Nonhuman Primate Models of Respiratory Disease: Past, Present, and Future

Abstract

The respiratory system consists of an integrated network of organs and structures that primarily function for gas exchange. In mammals, oxygen and carbon dioxide are transmitted through a complex respiratory tract, consisting of the nasal passages, pharynx, larynx, and lung. Exposure to ambient air throughout the lifespan imposes vulnerability of the respiratory system to environmental challenges that can contribute toward development of disease. The importance of the respiratory system to human health is supported by statistics from the Centers for Disease Control and Prevention; in 2015, chronic lower respiratory diseases were the third leading cause of death in the United States. In light of the significant mortality associated with respiratory conditions that afflict all ages of the human population, this review will focus on basic and preclinical research conducted in nonhuman primate models of respiratory disease. In comparison with other laboratory animals, the nonhuman primate lung most closely resembles the human lung in structure, physiology, and mucosal immune mechanisms. Studies defining the influence of inhaled microbes, pollutants, or allergens on the nonhuman primate lung have provided insight on disease pathogenesis, with the potential for elucidation of molecular targets leading to new treatment modalities. Vaccine trials in nonhuman primates have been crucial for confirmation of safety and protective efficacy against infectious diseases of the lung in a laboratory animal model that recapitulates pathology observed in humans. In looking to the future, nonhuman primate models of respiratory diseases will continue to be instrumental for translating biomedical research for improvement of human health.

Assessing Animal Models of Bacterial Pneumonia Used in Investigational New Drug Applications for the Treatment of Bacterial Pneumonia

“…and ventilator-associated pneumonia models. Signs and symptoms of bacterial pneumonia can be comparable between humans and nonhuman primates since the lungs of nonhuman primates resemble those of humans with respect to anatomy and physiology (4,6). With all the additional advantages of large animals, as the size of the animals increases, the facility requirements and personnel costs also increase, which may impact the feasibility of studies.…”

Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection

“…Nonhuman primates (NHPs) such as Macaca fascicularis are naturally susceptible to K. pneumoniae infections, many of which manifest as a respiratory disease (18). Moreover, the anatomy of the NHP respiratory system closely reflects that of humans (19,20). As a first step toward testing the ability of ST258 CPS to elicit a protective immune response in the host, we developed an ST258 model of lower respiratory tract infection in cynomolgus macaques ( Fig.…”

“…We chose NHPs to model K. pneumoniae respiratory infections due in large part to close approximation of human airway and lung anatomy, physiology and mucosal immune mechanisms. For example, primate species are distinguished by dichotomous branching of upper airways and progression to respiratory bronchioles that are not present in rodent species (19). Moreover, primate airways are highly ciliated in nature and have less abundant secretory cells than rodents (23).…”

Friends or foes? The knowns and unknowns of natural killer cell biology in COVID-19 and other coronaviruses in July 2020

“…The similar binding affinity of ACE2 in NHP allows them to be more permissive for viral replication. In addition, NHP are more comparable to humans in terms of lung anatomy, physiology, and immunology than rodent models [ 28 ]. SARS-CoV2–infected rhesus and cynomolgus macaques exhibited viral shedding in nasopharyngeal and oral samples, pneumonia and lung pathology characterized by diffuse alveolar damage (DAD), pulmonary edema and hyaline membrane formation, and accumulation of neutrophils, macrophages, and lymphocytes similar to COVID-19 patients [ 29 – 31 ].…”