COVID-19 vaccination continues to be a topic of intense research, even if it lacks the urgency experienced at the height of the pandemic. One area of focus is the development of mucosal vaccines that can be administered through the nose. These nasal vaccines are inexpensive to produce, easy to store and transport, and useful in places with limited access to trained medical staff.
Now, scientists have developed a live attenuated SARS-CoV-2 vaccine for the nose that shows promise by targeting the mucous membranes of the nose, mouth, throat, and lungs and confers better immunity than vaccines injected into muscle.
This work is published in Nature Microbiology in the paper, “Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters.”
In the fall of last year, two nasal COVID-19 vaccination formulations were approved for use in India and China though these have not yet applied for approval in Europe. These contain modified adenoviruses that are self-attenuating.
The benefits of a nasal vaccine go far beyond being a needleless option. When a vaccine is injected, it infers immunity primarily in the blood and throughout the entire body. In this case, the immune system only detects and combats coronaviruses relatively late in an infection, as they enter the body via the mucous membranes of the upper respiratory tract. “It is here, therefore, that we need local immunity if we want to intercept a respiratory virus early on,” explained Jakob Trimpert, PhD, a research group leader at the Institute of Virology at Freie Universität Berlin.
Scientists tested the efficacy of the newly developed intranasal COVID-19 vaccine on hamster models. They compared “immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters.”
They found that after two doses of the vaccine, the virus could no longer replicate in the model organism. “We witnessed strong activation of the immunological memory, and the mucous membranes were very well protected by the high concentration of antibodies,” Trimpert explained. The vaccine could therefore also significantly reduce the transmissibility of the virus.
In addition, the scientists compared the efficacy of the live attenuated vaccine with that of vaccines injected into the muscle. To do so, they vaccinated the hamsters either twice with the live vaccine, once with the mRNA and once with the live vaccine, or twice with an mRNA or adenovirus-based vaccine. Then, after the hamsters were infected with SARS-CoV-2, they used tissue samples from the nasal mucosa and lungs to see how strongly the virus was still able to attack the mucosal cells. They also determined the extent of the inflammatory response using single-cell sequencing.
The live attenuated vaccine performed better than other vaccines. The best protection against SARS-CoV-2 was provided by double nasal vaccination, followed by the combination of a muscular injection of the mRNA vaccine and the subsequent nasal administration of the live attenuated vaccine.
The next step is safety testing: The researchers are collaborating with RocketVax, a Swiss start-up based in Basel for a Phase I clinical trial in humans.