All successful vaccines against SARS-CoV-2 have used the spike protein as the target and delivered the vaccine by intramuscular injection, typically a shot in the left or right shoulder. The vaccines have proven to be spectacularly effective, protecting against infection, severe disease, and death. However, recent mutations of SARS-CoV-2 have created varients that can cause breakthrough infections at a significant rate. While those who are vaccinated are still protected against severe disease and death, protection against infection does appear to wane after several months. This can allow the virus to continue to spread and impact those who cannot or will not get vaccinated. SARS-CoV-2 infection begins in the nose and the upper respiratory tract. Intramuscular injection does not stimulate strong mucosal immunity in these areas.
An et al. from the University of Texas have developed a single-dose intranasal vaccination system that elicits rapid systemic and mucosal immunity. Importantly, spike-specific IgA responses are present in the nasal compartment and the lung after vaccination and will presumably be better at preventing infection than current vaccines. Inhaled vaccines were difficult to deliver and there was a need for appropriate adjuvants that would stimulate a robust response. (Adjuvants are added to vaccines to enhance the body's immune response to an antigen.) The authors report the creation of adjuvants that stimulate the STING pathway (STINGa) was the key to vaccine effectiveness.
STINGa was formulated in liposome particles by a simple hydration procedure. These nanoSTING particles were stable at refrigerator temperatures. The active vaccine was created by mixing lyophilized spike proteins with nanoSTING and immediately inoculating mice with the mixture. A convenient, foolproof method of preparing the vaccine will have to be developed for this to have widespread use.
The mice vaccinated with nanoSTING had a rapid immune response in 15 days. The response included neutralizing antibodies, B-cells, T-cells, and serum IgA. Especially important, a strong immune response was found in the nasal immune tissue of the mice, suggesting that they would have strong protection against infection with SARS-CoV-2. Unfortunately, the immunized mice were not challenged by infection since they are not an appropriate model for these types of studies. The authors indicate that studies in hamsters or monkeys where viral challenges are possible is the next set of experiments.
There is a long way to go before this hits clinical trials, but it may eventually be a path toward more robust protection against respiratory viruses.