리서치 하이라이트

Vaccine mystery solved

Nature Medicine

2008년12월15일

In the 1960s, a vaccine against the respiratory syncytial virus (RSV) mysteriously failed to protect children and even made the disease worse. An article in Nature Medicine this week reports data that explain this mystery 40 years later.

RSV?the agent that causes bronchiolitis?is a leading cause of hospitalization in infants worldwide. Over 40 years ago, a formalin-inactivated RSV vaccine was used to immunize children, but it failed to provide protection from the virus and even led to severe disease. A widely accepted explanation for the vaccine’s failure was that formalin disrupted protective antigens?portions of the virus that should have induced the production of protective antibodies.

Fernando Polack and his colleagues now show that the lack of protection was due instead to low antibody affinity for the protective antigens. The maturation of the antibodies was impaired by poor stimulation of Toll-like receptors (TLRs)?immune molecules key for the detection of pathogens. When the authors gave a TLR activator together with a failed vaccine to mice, the mixture provided protection from RSV.

The study explains why the inactivated vaccine did not protect the children, hampering RSV vaccine development for four decades. It also suggests that inactivated RSV vaccines may be rendered effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants.

doi: 10.1038/nm.1894

영어 리서치 하이라이트