Identification of small-animal and primate models for evaluation of vaccine candidates for human metapneumovirus (hMPV) and implications for hMPV vaccine design.
Human metapneumovirus (hMPV), a recently identified paramyxovirus, is the causative agent of respiratory tract disease in young children. Epidemiological studies have established the presence of hMPV in retrospective as well as current clinical samples in Europe, USA, Canada, Hong Kong and Australia. The hMPV disease incidence rate varied from 7 to 12 %. This rate of disease attack places hMPV in severity between respiratory syncytial virus and human parainfluenza virus type 3, two common respiratory pathogens of young children, the elderly and immunosuppressed individuals. To evaluate the effectiveness and safety of future hMPV antiviral drugs, therapeutic and prophylactic monoclonal antibodies (mAbs), and vaccine candidates, it was necessary to identify small-animal and primate models that efficiently supported hMPV replication in the respiratory tract and produced neutralizing serum antibodies, commonly a clinical correlate of protection in humans. In this study, various rodents (mice, cotton rats, hamsters and ferrets) and two primate species, rhesus macaques and African green monkeys (AGMs), were evaluated for hMPV replication in the respiratory tract. The results showed that hamsters, ferrets and AGMs supported hMPV replication efficiently and produced high levels of hMPV-neutralizing antibody titres. Hamsters vaccinated with subgroup A hMPV were protected from challenge with subgroup A or subgroup B hMPV, which has implications for hMPV vaccine design. Although these animal models do not mimic human hMPV disease signs, they will nevertheless be invaluable for the future evaluation of hMPV antivirals, mAbs and vaccines.
MacPhail
Mia
M
MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
Schickli
Jeanne H
JH
MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
Tang
Roderick S
RS
MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
Kaur
Jasmine
J
MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
Robinson
Christopher
C
MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
Fouchier
Ron A M
RAM
Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
Osterhaus
Albert D M E
ADME
Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
Spaete
Richard R
RR
MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
Haller
Aurelia A
AA
MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA.
D000818:Animals; D002522:Chlorocebus aethiops; D006224:Cricetinae; D005289:Ferrets; D008253:Macaca mulatta; D008647:Mesocricetus; D029121:Metapneumovirus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D012137:Respiratory System / Q000821:virology; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
D014765:Viral Vaccines