info:eu-repo/semantics/article
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease
Fecha
2009-01Registro en:
Delgado, Maria Florencia; Coviello, Silvina Andrea; Monsalvo, Ana Clara; Melendi, Guillermina Amanda; Hernandez, Johanna Zea; et al.; Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease; Nature Publishing Group; Nature Medicine; 15; 1; 1-2009; 34-41
1078-8956
CONICET Digital
CONICET
Autor
Delgado, Maria Florencia
Coviello, Silvina Andrea
Monsalvo, Ana Clara
Melendi, Guillermina Amanda
Hernandez, Johanna Zea
Batalle, Juan Pio
Diaz, Leandro
Trento, Alfonsina
Chang, Herng-Yu
Mitzner, Wayne
Ravetch, Jeffrey
Melero, José A.
Irusta, Pablo M.
Polack, Fernando Pedro
Resumen
Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure. No vaccine has been licensed since that time. A widely accepted hypothesis attributed the vaccine failure to formalin disruption of protective antigens. Here we show that the lack of protection was not due to alterations caused by formalin but instead to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor (TLR) stimulation. This study explains why the inactivated RSV vaccine did not protect the children and consequently led to severe disease, hampering vaccine development for 42 years. It also suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants.