Researchers exploring the development of mucosal vaccines for respiratory viruses

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NIH experts provide perspective on next-generation methods.

It has been extremely difficult to create vaccines that offer long-lasting protection from influenza, coronaviruses and respiratory syncytial viruses (RSV). In a review article published in cell host & microbe by researchers at the National Institute of Allergy and Infectious Diseases, part of the NIH explores the challenges and outlines approaches for improved vaccines. Anthony S. Fauci M.D. is the former NIAID Director, along with Jeffery Taubenberger M.D. Ph.D. and David M. Morens M.D.

The flu, RSV and SARS-CoV-2 coronaviruses, as well as the “common cold”, share several characteristics which allow them to cause repeated infections. The characteristics include rapid transmission from host to host, a very short incubation period, and the ability to replicate in the nasal mucosa instead of throughout the body. This last feature–non-systemic replication–means these viruses do not stimulate the full force of the adaptive immune response, which typically takes a week or more to mount.

The authors state that in order to develop a next-generation of improved vaccines against mucosa replicating viruses, it will be necessary to make advances on multiple fronts. In particular, it is necessary to learn more about the interactions between influenza viruses, coronaviruses and RSV, as well as the immune components that are primarily or exclusively active in the upper respiratory tract. These interactions have evolved over time and resulted in “immune toleration,” where the human host is able to tolerate transient, non-lethal infections from viruses.

When possible, the authors state that mucosal vaccination is an optimal method of immunizing against viruses of concern. To develop effective mucosal vaccinations, there are still significant knowledge gaps to be filled. These include finding the ideal formulation of vaccines, determining the dosage size, frequency and timing, and developing techniques to overcome immune tolerance.

The NIAID authors encourage fellow researchers to think “outside the box” in order to progress toward vaccines capable of providing durable protection against viruses that have a significant impact on public health. The authors conclude: “We are excited and energized that many investigators…are working to find bold, new ways forward and rethinking all of our previous assumptions and approaches in preventing important respiratory viral disease.”

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