Respiratory viruses continue to be a major cause of mortality and pose a significant risk to human health worldwide, especially in children under 5, older adults, and residents of low- and middle-income countries (LMICs). RSV, influenza virus, human metapneumovirus (hMPV), and coronaviruses are among the respiratory viruses that cause serious disease and high death rates worldwide.(p1) Controlling viruses with vaccines or antiviral drugs poses challenges because of their genetic structure. For vaccines to be effective, they must elicit a neutralizing response against highly conserved epitopes, yet few have proven successful.(p2) Despite decades of scientific research on infectious diseases, pandemics persist, leading to significant mortality. Recent studies indicate significant changes in the epidemiology and traditional disease patterns of respiratory viruses post coronavirus 2019 (COVID-19), necessitating preparedness studies.(p3),(p4),(p5) RSV is one of the primary causes of respiratory infections worldwide, affecting babies under the age of 5 and resulting in 3.6 million hospitalizations and 100 000 deaths each year. Approximately half of all RSV fatalities in children occur in newborns under 6-months old. Most (97%) of pediatric RSV deaths occur in LMICs with inadequate access to supportive medical treatment.(p6) The global estimates of adult RSV illness include ∼3.36 million hospitalizations and 14 000 deaths per year. This virus is particularly pathogenic to humans, able to cause a wide range of respiratory diseases, from mild upper respiratory tract infections (URTI) to severe lower respiratory tract infections (LRTI), which can be fatal.(p7) Research shows that natural infection confers only limited immunity, leading to reinfections.(p8),(p9) In addition, currently available antibodies, although highly effective for prophylaxis, face considerable challenges in a therapeutic setting.

To address these issues, researchers have been exploring single-domain antibodies [Variable domain of Heavy chain of Heavy-chain antibody (VHH), nanobodies, and immunoglobulin domain antibodies (IgDAbs)], which have many advantages over conventional full-length antibodies, including small size, ease of production, and high thermal stability, allowing alternative routes of administration, such as pulmonary delivery by nebulization.(p10) These VHHs can also be engineered with polyvalent and polyspecific formats, significantly increasing their neutralization efficiency.(p11) In this review, we provide a brief overview of the different therapeutics available for RSV and explore the development of nanobodies, in particular PolyBodies, for treating complex viral infections, such as RSV.