Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses

Abstract

Viruses that replicate in the human respiratory mucosa without infecting systemically, including influenza A, SARS-CoV-2, endemic coronaviruses, RSV, and many other "common cold" viruses, cause significant mortality and morbidity and are important public health concerns. Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines. In this review, we examine challenges that have impeded development of effective mucosal respiratory vaccines, emphasizing that all of these viruses replicate extremely rapidly in the surface epithelium and are quickly transmitted to other hosts, within a narrow window of time before adaptive immune responses are fully marshaled. We discuss possible approaches to developing next-generation vaccines against these viruses, in consideration of several variables such as vaccine antigen configuration, dose and adjuventation, route and timing of vaccination, vaccine boosting, adjunctive therapies, and options for public health vaccination polices.

Figure 1

Alveolar damage in fatal COVID-19 lung autopsy samples Multicolor immunofluorescence showing prosurfactant protein C (green) and E-cadherin (red) expression in normal lung tissue (top) and in a COVID-19 lung autopsy case (bottom). Nuclei are stained blue. Normal lung tissue alveolar septa show prominent prosurfactant protein C and E-cadherin expression in lung alveolar type 2 cells and epithelial junctions, respectively, compared to fatal COVID-19 lung tissue, which shows marked loss of alveolar septal prosurfactant protein C and E-cadherin staining and intra-alveolar accumulation of positive-stained epithelial debris. The images demonstrate the extensive damage to the lung observed in a fatal COVID-19 case. New generations of vaccines against respiratory viruses like SARS-CoV-2 and influenza viruses are critically important for preventing pulmonary pathology, serious illness, and death. Images of normal lung and a COVID-19 autopsy case are derived from D’Agnillo F, et al. Sci Transl Med. 2021;13(620):eabj7790. Images courtesy of Dr. Felice D’Agnillo of the US Food and Drug Administration.