Infant rhesus macaques as a non-human primate model of Bordetella pertussis infection

Na Gao,Peng Luo,Weilun Zuo,Jiangli Liang,Yan Ma,Qin Gu,Dachao Mou,Shuyuan Liu,Jingyan Li,Wenwen Jiang,Mingbo Sun,Li Shi,Xiao Ma,Chen Wei,Lichan Wang

doi:10.1186/s12879-021-06090-y

Abstract

BackgroundThe prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Rhesus macaques have been shown to be ideal animal models for several infectious diseases, but a model of infectious pertussis has not been established in these organisms. Studies on rhesus macaque models of pertussis were performed in the 1920s–1930s, but limited experimental details are available. Recent monkey pertussis models have not been successful because the typical clinical symptoms and transmission have not been achieved.MethodsIn the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using an aerosol method to evaluate the feasibility of this system as an animal model of pertussis.ResultsUpon aerosol infection, monkeys infected with the recently clinically isolated B.p strain 2016-CY-41 developed the typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and interanimal transmission of pertussis. Both systemic and mucosal humoral responses were induced by B.p.ConclusionThese results demonstrate that a model of pertussis was successfully established in infant rhesus macaques. This model provides a valuable platform for research on pertussis pathogenesis and evaluation of vaccine candidates.

Highlights

The prevalent resurgence of pertussis has recently become a critical public health problem worldwide
We investigated clinical symptoms, including leukocytosis, coughing, and nasopharyngeal colonization; analysed the humoral and mucosal immune response and cytokine levels; and performed a transmission test to evaluate the suitability of infant rhesus macaques as a potential alternative non-human primate (NHP) model for pertussis
The polymorphisms in the PT promoter, PT subunit 1, pertactin, fimbrial2 and fim3 were assessed by DNA sequencing

Summary

Introduction

The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. Low-grade fever, paroxysmal coughing, leukocytosis, a long-lived antipertussis toxin (PT) antibody response, protection against subsequent challenge, and transmission have been achieved in this baboon model, which makes the model crucial for studies on the pertussis pathogenic mechanism as well as for the development of new vaccines and therapeutics [11]. Another NHP, the rhesus macaque, has been evaluated for use as a pertussis model since 1929, but none of the studies have been able to completely replicate the human clinical disease [12,13,14]. While baboon models suffer from limited availability, high housing costs, and a lack of suitable reagents for use in these monkeys, rhesus macaques are more readily available and have low housing costs, and suitable reagents are available [17]

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Discussion

Conclusion