Vaccine Takes a Toll

Abstract

VIROLOGY Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants, and early exposure to the virus is thought to confer an increased risk of wheezing and asthma later in life. Efforts to develop a protective vaccine suffered a major setback in the 1960s when a formalin-inactivated vaccine against RSV (FIRSV) not only failed to protect against viral infection, but severely exacerbated lung disease in vaccinated infants and children, many of whom required hospitalization. Forty years later, Delgado et al. offer a fresh perspective on why the FIRSV vaccine may have failed. Studying the immune responses in mice treated with wild-type RSV or with either of two inactivated vaccines [FIRSV or a vaccine inactivated by ultraviolet light (UVRSV)], they found that both inactivated vaccines elicited short-lived antibodies that were nonprotective. Further experiments with UVRSV revealed that these antibodies had a low affinity for crucial viral antigens and that this was due to deficient activation of Toll-like receptor (TLR) signaling in B cells. Mice that had been treated with both UVRSV and TLR agonists and then infected with RSV had lower levels of virus and milder lung disease than mice treated with the vaccine alone. These results cast doubt on an earlier hypothesis attributing the vaccine failure to formalin-mediated disruption of viral antigens, and they raise the possibility that agents stimulating the TLR pathway may enhance the efficacy of future candidate vaccines. — PAK Nat. Med. 10.1038/nm.1894 (2008).