Abstract
A vaccine for respiratory syncytial virus (RSV) has been actively sought for over 60 years due to the health impacts of RSV disease in infants, but currently the only available preventive measure in Canada and elsewhere is limited to passive immunization for high-risk infants and children with a monoclonal antibody. RSV vaccine development has faced many challenges, including vaccine-induced enhancement of RSV disease in infants. Several key developments in the last decade in the fields of cellular immunology and protein structure have led to new products entering late-stage clinical development. As of July 2019, RSV vaccine development is being pursued by 16 organizations in 121 clinical trials. Five technologies dominate the field of RSV vaccine development, four active immunizing agents (live-attenuated, particle-based, subunit-based and vector-based vaccines) and one new passive immunizing agent (monoclonal antibody). Phase 3 clinical trials of vaccine candidates for pregnant women, infants, children and older adults are under way. The next decade will see a dramatic transformation of the RSV prevention landscape.
Highlights
Respiratory syncytial virus (RSV) infection represents a large burden of disease in Canada and worldwide
Vaccinia Ankara (MVA) virus, based on the orthopox virus used as a vaccine against smallpox. This vector is used to express several RSV antigens, including wild-type F, G, N, M2-1, and potentially other proteins. This candidate is in the Phase 2 clinical trials of modified Vaccinia Ankara virus (MVA)-Bavarian Nordic (BN)-RSV in older adults [National Clinical Trial (NCT)02873286] for either a one or two-dose strategy via intramuscular route of administration
In Phase 3 clinical trials in pregnant women, this vaccine did not meet its primary objective but still demonstrated 39% efficacy in reducing RSV-induced lower respiratory tract infection (LRTI) within the first 90 days of life and in reducing hospitalization by 44%, with the most protection seen if the vaccine was delivered before 33 weeks gestation (NCT02624947)
Summary
Respiratory syncytial virus (RSV) infection represents a large burden of disease in Canada and worldwide. Without specific stabilization or modification, the F protein will exist in a spectrum of conformations, which will have different antigenic and neutralization profiles. Without stabilization, this immunogen will settle into a postfusion conformation over time. Severe disease clinically manifests as influenza‐like illnesses and lower respiratory tract infection (LRTI), with bronchiolitis the most common severe presentation in young children. RSV vaccine development has leveraged advances in understanding of T-cell biology and protein structure as well as a better delineation of different populations at risk for RSV. Phase 3 clinical trials that target pediatric, older adult and maternal populations are under way. Target populations and to identify current challenges to developing a vaccine for RSV
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