Respiratory syncytial virus vaccines

Abstract

Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically distinct RSV groups, A and B; and the history of disease enhancement following administration of a formalin-inactivated vaccine. It is likely that more than one type of vaccine will be needed to prevent RSV LRI in the various populations at risk. Although vector delivery systems, synthetic peptide, and immune-stimulating complex vaccines have been evaluated in animal models, only the purified F protein (PFP) subunit vaccines and live attenuated vaccines have been evaluated in recent clinical trials. PFP-2 appears to be a promising vaccine for the elderly and for RSV-seropositive children with underlying pulmonary disease, whereas live cold-passaged (cp), temperature-sensitive (ts) RSV vaccines (denoted cpts vaccines) would most probably be useful in young infants. The availability of cDNA technology should allow further refinement of existing live attenuated cpts candidate vaccines to produce engineered vaccines that are satisfactorily attenuated, immunogenic, and phenotypically stable.

FIG. 1

Passage history of RSV A2 cpts vaccine candidates. Cell monolayer cultures were used to isolate or cold-passage RSV A2. HEK, human embryonic kidney cells; BEK, bovine embryonic kidney cells; MRC-5, a human diploid lung cell line; Vero, the well-characterized World Health Organization continuous cell line of African green monkey kidney cells; ∗, vaccines which have been evaluated in humans. Courtesy of James E. Crowe, Jr.