Abstract
Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children < 5 years of age worldwide and repeated infections throughout life leading to serious disease in the elderly and persons with compromised immune, cardiac, and pulmonary systems. The disease burden has made it a high priority for vaccine and antiviral drug development but without success except for immune prophylaxis for certain young infants. Two RSV proteins are associated with protection, F and G, and F is most often pursued for vaccine and antiviral drug development. Several features of the G protein suggest it could also be an important to vaccine or antiviral drug target design. We review features of G that effect biology of infection, the host immune response, and disease associated with infection. Though it is not clear how to fit these together into an integrated picture, it is clear that G mediates cell surface binding and facilitates cellular infection, modulates host responses that affect both immunity and disease, and its CX3C aa motif contributes to many of these effects. These features of G and the ability to block the effects with antibody, suggest G has substantial potential in vaccine and antiviral drug design.
Highlights
Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children < 5 years of age worldwide, causing an estimated 3.4 million hospitalizations, 95,000–150,000 deaths globally, and up to 175,000 hospitalizations in the United States [1,2]
Some of the obstacles to vaccine development include concern that a non-live virus vaccine for young children may predispose to enhanced RSV disease (ERD); an incomplete understanding of protective immunity and disease pathogenesis; immature or altered immune responses in two target populations, young children, and elderly adults; and the cost of clinical vaccine trials
We provide examples of functional features of G that contribute to these effects and note how this supports G’s potential contribution to an RSV vaccine and as a target for anti-viral drug development
Summary
Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children < 5 years of age worldwide, causing an estimated 3.4 million hospitalizations, 95,000–150,000 deaths globally, and up to 175,000 hospitalizations in the United States [1,2]. The first RSV vaccine trial with a formalin-inactivated RSV with alum adjuvant (FI-RSV) led to the concern for enhanced RSV disease (ERD) In this trial, young children who received the vaccine had an unexpected high rate of hospitalization with later RSV infection, and two infected children died [9,10,11,12]. The fact that prior infection and high titers of neutralizing antibodies, including those that are maternally derived, provide some protection from disease, and the effectiveness of immune prophylaxis with a neutralizing F protein monoclonal supports the F protein as important to a vaccine [20,21,22,23,24,25,26]. We provide examples of functional features of G that contribute to these effects and note how this supports G’s potential contribution to an RSV vaccine and as a target for anti-viral drug development
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