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Evaluating the Potential of Next-Generation Vaccines for Respiratory Viruses


A perspective article discussed the possible approaches that scientists can take in developing a new generation of vaccines to fight against several respiratory viruses.

Several variables, such as route and timing of vaccination and options for public health vaccination policies, need to be considered when developing a new generation of vaccines to combat respiratory viruses, according to a perspective article published in Cell Host & Microbe. The perspective—coauthored by former director of the National Institute of Allergy and Infectious Diseases, Anthony Fauci, MD—brought up considerations and factors that could influence future vaccine development.

The authors believe that the creation of effective vaccines against endemic respiratory viruses is vital, with influenza the direct cause of 12,000 to 52,000 deaths in the United States each year. Vaccine effectiveness against influenze has not improved much in the past 6 decades, and the deficiencies in the vaccines have extended to the COVID-19 vaccines, the most notable deficiency being that the protection does not last very long.

Compared with viruses that are well controlled through vaccines (eg, smallpox, measles, mumps, rubella), these respiratory viruses have shorter incubation periods, replicate in the local mucosal tissue, and don’t encounter the systemic immune system or adaptive immune responses, which leads to reinfection without durable protection. Key challenges exist to creating vaccines that can effectively protect people against respiratory viruses for a longer amount of time.

Mucosal respiratory viruses often have similar signs and symptoms, including a short duration of illness that includes sneezing, a sore throat, cough, and a low or absent fever. These similar symptoms indicate that the viruses likely have similar pathogenic mechanisms. The authors believe that the biggest challenges of creating a vaccine to counter them are that humans have evolved to accept viral tolerance during the time of viral replication and short incubation periods are able to allow for viral spread before the immune system can be activated. Vaccines should both dampen initiation of infection and control infection after inoculation.

Host immune mechanisms need to be taken advantage of as well, as mucosal and systemic immunity don’t fully protect against infection against mucosal respiratory viruses. Trained innate immunity has been found to offer promise for vaccines to boost innate immune responses, but learning about controlling these responses is still an unexplored area of research. Secretory mucosal immunity has been found to be more effective than systemic immunity in this area. Limiting viral spread is also an important consideration other than preventing the initial infection.

Knowledge and understanding of immune correlates of protection against respiratory viruses is low, which means that identifying those strong immunologic correlates of protection is vital in developing next-generation vaccines. The authors claim that immune correlate studies need to be a research priority. Consensus for the desired levels of protection, whether it be preventing the infection entirely or limiting viral replication, is needed to attain the desired effects.

One of the other challenges is to have public health considerations contribute to shaping a vaccine design, schedule, role of boosting, and frequency of vaccination. Recipes and schedules for the vaccine will need to be refined to get the best results for durable protective immunity. Doing more research on the effectiveness of repeated antigenic exposures in immunization could help inform public health policies on vaccination.

The authors concluded that durable protective vaccines have been elusive to develop thus far and the challenges are complex. The researchers said that thinking outside the box and working from the ground up can help inspire new paths in developing these vaccines in the future.


Morens DM, Taubenberger JK, Fauci AS. Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses. Cell Host Microbe. Published online January 11, 2023. doi:10.1016/j.chom.2022.11.016

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