Immune Responses to Respiratory Syncytial Virus Vaccines: Advances and Challenges

Abstract

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory infections, particularly in children and the elderly. This virus primarily infects ciliated epithelial cells and activates alveolar macrophages and dendritic cells, triggering an innate antiviral response that releases pro-inflammatory cytokines. However, immunity generated by infection is limited, often leading to reinfection throughout life. This review focuses on the immune response elicited by newly developed and approved vaccines against RSV. A comprehensive search of clinical studies on RSV vaccine candidates conducted between 2013 and 2024 was performed. There are three primary target groups for RSV vaccines: pediatric populations, infants through maternal immunization, and the elderly. Different vaccine approaches address these groups, including subunit, live attenuated or chimeric, vector-based, and mRNA vaccines. To date, subunit RSV vaccines and the mRNA vaccine have been approved using the pre-fusion conformation of the F protein, which has been shown to induce strong immune responses. Nevertheless, several other vaccine candidates face challenges, such as modest increases in antibody production, highlighting the need for further research. Despite the success of the approved vaccines for adults older than 60 years and pregnant women, there remains a critical need for vaccines that can protect children older than six months, who are still highly vulnerable to RSV infections.

Keywords: Respiratory Syncytial Virus; immune response; vaccine.

Figure 1

RSV vaccine types in clinical trials and approved for use. There are different RSV vaccine types: subunit vaccines, recombinant vector vaccines, live attenuated vaccines, and mRNA vaccines. Three RSV proteins, F, G, and SH, were tested in the subunit vaccine approach. The F protein-based vaccines used two different F protein conformations, post-fusion and pre-fusion. The RSV vaccines approved for use in the elderly and pregnant are subunit and mRNA vaccines based on the pre-fusion conformation.