Vaccines for Respiratory Viruses-COVID and Beyond

Abstract

The COVID-19 (coronavirus disease 2019) pandemic had an extensive impact on global morbidity and mortality. Several other common respiratory viruses, such as the influenza virus and respiratory syncytial virus (RSV), are endemic or epidemic agents causing acute respiratory infections that are easily transmissible and pose a significant threat to communities due to efficient person-to-person transmission. These viruses can undergo antigenic variation through genetic mutations, resulting in the emergence of novel strains or variants, thereby diminishing the effectiveness of current vaccines, and necessitating ongoing monitoring and adjustment of vaccine antigens. As the virus-specific immunity is maintained only for several weeks or months after the infection, there is an emergent need to develop effective and durable vaccines. Additionally, specific populations, such as elderly or immunocompromised individuals, may exhibit reduced immune responses to respiratory viruses, posing significant challenges to develop vaccines that elicit durable and potent immunity. We present a comprehensive review of the molecular mechanisms underlying the pathogenesis and virulence of common respiratory viruses, such as RSV, influenza virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss several vaccine approaches that are under development. A thorough understanding of the current strategies and the challenges encountered during the vaccine development process can lead to the advancement of effective next-generation vaccines.

Keywords: SARS-CoV-2; acute respiratory infections; influenza virus; respiratory syncytial virus; vaccine development.

Figure 1

Viral entry and replication mechanisms of common respiratory viruses—(A) influenza viruses (B), respiratory syncytial virus, and (C) SARS-CoV-2.

Figure 2

Immune and cellular responses to respiratory viruses—activated RIG-I (retinoic acid-inducible gene I), a pattern recognition receptor in the cytosol forms a secondary structure with the viral RNA and interacts with the adaptor mitochondrial antiviral-signaling protein (MAVS). Immune cells, including macrophages, identify the virus and produce cytokines. The activation of downstream signaling pathways and transcription factors lead to the induction of innate immune responses via the production of inflammatory cytokines. Cytokines attract more immune cells, which in turn cause them to release additional cytokines, creating an inflammation loop that damages the lung cells through the formation of fibrin. Progression to severe damage results from weakened blood vessels, allowing fluid to seep in and fill the lung cavities, leading to respiratory failure. NF-κB: Nuclear factor kappa B; TLR: Toll-like receptor; IRFs: interferon regulatory factors; TNF-α: tumor necrosis factor-alpha; ILs: interleukins.

Figure 3

Types of vaccines for respiratory viruses—different kinds of vaccines that were considered or are under development to combat respiratory viruses are illustrated. Their respective advantages (in blue) and disadvantages (in red) are also listed.

Figure 4

Advantages of the inhalation vaccine platform—the inhalation route generates a mucosal (IgA) response and robust humoral immune response (IgG), thus generating higher titers of neutralizing antibodies. The secretory IgA in the upper respiratory tract is especially helpful in conferring protection, reducing infection burden, and preventing transmission.