Delivery of ALX-0171 by inhalation greatly reduces respiratory syncytial virus disease in newborn lambs.
MAbs
; 10(5): 778-795, 2018 07.
Article
en En
| MEDLINE
| ID: mdl-29733750
ABSTRACT
Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory disease in infants and young children worldwide. Currently, treatment is supportive and no vaccines are available. The use of newborn lambs to model hRSV infection in human infants may provide a valuable tool to assess safety and efficacy of new antiviral drugs and vaccines. ALX-0171 is a trivalent Nanobody targeting the hRSV fusion (F) protein and its therapeutic potential was evaluated in newborn lambs infected with a human strain of RSV followed by daily ALX-0171 nebulization for 3 or 5 consecutive days. Colostrum-deprived newborn lambs were infected with hRSV-M37 before being treated by daily nebulization with either ALX-0171 or placebo. Two different treatment regimens were examined day 1-5 or day 3-5 post-infection. Lambs were monitored daily for general well-being and clinical parameters. Respiratory tissues and bronchoalveolar lavage fluid were collected at day 6 post-inoculation for the quantification of viral lesions, lung viral titers, viral antigen and lung histopathology. Administration by inhalation of ALX-0171 was well-tolerated in these hRSV-infected newborn lambs. Robust antiviral effects and positive effects on hRSV-induced lung lesions and reduction in symptoms of illness were noted. These effects were still apparent when treatment start was delayed and coincided with peak viral loads (day 3 post-infection) and at a time point when signs of RSV disease were apparent. The latter design is expected to have high translational value for planned clinical trials. These results are indicative of the therapeutic potential of ALX-0171 in infants.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades de las Ovejas
/
Virus Sincitial Respiratorio Humano
/
Infecciones por Virus Sincitial Respiratorio
/
Modelos Animales de Enfermedad
/
Anticuerpos de Dominio Único
Tipo de estudio:
Clinical_trials
Límite:
Animals
/
Humans
/
Infant
Idioma:
En
Revista:
MAbs
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos