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):  
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.

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 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.

Cleft Nucleus Lymphocytosis in Young Infants with Pertussis

2020 ◽  
Author(s):  
Huifang Zhu ◽  
Hongqun Liao ◽  
Xiaoming Zhong ◽  
Xingyu Rao ◽  
Xin Yang ◽  
...  
Keyword(s):  
Young Children ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Pediatric Intensive Care ◽  
Peripheral Blood Smear ◽  
Significant Rise ◽  
Enzyme Linked Immunosorbent Assay ◽  
Respiratory Pathogens ◽  
Pertussis Infection ◽  
Young Infants

AbstractThis study aims to assess whether the cleft nucleus lymphocytosis could be an early promising clue for the diagnosis of pertussis in young infants. Pertussis (whooping cough) is a severe respiratory disease mainly caused by Bordetella pertussis infection and is characterized by a significant rise in the number of leukocyte and lymphocyte in infants and young children. In this study, the Bordetella pertussis DNA was detected from samples of pharyngeal swab by PCR assay. Levels of serum specific IgM against other respiratory pathogens were detected by Enzyme-linked immunosorbent assay (ELISA) assay. The routine blood test including numbers of leukocytes, lymphocytes, and platelets etc. were tested by automatic hemocyte analyzer (Sysemx XN1000). Besides, the morphology of leucocytes was observed in peripheral blood smear with microscope by Wright-Giemsa stain. Three cases of pertussis with cleft nucleus lymphocytes in young infants were discussed in in the neonatal/pediatric intensive care unit in our hospital. Leukocytosis characterized by lymphocytes, as well as thrombocytosis were observed in all patients. Our results demonstrated that cleft nucleus lymphocytosis accompanied with leukocytosis and lymphocytes would be potent assistant indicators for the early diagnosis of pertussis in young children.

scholarly journals Next-Generation Pertussis Vaccines Based on the Induction of Protective T Cells in the Respiratory Tract

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 621 ◽  
Author(s):  
Caitlín Ní Chasaide ◽  
Kingston H.G. Mills
Keyword(s):  
Respiratory Tract ◽  
Protective Immunity ◽  
Membrane Vesicle ◽  
Secretory Iga ◽  
Nasal Colonization ◽  
Next Generation ◽  
Previous Infection ◽  
Cellular Immune

Immunization with current acellular pertussis (aP) vaccines protects against severe pertussis, but immunity wanes rapidly after vaccination and these vaccines do not prevent nasal colonization with Bordetella pertussis. Studies in mouse and baboon models have demonstrated that Th1 and Th17 responses are integral to protective immunity induced by previous infection with B. pertussis and immunization with whole cell pertussis (wP) vaccines. Mucosal Th17 cells, IL-17 and secretory IgA (sIgA) are particularly important in generating sustained sterilizing immunity in the nasal cavity. Current aP vaccines induce potent IgG and Th2-skewed T cell responses but are less effective at generating Th1 and Th17 responses and fail to prime respiratory tissue-resident memory T (TRM) cells, that maintain long-term immunity at mucosal sites. In contrast, a live attenuated pertussis vaccine, pertussis outer membrane vesicle (OMV) vaccines or aP vaccines formulated with novel adjuvants do induce cellular immune responses in the respiratory tract, especially when delivered by the intranasal route. An increased understanding of the mechanisms of sustained protective immunity, especially the role of respiratory TRM cells, will facilitate the development of next generation pertussis vaccines that not only protect against pertussis disease, but prevent nasal colonization and transmission of B. pertussis.

Erythromycin Prophylaxis for Pertussis

PEDIATRICS ◽  
1977 ◽  
Vol 59 (4) ◽  
pp. 623-625 ◽  
Author(s):  
W. A. Altemeier ◽  
E. M. Ayoub
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Clinical Disease ◽  
Pertussis Infection ◽  
Limited Experience

A neonate admitted to the newborn nursery was found to have bacteriologically proven Bordetella pertussis whooping cough, and two of seven infants exposed to this child became infected. Erythromycin administration to the seven infants apparently prevented further infection as well as the appearance of clinical disease in the two infected infants. This limited experience supports previous reports of the efficacy of erythromycin in preventing B. pertussis infection and disease in susceptible children.

Vaccine-driven selection and the changing molecular epidemiology of Bordetella pertussis

Pertussis ◽  
2018 ◽  
pp. 166-181
Author(s):  
Ruiting Lan ◽  
Sophie Octavia
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Pertussis Toxin ◽  
Bordetella Pertussis ◽  
Vaccine Coverage ◽  
Toxin Production ◽  
Developed Countries ◽  
Single Nucleotide ◽  
Genetic Changes ◽  
Vaccine Preventable Diseases ◽  
Acellular Vaccine

Pertussis remains one of the least controlled vaccine-preventable diseases despite high vaccine coverage in many countries. There are ongoing debates about the causes of its resurgence. Major changes have occurred in the Bordetella pertussis population since the introduction of vaccination. Currently circulating strains in Australia and many other developed countries are grouped in single nucleotide polymorphism (SNP) cluster I (also known as ptxP3 strains). The emergence and expansion of SNP cluster I has been associated with two major genetic changes in B. pertussis: a change in its pertussis toxin promoter (to ptxP3) which leads to increased pertussis toxin production and the change of the acellular vaccine pertactin gene allele to prn2. More recently, strains that lack pertactin have emerged independently in different lineages. The resurgence of pertussis in highly vaccinated populations can be, at least in part, explained by genetic changes that increase the fitness of circulating B. pertussis strains.

Sign in / Sign up

Export Citation Format

Share Document