Native RSV (Strain Long) Grade 2

Respiratory syncytial virus (RSV) is a major pathogen that causes devastating respiratory infections in both infants and the elderly. RSV belongs to the Paramyxoviridae family's Pneumovirus genus. Its genome is made up of non-segmented, single-stranded negative-sense RNA that is encased in a number of structural and functional proteins.Viral entry and reproduction depend on these proteins, particularly the fusion protein (F protein) and attachment protein (G protein). They are also important targets for the creation of therapeutic medications and vaccinations. Eleven viral proteins, including three non-structural proteins (NS1, NS2) and numerous structural proteins including nucleoprotein (N), matrix protein (M), fusion protein (F), and glycoprotein (G), are encoded by ten genes in the RSV genome. These proteins have particular functions in viral replication, genome duplication, and host interactions. For example, NS1 and NS2 inhibit the host's interferon response, which allows the virus to evade immune detection, while the N protein binds firmly to RNA to form the viral nucleocapsid and takes part in viral RNA replication. By attaching to cell surface receptors, the G protein mainly mediates the virus's attachment to the host cell, promoting viral adsorption and infection. The F protein is a crucial target in the creation of vaccines because it facilitates the fusion of the viral membrane with the host cell membrane, allowing the virus to enter the cell. The key distinction between RSV's two main antigenic subtypes, A and B, is found in their G proteins. The F protein is highly conserved between subtypes A and B, but the G proteins of the two share only 5% homology. Therefore, the majority of vaccinations and therapeutic antibodies under research target the F protein. The F protein, a class I fusion glycoprotein, combines with the host cell membrane to facilitate the virus's entry into the cell. The F protein changes significantly from a pre-fusion (pre-F) to a post-fusion (post-F) structure during infection. The best antibodies for avoiding infection are thought to be those that are specific to the pre-F conformation. In order to improve vaccine efficacy, numerous novel vaccines are being developed to stabilize this pre-fusion phase.

Figure 1. Structure of RSV (Source: Lambert L, et al., 2014)

RSV is primarily transmitted through airborne droplets, and infants and the elderly are at high risk. Infants are particularly vulnerable to RSV, with the infection often manifesting as bronchiolitis and pneumonia. Globally, approximately one-third of infant's contract RSV within their first year of life, with many cases progressing to severe lower respiratory tract infections, requiring hospitalization. RSV infection is highly recurrent, as it does not induce long-lasting immunity. Thus, while infants may experience severe symptoms during the initial infection, reinfections are common, though usually milder. Treatment for infants and children focuses on symptom management and reducing the risk of complications. Currently, RSV prevention in infants relies on monoclonal antibodies such as palivizumab (Synagis) and nirsevimab (Beyfortus), which neutralize the F protein, preventing the virus from entering host cells and thereby reducing the incidence of infection. Additionally, significant progress has been made in RSV vaccine development. In recent years, vaccines developed by Pfizer and GlaxoSmithKline (RSVPreF and RSVPreF3) have been approved by the U.S. FDA for use in adults over 60 to prevent RSV infection. However, vaccine development for infants and children remains challenging, particularly due to weak immune responses in newborns, safety concerns, and incomplete understanding of the pathogenesis of RSV. Nonetheless, subunit vaccines targeting the pre-F protein and mRNA vaccines are under clinical development, offering hope for effective RSV protection in infants and children in the future. Beyond infants, the elderly and immunocompromised adults are also at high risk for RSV infection. As the global population ages, RSV poses an increasing threat to elderly health. Statistics show that tens of thousands of adults over 65 are hospitalized due to RSV infection each year in the U.S., with some progressing to severe disease, even resulting in death. RSV infection is not limited to the upper respiratory tract; many elderly patients develop lower respiratory complications such as tracheobronchitis and pneumonia, which increase mortality rates. The decline in immune function in older adults makes them more susceptible to RSV infection and prolongs recovery time. Therefore, RSV vaccine development for the elderly has also become a focus of attention.

Figure 2. RSV binding and entry into host cells (Source: Griffiths C, et al., 2017)

The development of RSV vaccines has faced significant hurdles. Early clinical trials were halted due to issues with vaccine-enhanced respiratory disease (ERD), which forced the suspension of many vaccine candidates. However, with a deeper understanding of the structure of the F protein and the virus's immunological mechanisms, researchers have gradually developed new-generation vaccines that can avoid ERD. In particular, improvements in stabilizing the pre-F conformation of the F protein have made the development of effective vaccines possible. Currently, besides protein-based subunit vaccines, nucleic acid vaccines such as mRNA vaccines show great promise. These vaccines express viral proteins directly in host cells, avoiding the complexities of protein structure design and simplifying vaccine production processes.

Respiratory syncytial virus (RSV) strain Long
RSV Long strain
Native RSV Grade 2