not totally block infection or prevent infected individuals from spreading the virus.
In contrast, the nasal delivery route prevented infection in both the upper and lower respiratory tract — the nose and lungs — suggesting that vaccinated individuals would not spread the virus or develop infections elsewhere in the body.
“We will soon begin a study to test this intranasal vaccine in nonhuman primates with a plan to move into human clinical trials as quickly as we can,” Professor Diamond said.
“We’re optimistic, but this needs to continue going through the proper evaluation pipelines.”
“In these mouse models, the vaccine is highly protective. We’re looking forward to beginning the next round of studies and ultimately testing it in people to see if we can induce the type of protective immunity that we think not only will prevent infection but also curb pandemic transmission of this virus.”
A.O. Hassan et al. 2020. A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell, in press; doi: 10.1016/j.cell.2020.08.026
This article is based on text provided by Washington University School of Medicine in St. Louis.