Developing mucosal vaccines for respiratory viruses is an important area of research because respiratory viruses typically enter the body through the mucosal surfaces of the respiratory tract, such as the nose, mouth, and throat. Mucosal vaccines work by stimulating an immune response at these sites, which can help prevent infection and reduce transmission of the virus.
Long-lasting vaccines against influenza, coronaviruses, and respiratory syncytial virus (RSV) have proven exceedingly difficult to develop. Researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), explore the challenges and outline approaches to improved vaccines in a new review article published in Cell Host & Microbe. Former NIAID director Anthony S. Fauci, M.D., is one of the authors, along with Jeffery K. Taubenberger, M.D., Ph.D., and David M. Morens, M.D.
Unlike the respiratory viruses that cause measles, mumps, and rubella, for which vaccination or recovery from illness provides decades-long protection from future infection, flu, RSV, SARS-CoV-2, and “common cold” coronaviruses share several characteristics that allow them to cause re-infections. These characteristics include extremely short incubation periods, rapid host-to-host transmission, and replication in the nasal mucosa rather than throughout the body. Non-systemic replication means that these viruses do not elicit the full force of the adaptive immune response, which can take a week or more to mount.
We are excited and invigorated that many investigators…are rethinking, from the ground up, all of our previous assumptions and approaches to preventing important respiratory viral diseases and working to find bold new paths forward.
NIAID authors
A next generation of improved vaccines for mucosa-replicating viruses will require advances in understanding on several fronts, the authors say. For instance, more must be learned about interactions between flu viruses, coronaviruses, and RSV and the components of the immune response that operate largely or exclusively in the upper respiratory system. Over time, these interactions have evolved and led to “immune tolerance,” wherein the human host tolerates transient, limited infections by viruses that are generally non-lethal to avoid the destructive consequences of an all-out immune system attack.
One of the challenges in developing mucosal vaccines for respiratory viruses is delivering the vaccine to the right site in the respiratory tract. Researchers are exploring different delivery methods, such as sprays, inhalers, and intranasal drops, to improve the effectiveness of mucosal vaccines.
When feasible, the authors note that mucosal immunization appears to be an optimal route of vaccination for the viruses of interest. However, significant knowledge gaps must be filled in order to develop useful mucosal vaccines, such as finding ideal vaccine formulations, determining dosage size, frequency, and timing, and developing techniques for overcoming immune tolerance.
The NIAID authors encourage other researchers to “think outside the box” in order to make progress toward vaccines that can provide long-term protection against these viruses with significant public health implications. “We are excited and invigorated that many investigators…are rethinking, from the ground up, all of our previous assumptions and approaches to preventing important respiratory viral diseases and working to find bold new paths forward,” they conclude.
Overall, developing mucosal vaccines for respiratory viruses is an important area of research that has the potential to reduce the spread of respiratory infections and improve public health.
