Vaccines that provide long-lasting protection against influenza, coronaviruses and respiratory syncytial virus (RSV) have proven exceptionally difficult to develop. In a new review article by Cell host and microbe, researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, explore challenges and outline approaches to improving vaccines. Anthony S. Fauci, MD, former director of NIAID, is an author with Jeffery K. Taubenberger, MD, Ph.D., and David M. Morens, MD
Unlike the respiratory viruses that cause measles, mumps and rubella – for which vaccination or cure of a disease offers decades of protection against future infection – the coronaviruses of influenza, RSV, SARS-CoV -2 and the “cold” share several characteristics that can cause repeated reinfections. These include very short incubation periods, rapid host-to-host transmission, and replication in the nasal mucosa rather than throughout the body. This last characteristic – non-systemic replication – means that these viruses do not stimulate the full force of the adaptive immune response, which generally takes a week or more to develop.
According to the authors, a next generation of improved vaccines against mucosal-replicating viruses will require advances in understanding on several fronts. For example, more needs to be known about the interactions between influenza 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 evolved and led to “immune tolerance”, in which the human host tolerates transient and limited infections by viruses that are generally non-lethal to avoid the destructive consequences of an all-out attack of the virus. immune system.
The authors note that mucosal immunization appears to be an optimal vaccination route for the viruses of interest, when possible. However, to develop useful mucosal vaccines, significant knowledge gaps need to be filled, including finding ideal vaccine formulations; determining the size, frequency and timing of the dosage; and developing techniques to overcome immune tolerance.
The NIAID authors urge their fellow researchers to “think outside the box” to make progress toward vaccines capable of achieving long-lasting protection against these viruses with far-reaching public health impact. They conclude, “We are excited and invigorated that many researchers are…rethinking, from the ground up, all of our past assumptions and approaches to preventing important respiratory viral diseases and working to find bold new paths.
