The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893-2014.
Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer's study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research.
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Diagnostic Medicine and Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, USA.
A Sally
AS
Davis
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: taubenbergerj@niaid.nih.gov.
Jeffery K
JK
Taubenberger
Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Mike
M
Bray
D032761:Animal Experimentation / Q000266:history; D000818:Animals; D000835:Animals, Wild; D000998:Antiviral Agents / Q000494:pharmacology; D001717:Birds; D049672:History, 19th Century; D049674:History, 21st Century; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000266:history; D005585:Influenza in Birds / Q000266:history / Q000276:immunology / Q000821:virology; D007251:Influenza, Human / Q000266:history / Q000276:immunology / Q000821:virology; D064887:Observational Studies as Topic; D009976:Orthomyxoviridae Infections / Q000266:history / Q000276:immunology / Q000821:virology; D011323:Primates; D014779:Virus Replication
D000998:Antiviral Agents; D007252:Influenza Vaccines
Coinfection; Experimental infection; Influenza A virus; Nonhuman primate; Pathogenesis; Pneumonia