scholarly journals Infant Rhesus Macaques as a Nonhuman Primate Model of Bordetella Pertussis

2020 ◽  
Author(s):  
Li Shi ◽  
Wenwen Jiang ◽  
Chen Wei ◽  
Dachao Mou ◽  
Weilun Zuo ◽  
...  
Keyword(s):  
Animal Model ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Rhesus Macaques ◽  
Public Health Problem ◽  
Primate Model ◽  
Pertussis Infection ◽  
Cellular Immune ◽  
Infant Rhesus ◽  
Human Primate

Abstract Background: The prevalent resurgence of pertussis recently creates a vital public health problem worldwide. To understand the pertussis pathogenesis and host response to both pathogen and vaccine, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a successful non-human primate pertussis model of baboons have been established. However, though the rhesus macaques have been proven to be ideal animal models for several infectious diseases, the infectious model of pertussis has not been established on it. The previous studies on rhesus macaque models of pertussis were performed in 1920s-1930s with limited experimental details. Recent monkey pertussis models failed to be established because the typical clinic syndrome and transmission were not investigated.Methods: In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using the aerosol method to evaluate the feasibility of using it as an animal model of pertussis infection.Results: Upon aerosol infection, monkeys infected with the recent clinically isolated B.p strain 2016-CY-41 developed typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and inter-animal transmission. Both humoral and cellular immune responses were induced by B.pertussis.Conclusion: These results demonstrate that a model of pertussis infection was successfully established in infant rhesus macaques, which provides a valuable platform to study pertussis pathogenesis and evaluate vaccine candidates.

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

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wenwen Jiang ◽  
Chen Wei ◽  
Dachao Mou ◽  
Weilun Zuo ◽  
Jiangli Liang ◽  
...  
Keyword(s):  
Animal Model ◽  
Bordetella Pertussis ◽  
Clinical Symptoms ◽  
Whooping Cough ◽  
Rhesus Macaques ◽  
Public Health Problem ◽  
Primate Model ◽  
Pertussis Infection ◽  
Infant Rhesus ◽  
Human Primate

Abstract Background The 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. Methods In 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. Results Upon 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. Conclusion These 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.

The immunology of Bordetella pertussis infection and vaccination

Pertussis ◽  
2018 ◽  
pp. 42-65
Author(s):  
Mieszko M. Wilk ◽  
Aideen C. Allen ◽  
Alicja Misiak ◽  
Lisa Borkner ◽  
Kingston H.G. Mills
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Vaccine Coverage ◽  
Immunological Memory ◽  
Nasal Colonization ◽  
Pertussis Infection ◽  
Genetic Changes ◽  
Antibody Titres ◽  
Previous Infection ◽  
Cellular Immune

Bordetella pertussis causes whooping cough (pertussis), a severe and sometimes fatal respiratory infectious disease, especially in young infants. Pertussis can be prevented in infants and children by immunization with either whole-cell pertussis (wP) or acellular pertussis (aP) vaccines; however, its incidence is increasing in many countries despite high vaccine coverage. This resurgence in populations immunized with aP vaccines has been attributed to (1) genetic changes in circulating strains of B. pertussis resulting from vaccine-driven immune selection, (2) waning protective immunity due to poor induction of immunological memory, or (3) a failure of aP vaccines to induce the appropriate arm(s) of the cellular immune responses required to prevent infection. Studies in a baboon model have suggested that previous infection prevents reinfection as well as disease, whereas aP vaccines fail to prevent nasal colonization and transmission of B. pertussis. Studies in the mouse model have demonstrated that immunization with wP vaccines induces Th1 and Th17 responses, whereas aP vaccines promote Th2-skewed responses and high antibody titres. Thus, while aP vaccine-induced antibodies may prevent pertussis, they may not prevent nasal colonization or transmission. Emerging data have suggested that replacing alum with novel adjuvants based on pathogen-associated molecular patterns has the capacity to switch the responses induced with aP vaccines to the more protective Th1/Th17 responses and may also enhance immunological memory. It is likely that third-generation pertussis vaccines will be based on live attenuated bacteria or aP formulations with novel adjuvants, which prevent nasal and lung infection and induce sustained immunity through induction of memory T cells.

scholarly journals Infant Rhesus Macaques as a Nonhuman Primate Model of Bordetella pertussis

2020 ◽  
Author(s):  
Wen-Wen Jiang ◽  
Chen Wei ◽  
Da-Chao Mou ◽  
Wei-Lun Zuo ◽  
Jiang-Li Liang ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Nonhuman Primate ◽  
Rhesus Macaques ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Infant Rhesus

Triggering receptor expressed on myeloid cells-1 (TREM-1) contributes to Bordetella pertussis inflammatory pathology

2021 ◽  
Author(s):  
Danisha Gallop ◽  
Karen Scanlon ◽  
Jeremy Ardanuy ◽  
Alexander B. Sigalov ◽  
Nicholas H. Carbonetti ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Inflammatory Responses ◽  
Whooping Cough ◽  
Pulmonary Inflammation ◽  
Myeloid Cells ◽  
Cell Surface Receptor ◽  
Bacterial Burden ◽  
Emerging Pathogens ◽  
Pertussis Infection ◽  
Bacterial Control

Whooping cough (pertussis) is a severe pulmonary infectious disease caused by the bacteria Bordetella pertussis . Pertussis infects an estimated 24 million people annually, resulting in >150,000 deaths. The NIH placed pertussis on the list of emerging pathogens in 2015. Antibiotics are ineffective unless administered before the onset of the disease characteristic cough. Therefore, there is an urgent need for novel pertussis therapeutics. We have shown that sphingosine-1-phosphate receptor (S1PR) agonists reduce pertussis inflammation, without increasing bacterial burden. Transcriptomic studies were performed to identify this mechanism and allow for the development of pertussis therapeutics which specifically target problematic inflammation without sacrificing bacterial control. These data suggested a role for triggering receptor expressed on myeloid cells-1 (TREM-1). TREM-1 cell surface receptor functions as an amplifier of inflammatory responses. Expression of TREM-1 is increased in response to bacterial infection of mucosal surfaces. In mice, B. pertussis infection results in TLR9-dependent increased expression of TREM-1 and its associated cytokines. Interestingly, S1PR agonists dampen pulmonary inflammation and TREM-1 expression. Mice challenged intranasally with B. pertussis and treated with ligand-dependent (LP17) and ligand-independent (GF9) TREM-1 inhibitors showed no differences in bacterial burden and significantly reduced TNF-α and CCL-2 expression compared to controls. Mice receiving TREM-1 inhibitors showed reduced pulmonary inflammation compared to controls indicating that TREM-1 promotes inflammatory pathology, but not bacterial control, during pertussis infection. This implicates TREM-1 as a potential therapeutic target for the treatment of pertussis.

Could this be whooping cough?

2018 ◽  
Vol 35 (10) ◽  
pp. 639-642 ◽  
Author(s):  
Patrick Nee ◽  
Elaine Weir ◽  
Madhur Vardhan ◽  
Ankita Vaidya
Keyword(s):  
Young Children ◽  
Clinical Features ◽  
Respiratory Infection ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Pertussis Infection ◽  
Respiratory Disorders ◽  
Very Young Children ◽  
Geographical Regions ◽  
Serious Disease

Whooping cough is a notifiable bacterial respiratory infection caused by Bordetella pertussis. It may produce serious disease, especially in immunocompromised individuals and very young children. The number of reported cases increases in the winter months and the incidence peaks every 4–5 years. However, this periodicity is variable and is inconsistent between different geographical regions. Bordetella pertussis infection (BPI) may be underdiagnosed because of its seasonality and the fact that clinical features may be indistinguishable from other respiratory disorders in the paediatric ED setting. Treatment with antibiotics reduces the period of infectivity but may not shorten the illness. This review discusses the epidemiology of the disease, its clinical features, diagnosis, treatment and the disposition of patients with BPI.

scholarly journals Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status

2020 ◽  
Vol 40 (7) ◽  
pp. 1415-1426 ◽  
Author(s):  
Di Wu ◽  
Jian Chen ◽  
Mohammed Hussain ◽  
Longfei Wu ◽  
Jingfei Shi ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Motor Dysfunction ◽  
Neurological Deficits ◽  
Brain Cooling ◽  
Long Term Outcomes ◽  
Primate Model ◽  
Tissue Plasminogen ◽  
Human Primate ◽  
Arterial Thrombolysis

Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes – complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.

scholarly journals Immunoglobulin A-Mediated Protection against Bordetella pertussis Infection

2001 ◽  
Vol 69 (8) ◽  
pp. 4846-4850 ◽  
Author(s):  
Sandra M. M. Hellwig ◽  
Annemiek B. van Spriel ◽  
Joop F. P. Schellekens ◽  
Frits R. Mooi ◽  
Jan G. J. van de Winkel
Keyword(s):  
Transgenic Mice ◽  
Bordetella Pertussis ◽  
Polymorphonuclear Leukocytes ◽  
Whooping Cough ◽  
Immunoglobulin A ◽  
Pertussis Infection ◽  
Bacterial Killing ◽  
Effector Functions ◽  
Human Polymorphonuclear Leukocytes

ABSTRACT Infection with Bordetella pertussis, the causative agent of pertussis (whooping cough) in humans, is followed by the production of antibodies of several isotypes, including immunoglobulin A (IgA). Little is known, however, about the role of IgA in immunity against pertussis. Therefore, we studied targeting ofB. pertussis to the myeloid receptor for IgA, FcαRI (CD89), using either IgA purified from immune sera of pertussis patients or bispecific antibodies directed against B. pertussis and FcαRI (CD89 BsAb). Both IgA and CD89 BsAb facilitated FcαRI-mediated binding, phagocytosis, and bacterial killing by human polymorphonuclear leukocytes (PMNL) and PMNL originating from human FcαRI-transgenic mice. Importantly, FcαRI targeting resulted in enhanced bacterial clearance in lungs of transgenic mice. These data support the capacity of IgA to induce anti-B. pertussis effector functions via the myeloid IgA receptor, FcαRI. Increasing the amount of IgA antibodies induced by pertussis vaccines may result in higher vaccine efficacy.

scholarly journals Bordetella pertussis infection in household contacts of cases of pertussis in the southeast zone of the city of Cali, Colombia, 2006-2007

2011 ◽  
pp. 184-190 ◽  
Author(s):  
Miryam Astudillo ◽  
Victoria Eugenia Estrada ◽  
Mónica Fernández de Soto ◽  
Luz Ángela Moreno
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Control Strategies ◽  
Epidemiological Data ◽  
Geographic Area ◽  
Asymptomatic Infection ◽  
Culture Technique ◽  
Pertussis Infection ◽  
Cross Sectional ◽  
Household Contacts

Introduction: Bordetella pertussis causes whooping cough or convulsive cough, a contagious and immune-preventable disease. It is one of the 10 leading causes of death among children younger than one year of age, when not completely immunized. It is considered reemerging in several countries, with high rates of complications and hospitalizations. Objective: to learn of the proportion of infection by B. pertussis among suspected cases of whooping cough and their household contacts among children from the southeast zone of Cali, a geographic area with great consultation demand due to this infection. Methodology: This is a cross-sectional descriptive study. Epidemiological data and nasopharyngeal samples were taken from 24 suspected cases and from their 109 household contacts. The samples were analyzed via real-time polymerase chain reaction (Q-PCR) and through culture. Results: The proportion of positivity among the cases via the Q-PCR technique was at 50% (12/24) and at 40% via the culture technique (8/20), with good agreement between both techniques (Kappa 0.61). Regarding the household contacts, 30.3% (33/109) (CI 95%: 21.8%-39.8%) tested positive. The sibling contacts (7/15) and the mothers (7/22) presented the greatest proportion of positivity. Regarding age, 60% were 4 years of age (3/5) and 50% were in the group comprised of individuals 45 to 64 years of age. No significant differences were found among the presence or absence of symptoms and the presence of B. pertussis infection, except for the presence of nasal secretions (runny nose) (27%) and coughing (36%) during the last month. Conclusions: The study confirms the high prevalence of asymptomatic infection by B. pertussis among household contacts of children with whooping cough symptomatology and its household transmission. In Cali, health authorities need to review the effectiveness of implemented control strategies and the use of a vaccination scheme that does not cover adolescent and adult populations as a focus of infection control.

scholarly journals Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque’s and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines

2018 ◽  
Author(s):  
Jonathan O. Rayner ◽  
Raj Kalkeri ◽  
Scott Goebel ◽  
Zhaohui Cai ◽  
Brian Green ◽  
...  
Keyword(s):  
Immune Response ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
New Drugs ◽  
Primate Model ◽  
Robust Immune Response ◽  
African Lineage ◽  
Limit Of Quantitation ◽  
Asian Lineage ◽  
Human Primate

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

scholarly journals Experimental infection characteristics ofBordetellapertussis via aerosol challenge on rhesus macaques

2018 ◽  
Author(s):  
Dachao Mou ◽  
Peng Luo ◽  
Jiangli Liang ◽  
Qiuyan Ji ◽  
Lichan Wang ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Rhesus Macaques ◽  
Seroconversion Rate ◽  
Geometric Mean ◽  
Human Beings ◽  
Pertussis Infection ◽  
Cell Counts ◽  
Baseline Levels ◽  
Group 2 ◽  
Infant Rhesus

AbstractThe effect of aerosol challenge of rhesus macaques withBordetella pertussisand the feasibility of using rhesus monkeys as an animal model for pertussis infection were evaluated in this study. Four 1-year old rhesus macaques were aerosol challenged withB. pertussisat the concentration of 105CFU/mL for 30 min (group 1) or 60 min (group 2). Rectal temperature was found slightly increased at days 3 and 5 and returned to baseline levels at day 21 after challenge. White blood cell counts peaked at day 7, with a 4.7~6.1-fold increase and returned to baseline levels at day 45. Bacteria colonization of nasopharyngeal swabs was observed, and the number of colonies was gradually increased and peaked at day 14, reaching 5.4-8.1 × 106/mL. The seroconversion rate of anti-pertussis toxin (PT), pertactin (PRN), and filamentous hemagglutinin(FHA) antibodies was 100%, with an increase in geometric mean titers after challenge. Analysis of cytokines revealed that the levels of cytokines including IL-2, IL-6, IL-8, IL-10, IL-17A, IL-13, IL-12, and IL-18 were significantly increased at days 5 to 14 in group 2. These results demonstrate that the characteristic of pertussis infection in infant rhesus macaque was similar as in human beings, which provide a clue to using infant rhesus macaque as a candidate model for pertussis infection in the future studies

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