Identification of small-animal and primate models for evaluation of vaccine candidates for human metapneumovirus (hMPV) and implications for hMPV vaccine design

• Published in: Journal of general virology Vol. 85; no. 6; pp. 1655 - 1663
• Main Authors: MacPhail, Mia, Schickli, Jeanne H, Tang, Roderick S, Kaur, Jasmine, Robinson, Christopher, Fouchier, Ron A. M, Osterhaus, Albert D. M. E, Spaete, Richard R, Haller, Aurelia A
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.06.2004; Society for General Microbiology
• Subjects: Animals; Biological and medical sciences; Cercopithecus aethiops; Chlorocebus aethiops; Cricetinae; Ferrets; Fundamental and applied biological sciences. Psychology; Human parainfluenza virus 3; Macaca mulatta; Mesocricetus; Metapneumovirus - immunology; Metapneumovirus - physiology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Models, Animal; Parainfluenza virus; Paramyxovirus; Respiratory syncytial virus; Respiratory System - virology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vero Cells; Viral Vaccines - immunology; Virology; Virus Replication; Canada; USA; Australia; Europe; China, People's Rep., Hong Kong; Design; Human; Prevention; Immunoprophylaxis; Animal model; Vertebrata; Mammalia; Microbiology; Primates; Identification; Vaccine; Virology
• DOI: 10.1099/vir.0.79805-0
• ISSN: 0022-1317

1 MedImmune Vaccines Inc., 297 North Bernardo Avenue, Mountain View, CA 94043, USA 2 Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands Correspondence Aurelia A. Haller aurelia.haller{at}globeimmune.com 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. Present address: GlobeImmune Inc., Aurora, CO 80010, USA.