A vaccination under the skin and a booster in the nose are intended to improve the effectiveness of Covid-19 vaccinations and, if possible, prevent infections with SARS-CoV-2. Scientists at the Medical University of Vienna are also working on such a concept. There are good results from animal models.
The working group from the Center for Pathophysiology, Infectiology and Immunology (Head: Ursula Wiedermann-Schmidt) with first author Joshua Tobias recently published the principle of an improved Covid-19 vaccination in the journal “Vaccines” (https://doi.org/10.3390/vaccines12070795) including their own work with such a strategy. “The development of systemic Covid-19 vaccines (vaccines that are injected; note) has brought about a significant reduction in the severity of the disease, the number of hospital admissions and mortality, thus leading to the containment of the pandemic. Nevertheless, the vaccines have not been able to stop the spread of the virus (SARS-CoV-2; note) because they only generate limited mucosal immunity (in the mucous membranes; note),” the scientists wrote.
SARS-CoV-2 will remain
But SARS-CoV-2 is here to stay. Vaccines or vaccination strategies that stop the transmission of the virus are urgently needed. The scientists: “The upper respiratory tract and the nasal cavity are the primary entry points through which infection with SARS-CoV-2 occurs. Therefore, vaccination via the mucous membrane or nasally would be urgently necessary in order to prevent an immune reaction in the mucosa (mucous membrane; note) and further transmission of the virus.”
According to the World Health Organization (WHO), the Covid-19 vaccination has saved the lives of more than 1.4 million people (25,000 in Austria) in Europe by March 2023, but the continued high transmission rate, including the problem of post-Covid syndrome, represents an ongoing challenge. The Viennese scientists are therefore presenting the status and future prospects for a new strategy: First, an initial vaccination could be given with an injectable vaccine to trigger a systemic immune reaction. This primarily leads to the formation of IgG antibodies, which circulate in the blood and from there also reach the mucous membranes to a certain extent. This also stimulates the formation of B memory cells.
This could then be followed by a booster vaccination with a nasal vaccine. Although this would also produce antibodies circulating in the blood, it would also lead to high concentrations of IgA antibodies (and also IgG antibodies) in the mucous membranes of the SARS-CoV-2 entry point. The vaccination should therefore prevent the viruses from entering the organism in the first place.
For example, the scientists list more than a dozen nasal Covid-19 vaccines being developed in the UK, India, China and Russia (clinical trials). Some of them have already been approved in China, India and Russia.
Preclinical studies and animal models also in Vienna
There are also preclinical studies on the subject in Vienna, including animal models. Using three monoclonal antibodies (sotrovimab, tixagevimab and cilgavimab) that have been used to treat Covid-19, the scientists have identified a peptide (protein fragment) of the spike protein of SARS-CoV-2 that should be particularly suitable as an antigen in a vaccine. As a vaccine, it is intended to stimulate B lymphocytes to produce antibodies. To improve effectiveness, the antigen was bound to a carrier protein (harmless diphtheria toxoid). An adjuvant (montanide) is also used.
Tobias and the team of scientists tested this principle with the vaccine based on the so-called mimotope platform on laboratory mice. Some of them received the vaccine as a nasal vaccine, some as an injection under the skin (with adjuvant), the third group of mice received the vaccine first as an injection (priming) and then also nasally (booster). The main result: With the combination vaccination, a particularly good immune reaction (IgA and IgG antibodies as well as T-cell response) was registered both in the blood and in the mucous membranes (mucosa).
Regardless of whether this project itself leads to a widely applicable Covid-19 vaccine or not, the Viennese scientists expect one thing with some certainty: “It is not unlikely that in the coming years a growing number of mucosal vaccines against SARS-CoV-2 will be approved for use worldwide. It is possible that all Covid-19 vaccines will even become mucosal vaccines.” That would be a real revolution in vaccinology.
