NANOBODIES® PROTECT MICE AGAINST HUMAN RESPIRATORY SYNCYTIAL VIRUS INFECTION

SCHEPENS B.; IBAÑEZ L.I.; HULTBERG A.; MELERO J.; VANDEVELDE W.; VERRIPS C.T.; VANLANDSCHOOT P.; SAELENS X.

Brujas, Bélgica

Congreso; 14th International Negative Strand Virus Meeting 2010; 2010

Infection with human Respiratory Syncytial Virus (HRSV) is the leading cause of lower respiratory tract disease in infants and children world wide. HRSV infections do not evoke long-living immune protection and RSV infections recur throughout life, causing also significant morbidity and mortality in elderly and immune compromised individuals. Currently, there is no vaccine for HRSV, nor is there any effective antiviral therapeutic treatment. However prophylactic administration of HRSV neutralizing antibodies can reduce HRSV associated hospitalization. We have developed monovalent and bivalent, cameloid-derived immunoglobulin single variable domains (VHH domains or VHHs), called Nanobodies®, that can neutralize HRSV in vitro when applied in nano- to picomolar range. We evaluated the potency of these Nanobodies® to protect against HRSV infections in conditionally immune suppressed (cyclophosphamide treated) BALB/c mice. We demonstrate that intranasal administration of bivalent Nanobodies® at least up to 48 hours prior to infection strongly reduced HRSV replication in the lungs. Remarkably, protection against HRSV infection by prophylactic administration of bivalent Nanobodies® was observed at doses as low as 0.5 microgram per mouse. In comparison, protection by monovalent Nanobodies® was much less effective. Finally, we demonstrate that also therapeutic administration of bivalent Nanobodies® can efficiently reduce pulmonary HRSV replication. As cameloid Nanobodies® are easy to produce, very stable and easy to format, they represent promising candidates for future clinical development against HRSV infections.