Abstract
Severe respiratory viral infections, such as influenza, metapneumovirus (HMPV), respiratory syncytial virus (RSV), rhinovirus (RV), and coronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cause significant mortality and morbidity worldwide. These viruses have been identified as important causative agents of acute respiratory disease in infants, the elderly, and immunocompromised individuals. Clinical signs of infection range from mild upper respiratory illness to more serious lower respiratory illness, including bronchiolitis and pneumonia. Additionally, these illnesses can have long-lasting impact on patient health well beyond resolution of the viral infection. Aside from influenza, there are currently no licensed vaccines against these viruses. However, several research groups have tested various vaccine candidates, including those that utilize attenuated virus, virus-like particles (VLPs), protein subunits, and nanoparticles, as well as recent RNA vaccines, with several of these approaches showing promise. Historically, vaccine candidates have advanced, dependent upon the ability to activate the humoral immune response, specifically leading to strong B cell responses and neutralizing antibody production. More recently, it has been recognized that the cellular immune response is also critical in proper resolution of viral infection and protection against detrimental immunopathology associated with severe disease and therefore, must also be considered when analyzing the efficacy and safety of vaccine candidates. These candidates would ideally result in robust CD4+ and CD8+ T cell responses as well as high-affinity neutralizing antibody. This review will aim to summarize established and new approaches that are being examined to harness the cellular immune response during respiratory viral vaccination.
Highlights
Respiratory infections are responsible for significant healthcare burden throughout the world largely due to the development of lower respiratory tract infections (LRTIs)
Evaluation of Adenoviral vector (AdV) vaccines for respiratory syncytial virus (RSV) and influenza has been ongoing for many years and has garnered success but have not yet been approved for human use
An RSV vaccine candidate utilizing the human adenovirus serotypes 26 and 35 encoding the F fusion protein of RSV was tested in mice and cotton rats and indicated high neutralizing antibody levels and F-specific IFN-γ-producing
Summary
Respiratory infections are responsible for significant healthcare burden throughout the world largely due to the development of lower respiratory tract infections (LRTIs). Vaccines 2020, 8, 783 are at high risk of developing LRTIs, making respiratory viral infections a significant cause of morbidity and mortality in these individuals [4,5]. In the case of early-life RSV, males are hospitalized at an approximately a 2:1 ratio compared to females due to lower respiratory tract diseases, such as bronchiolitis and pneumonia [6]. We will discuss the immune responses to respiratory viruses and how the cellular immune response may be harnessed in order to produce more promising vaccine candidates for viruses that have consistently been difficult to target Utilizing these novel strategies will be crucial for developing these prophylactic treatments to protect against initial viral disease as well as protection from long-term consequences
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