The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893–2014

Abstract

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.

Non-human primate orthologues of TMPRSS2 cleave and activate the influenza virus hemagglutinin

“…The experimental infection of macaques with FLUAV results in viral spread and influenza symptoms, which are usually not as pronounced as those observed in human influenza patients [29,30]. Nevertheless, infection of macaques with highly pathogenic FLUAV, the pandemic H1N1 virus of 1918 and H5N1 avian influenza viruses, induces severe disease and the macaque model has been successfully used for vaccine-, treatment-and pathogenesis-studies [31][32][33]. Based on these studies, it has been suggested that the macaque model mirrors human physiology, development of pneumonia as well as cytokine and chemokine responses more closely than other animal models (mice, ferrets) [34].…”

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

“…Influenza viruses cause recurrent seasonal epidemics or pandemics of respiratory infection that lead to 3 million to 5 million cases of severe illness and 250,000 to 500,000 deaths worldwide every year 1,2 . Especially in infants, young children, pregnant women, the elderly, and patients with weakened immune systems, influenza is likely to cause serious complications; therefore, the World Health Organization (WHO) has identified influenza as a major public health problem 3,4 .…”

Correlation between Virus Replication and Antibody Responses in Macaques following Infection with Pandemic Influenza A Virus

“…onhuman primates (NHP) play an important role as animal models for influenza virus research (1,2). Novel candidate influenza vaccines are commonly tested for safety and efficacy in mice and ferrets and/or macaques before they are evaluated for immunogenicity in humans (2,3).…”

“…Novel candidate influenza vaccines are commonly tested for safety and efficacy in mice and ferrets and/or macaques before they are evaluated for immunogenicity in humans (2,3). However, whereas for mice and ferrets dose-finding studies have been described and implemented for testing of vaccines and antiviral agents (4)(5)(6)(7)(8)(9)(10)(11), for macaques usually a standard challenge dose is used, typically in the range between 10 6 and 10 7 50% tissue culture infective doses (TCID 50 ) (12)(13)(14)(15).…”