Nasal Delivery Produces More Immune Response Than Muscular Injection
Scientists at Washington University School of Medicine in St. Louis have developed a vaccine that targets the SARS-CoV-2 virus, are often given in one dose via the nose and is effective in preventing infection in mice vulnerable to the novel coronavirus. The investigators next plan to test the vaccine in nonhuman primates & humans to ascertain if it’s safe and effective in preventing COVID-19 infection.
The study is out there online within the journal Cell.
Unlike other COVID-19 vaccines in development, this one is delivered via the nose, often the initial site of infection. within the new study, the researchers found that the nasal delivery route created a robust immune reaction throughout the body, but it had been particularly effective within the nose & respiratory tract , preventing the infection from taking hold the body.
“We were happily surprised to ascertain a robust immune reaction within the cells of the inner lining of the nose and upper airway — and a profound protection from infection with this virus,” said senior author Michael S. Diamond, MD, PhD, The Herbert S. Gasser Professor of-medicine & a Professor of molecular microbiology, and of pathology and immunology. “These mice were well shielded from disease. And in a number of the mice, we saw evidence of sterilizing immunity, where there’s no sign of infection whatsoever after the mouse is challenged with the virus.”
To develop the vaccine, the researchers inserted the virus spike protein, which coronavirus uses to invade cells, inside another virus — called an adenovirus — that causes the cold . But the scientists tweaked the adenovirus, rendering it unable to cause illness. 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 new vaccine incorporates two mutations into the spike protein that stabilize it during a specific shape that’s most conducive to forming antibodies against it.
“Adenoviruses are the idea for several investigational vaccines for COVID-19 and other infectious diseases, like Ebola virus & tuberculosis, and that they have good safety and efficacy records, but not much research has been through with nasal delivery of those vaccines,” said co-senior author David T. Curiel, MD, PhD, The Distinguished Professor of Radiation Oncology. “All of the opposite adenovirus vaccines in development for COVID-19 are delivered by injection into the arm or thigh muscle. The nose may be a novel route, so our results are surprising and promising. it is also important that one dose produced such a strong immune reaction . Vaccines that need 2 doses for full protection are less effective because some people, for various reasons, never receive the second dose.”
Although there’s an influenza vaccine called FluMist that’s delivered through the nose, it uses a weakened sort of the live influenza virus and cannot be administered to certain groups, including those whose immune systems are compromised by illnesses like cancer, HIV & diabetes. In contrast, the new COVID-19 intranasal vaccine during this study doesn’t use a live virus capable of replication, presumably making it safer.
The researchers compared this vaccine administered to the mice in 2 ways — within the nose & through muscular injection . While the injection induced an immune reaction that prevented pneumonia, it didn’t prevent infection within the nose and lungs. Such a vaccine might reduce the severity of COVID-19, but it might 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 tract — the nose and lungs — suggesting that vaccinated individuals wouldn’t spread the virus or develop infections elsewhere within the body.
The researchers said the study is promising but cautioned that the vaccine thus far has only been studied in mice.
“We will soon begin a study to check this intranasal vaccine in nonhuman primates with an idea to move into human clinical trials as quickly as we will ,” Diamond said. “We’re optimistic, but this must continue browsing the right evaluation pipelines. In these mouse models, the vaccine is very protective. We’re looking forward to beginning subsequent round of studies & ultimately testing it in people to ascertain if we will induce the sort of protective immunity that we expect not only will prevent infection but also curb pandemic transmission of this virus.”
This work was supported by the National Institutes of Health (NIH), grant and contract numbers 75N93019C00062, R01 AI127828, R01 AI130591, R01 AI149644, R35 HL145242, HHSN272201400018C, HHSN272201200026C, F32 AI138392 and T32 AI007163; the Defense Advanced Scientific Research Agency, grant number HR001117S0019; a Helen Hay Whitney Foundation postdoctoral fellowship; and therefore the Pulmonary Morphology Core at Washington University School of medicine.
Diamond may be a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and on the scientific planning board of Moderna. The Diamond laboratory has received unrelated funding support from Moderna, Vir Biotechnology, & Emergent BioSolutions. Diamond, Curiel, Ahmed Hassan & Igor Dmitriev have filed a disclosure with Washington University for possible development of ChAd-SARS-CoV-2. Michael Holtzman may be a member of the DSMB for AstroZeneca and founding father of NuPeak Therapeutics. The Baric laboratory has received unrelated funding support from Takeda, Pfizer & Eli Lily.