Current State and Challenges in Developing Respiratory Syncytial Virus Vaccines

Abstract

Respiratory syncytial virus (RSV) is the main cause of acute respiratory tract infections in infants and it also induces significant disease in the elderly. The clinical course may be severe, especially in high-risk populations (infants and elderly), with a large number of deaths in developing countries and of intensive care hospitalizations worldwide. To date, prevention strategies against RSV infection is based on hygienic measures and passive immunization with humanized monoclonal antibodies, limited to selected high-risk children due to their high costs. The development of a safe and effective vaccine is a global health need and an important objective of research in this field. A growing number of RSV vaccine candidates in different formats (particle-based vaccines, vector-based vaccines, subunit vaccines and live-attenuated vaccines) are being developed and are now at different stages, many of them already being in the clinical stage. While waiting for commercially available safe and effective vaccines, immune prophylaxis in selected groups of high-risk populations is still mandatory. This review summarizes the state-of-the-art of the RSV vaccine research and its implications for clinical practice, focusing on the characteristics of the vaccines that reached the clinical stage of development.

Respiratory Syncytial Virus (RSV) G Protein Vaccines With Central Conserved Domain Mutations Induce CX3C-CX3CR1 Blocking Antibodies

“…Given the need for a safe and efficacious RSV vaccine, several studies are currently evaluating various vaccine candidates using different platforms, i.e., codon deoptimized live attenuated, subunit, particle, and vector-based, using different RSV antigens including F protein, G protein, and/or M protein [ 28 , 71 , 72 , 73 ]. While the F protein is the RSV vaccine antigen often evaluated, the G protein should also be considered as it can induce neutralizing activities and block CX3C-CX3CR1 interaction [ 42 , 47 , 48 , 74 , 75 ].…”

A Recombinant BCG Vaccine Is Safe and Immunogenic in Neonatal Calves and Reduces the Clinical Disease Caused by the Respiratory Syncytial Virus

“…The only prophylactic tool to prevent severe infection is Palivizumab, a humanized monoclonal antibody that is used only in high-risk infants due to its high cost ( 58 , 59 ). While several vaccine strategies are under development and clinical testing for either pregnant women, infants, and the elderly ( 58 , 60 ), the development of efficacious vaccines targeting specific age groups faces different challenges at both pre-clinical and clinical levels. RSV-associated morbidity and mortality are higher in infants under one-year-old in low-income countries; thus children remain a critical target population to implement therapeutic and preventive measures ( 57 , 61 ).…”

Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?

“…Prevention plays an essential role in reducing the burden of RSV disease in children and avoiding inappropriate therapies, including antibiotics. Although many vaccine candidates have been in clinical evaluation in the last few decades, none, to date, has reached licensing [ 28 ]. Therefore, while waiting for an effective vaccine, passive immune prophylaxis in children should be mandatory.…”