How do acellular vaccines compare with whole-cell pertussis vaccines for preventing whooping cough in children?

2014 ◽  
Author(s):  
Smitha Bhat
Keyword(s):  
Whooping Cough ◽  
Whole Cell ◽  
Acellular Vaccines

Pertussis

2021 ◽  
Author(s):  
Carl Heinz Wirsing von König
Keyword(s):  
Whooping Cough ◽  
Severe Disease ◽  
Newborn Infants ◽  
School Entry ◽  
Whole Cell ◽  
Young Infants ◽  
Combination Vaccines ◽  
Adolescents And Adults ◽  
Second Year ◽  
Acellular Vaccines

The bacterium Bordetella pertussis causes disease by producing various virulence and adhesion factors, among them pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and agglutinogens (Agg), also called fimbriae (FIM) "Typical" pertussis or whooping cough starts with unspecific respiratory symptoms (catarrhal phase) followed by severe coughing spasms with whoops and vomiting (paroxysmal phase) and only after weeks or months disease severity slowly wanes (convalescent phase). "Atypical pertussis" with unspecific, long-lasting coughing episodes is seen in adolescents and adults; very young infants may die from apnoea. B. pertussis is transmitted by droplets, and neither infection nor vaccination produce long lasting protection. Macrolide antibiotics are given to patients and their contacts to reduce spread of the organism; however, antibiotics do NOT change the duration or course of the disease once symptoms are present. Whole cell pertussis vaccines (wP) consist of whole inactivated B. pertussis-cells, whereas acellular vaccines (aP) consist of one to five single components like PT, FHA, PRN or FIM. Pertussis vaccines are currently only available as combination vaccines with tetanus und diphtheria (DTP). Among these are DTwP; DTaP; TdaP; and various DTP-combinations with Hib, IPV, HBV vaccines. Whole cell pertussis (DTwP) combination vaccines are more reactogenic, whereas DTaP vaccines are generally well tolerated. Some DTwP had good efficacy/effectiveness (90%), it was low (40%) with others. Vaccine efficacy of DTaP vaccines ranges between 70% and 90%. As with most vaccines, efficiency is higher for severe disease. While pertussis vaccines did control clinical disease, protection is limited. Vaccination is recommended for all infants (three doses) worldwide with a booster in the second year of life. Many countries give additional doses at school entry and in adolescents, and some to adults. Vaccination of pregnant women effectively protects newborn infants and is increasingly recommended.

scholarly journals A qPCR assay for Bordetella pertussis cells that enumerates both live and dead bacteria

2019 ◽  
Author(s):  
Stacy Ramkissoon ◽  
Iain MacArthur ◽  
Muktar Ibrahim ◽  
Hans de Graaf ◽  
Robert C. Read ◽  
...  
Keyword(s):  
Causative Agent ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Quantitative Measure ◽  
Qpcr Assay ◽  
Whole Cell ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Acellular Vaccines ◽  
Future Utility

AbstractBordetella pertussis is the causative agent of whooping cough, commonly referred to as pertussis. Although the incidence of pertussis was reduced through vaccination, during the last thirty years it has returned to high levels in a number of countries. This resurgence has been linked to the switch from the use of whole-cell to acellular vaccines. Protection afforded by acellular vaccines appears to be short-lived compared to that afforded by whole cell vaccines. In order to inform future vaccine improvement by identifying immune correlates of protection, a human challenge model of B. pertussis colonisation has been developed. Accurate measurement of colonisation status in this model has required development of a qPCR-based assay to enumerate B. pertussis in samples that distinguishes between viable and dead bacteria. Here we report the development of this assay and its performance in the quantification of B. pertussis from human challenge model samples. This assay has future utility in diagnostic labs and in research where a quantitative measure of both B. pertussis number and viability is required.

Pertussis

2021 ◽  
Author(s):  
Carl Heinz Wirsing von König
Keyword(s):  
Whooping Cough ◽  
Severe Disease ◽  
Newborn Infants ◽  
School Entry ◽  
Whole Cell ◽  
Young Infants ◽  
Combination Vaccines ◽  
Adolescents And Adults ◽  
Second Year ◽  
Acellular Vaccines

The bacterium Bordetella pertussis causes disease by producing various virulence and adhesion factors, among them pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and agglutinogens (Agg), also called fimbriae (FIM) "Typical" pertussis or whooping cough starts with unspecific respiratory symptoms (catarrhal phase) followed by severe coughing spasms with whoops and vomiting (paroxysmal phase) and only after weeks or months disease severity slowly wanes (convalescent phase). "Atypical pertussis" with unspecific, long-lasting coughing episodes is seen in adolescents and adults; very young infants may die from apnoea. B. pertussis is transmitted by droplets, and neither infection nor vaccination produce long lasting protection. Macrolide antibiotics are given to patients and their contacts to reduce spread of the organism; however, antibiotics do NOT change the duration or course of the disease once symptoms are present. Whole cell pertussis vaccines (wP) consist of whole inactivated B. pertussis-cells, whereas acellular vaccines (aP) consist of one to five single components like PT, FHA, PRN or FIM. Pertussis vaccines are currently only available as combination vaccines with tetanus und diphtheria (DTP). Among these are DTwP; DTaP; TdaP; and various DTP-combinations with Hib, IPV, HBV vaccines. Whole cell pertussis (DTwP) combination vaccines are more reactogenic, whereas DTaP vaccines are generally well tolerated. Some DTwP had good efficacy/effectiveness (90%), it was low (40%) with others. Vaccine efficacy of DTaP vaccines ranges between 70% and 90%. As with most vaccines, efficiency is higher for severe disease. While pertussis vaccines did control clinical disease, protection is limited. Vaccination is recommended for all infants (three doses) worldwide with a booster in the second year of life. Many countries give additional doses at school entry and in adolescents, and some to adults. Vaccination of pregnant women effectively protects newborn infants and is increasingly recommended.

scholarly journals The relationship between mucosal immunity, nasopharyngeal carriage, asymptomatic transmission and the resurgence of Bordetella pertussis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1568 ◽  
Author(s):  
Christopher Gill ◽  
Pejman Rohani ◽  
Donald M Thea
Keyword(s):  
Bordetella Pertussis ◽  
Mucosal Immunity ◽  
Whooping Cough ◽  
Critical Factor ◽  
Nasopharyngeal Carriage ◽  
Whole Cell ◽  
The Us ◽  
Acellular Vaccines ◽  
The Uk ◽  
The Relationship

The incidence of whooping cough in the US has been rising slowly since the 1970s, but the pace of this has accelerated sharply since acellular pertussis vaccines replaced the earlier whole cell vaccines in the late 1990s. A similar trend occurred in many other countries, including the UK, Canada, Australia, Ireland, and Spain, following the switch to acellular vaccines. The key question is why. Two leading theories (short duration of protective immunologic persistence and evolutionary shifts in the pathogen to evade the vaccine) explain some but not all of these shifts, suggesting that other factors may also be important. In this synthesis, we argue that sterilizing mucosal immunity that blocks or abbreviates the duration of nasopharyngeal carriage of Bordetella pertussis and impedes person-to-person transmission (including between asymptomatically infected individuals) is a critical factor in this dynamic. Moreover, we argue that the ability to induce such mucosal immunity is fundamentally what distinguishes whole cell and acellular pertussis vaccines and may be pivotal to understanding much of the resurgence of this disease in many countries that adopted acellular vaccines. Additionally, we offer the hypothesis that observed herd effects generated by acellular vaccines may reflect a modification of disease presentation leading to reduced potential for transmission by those already infected, as opposed to inducing resistance to infection among those who have been exposed.

scholarly journals Assays for Determining Pertussis Toxin Activity in Acellular Pertussis Vaccines

Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 417 ◽  
Author(s):  
Kevin Markey ◽  
Catpagavalli Asokanathan ◽  
Ian Feavers
Keyword(s):  
Molecular Structure ◽  
Quality Control ◽  
Virulence Factor ◽  
Pertussis Toxin ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Physiological Effects ◽  
Whole Cell ◽  
Acellular Vaccines ◽  
Main Component

Whooping cough is caused by the bacterium Bordetella pertussis. There are currently two types of vaccines that can prevent the disease; whole cell vaccines (WCV) and acellular vaccines (ACV). The main virulence factor produced by the organism is pertussis toxin (PTx). This toxin is responsible for many physiological effects on the host, but it is also immunogenic and in its detoxified form is the main component of all ACVs. In producing toxoid for vaccines, it is vital to achieve a balance between sufficiently detoxifying PTx to render it safe while maintaining enough molecular structure that it retains its protective immunogenicity. To ensure that the first part of this balancing act has been successfully achieved, assays are required to accurately measure residual PTx activity in ACV products accurately. Quality control assays are also required to ensure that the detoxification procedures are robust and stable. This manuscript reviews the methods that have been used to achieve this aim, or may have the potential to replace them, and highlights their continuing requirement as vaccines that induce a longer lasting immunity are developed to prevent the re-occurrence of outbreaks that have been observed recently.

Bordetella infection

2020 ◽  
pp. 1073-1076
Author(s):  
Cameron C. Grant
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Severe Disease ◽  
Diagnostic Methods ◽  
Illness Onset ◽  
Young Infants ◽  
Adolescents And Adults ◽  
Risk Of Exposure ◽  
Acellular Vaccines ◽  
Infectious Organism

Bordetella are small Gram-negative coccobacilli, of which Bordetella pertussis is the most important human pathogen. Bordetella pertussis is the cause of whooping cough, which remains one of the 10 leading causes of death among children less than five years old. Transmission of this highly infectious organism is primarily by aerosolized droplets. The preferred diagnostic methods are polymerase chain reaction detection from nasopharyngeal samples and serology (IgG antibodies to pertussis toxin). Macrolide antibiotics are recommended if started within four weeks of illness onset. Preventing severe disease in young children remains the primary goal, hence schedules consist of a three-dose infant series and subsequent booster doses. Acellular vaccines enable immunization schedules to include adolescents and adults. Acellular pertussis vaccine given to pregnant women reduces the risk of pertussis in young infants. Antibiotic prophylaxis is given when there is an infant at risk of exposure.

scholarly journals Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 594
Author(s):  
Jesús Arenas ◽  
Elder Pupo ◽  
Coen Phielix ◽  
Dionne David ◽  
Afshin Zariri ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Lipid A ◽  
Whooping Cough ◽  
Acyl Chain ◽  
In Vitro Assays ◽  
Whole Cell ◽  
Whole Cells ◽  
Acyl Chain Length ◽  
Acyl Chains

Whooping cough, or pertussis, is an acute respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis. Whole-cell vaccines, which were introduced in the fifties of the previous century and proved to be effective, showed considerable reactogenicity and were replaced by subunit vaccines around the turn of the century. However, there is a considerable increase in the number of cases in industrialized countries. A possible strategy to improve vaccine-induced protection is the development of new, non-toxic, whole-cell pertussis vaccines. The reactogenicity of whole-cell pertussis vaccines is, to a large extent, derived from the lipid A moiety of the lipopolysaccharides (LPS) of the bacteria. Here, we engineered B. pertussis strains with altered lipid A structures by expressing genes for the acyltransferases LpxA, LpxD, and LpxL from other bacteria resulting in altered acyl-chain length at various positions. Whole cells and extracted LPS from the strains with shorter acyl chains showed reduced or no activation of the human Toll-like receptor 4 in HEK-Blue reporter cells, whilst a longer acyl chain increased activation. Pyrogenicity studies in rabbits confirmed the in vitro assays. These findings pave the way for the development of a new generation of whole-cell pertussis vaccines with acceptable side effects.

scholarly journals InvestigatingBordetella pertussiscolonisation and immunity: protocol for an inpatient controlled human infection model

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e018594 ◽  
Author(s):  
Hans de Graaf ◽  
Diane Gbesemete ◽  
Andrew R. Gorringe ◽  
Dimitri A. Diavatopoulos ◽  
Kent E. Kester ◽  
...  
Keyword(s):  
Human Infection ◽  
Control Group ◽  
Infection Model ◽  
Whole Cell ◽  
Open Access Journals ◽  
Two Phases ◽  
Acellular Vaccines ◽  
Developed World ◽  
Healthy Participants

IntroductionWe summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. GloballyBordetella pertussisis one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage. The acellular vaccine provides relatively short-lived immunity and, in contrast to whole cell vaccines, may be less effective against colonisation and subsequent transmission. To improve vaccine strategies, a greater understanding of humanB. pertussiscolonisation is required. This article summarises a protocol and does not contain any results.Methods and analysisA controlled human colonisation model will be developed over two phases. In phase A, a low dose of the inoculum will be given intranasally to healthy participants. This dose will be escalated or de-escalated until colonisation is achieved in approximately 70% (95% CI 47% to 93%) of the exposed volunteers without causing disease. The colonisation period, shedding and exploratory immunology will be assessed during a 17-day inpatient stay and follow-up over 1 year. The dose of inoculum that achieves 70% colonisation will then be confirmed in phase B, comparing healthy participants exposed toB. pertussiswith a control group receiving a sham inoculum.Ethics and disseminationThis study has been approved by the ethical committee reference: 17/SC/0006, 24 February 2017. Findings will be published in peer-reviewed open access journals as soon as possible.

PAT for vaccines: The first stage of PAT implementation for development of a well-defined whole-cell vaccine against whooping cough disease

Vaccine ◽  
2007 ◽  
Vol 25 (16) ◽  
pp. 2994-3000 ◽  
Author(s):  
Mathieu Streefland ◽  
Bas van de Waterbeemd ◽  
Hester Happé ◽  
Leo A. van der Pol ◽  
E. Coen Beuvery ◽  
...  
Keyword(s):  
Whooping Cough ◽  
Cell Vaccine ◽  
Whole Cell ◽  
Whole Cell Vaccine

Acellular and Whole-Cell Pertussis Vaccines as Booster Doses: A Multicenter Study

PEDIATRICS ◽  
1994 ◽  
Vol 93 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Janet A. Englund ◽  
Michael D. Decker ◽  
Kathryn M. Edwards ◽  
Michael E. Pichichero ◽  
Mark C. Steinhoff ◽  
...  
Keyword(s):  
Public Health ◽  
Antibody Response ◽  
Multicenter Study ◽  
Adverse Reactions ◽  
Pain Medication ◽  
Antibody Responses ◽  
Whole Cell ◽  
Acellular Vaccines ◽  
Antibody Levels ◽  
Better Than

Objective. To compare the safety and immunogenicity of a variety of acellular (AC) and whole-cell (WC) pertussis vaccines combined with diphtheria and tetanus toxoids. Methods. Standard enrollment and reaction forms were used at five sites, and serologic evaluation was performed at a single site. Nine AC (Massachusetts Public Health Laboratories, Biocine Sclavo recombinant pertussis toxoid [PT], Connaught/BIKEN, Lederle three-component, Biocine Sclavo recombinant three-component, SmithKline Beecham three-component, Porton three-component, Takeda-Wyeth, and Connaught multicomponent), and three WC (Connaught Laboratoties, Lederle Laboratories, and Massachusetts Public Health Laboratories) were studied. All AC contained varying concentrations of PT; some vaccines also contamed filamentous hemagglutinin (FHA), pertactin, and/or agglutinogens. Results. Two hundred forty children, aged 16 to 21 months and 4 to 6 years, were enrolled at five sites. Significantly less fever, redness, swelling, pain, limp, and use of pain medication were noted following AC compared with WC. Significant increases in antibody to PT were seen following all vaccines. Significant rises in FHA antibody were seen following all WC and the seven AC that contained FHA. Postbooster PT antibody levels were similar among the AC groups, regardless of the amount of PT administered (between 3.5 and 25 µg per dose). The dose of FHA did not affect PT antibody response. Infants primed with WC who were boosted with a monocomponent PT vaccine did not manifest a significant antibody response to FHA. Conclusion. The rate of adverse reactions was not a function of the number of antigens or the antigen quantity in the acellular vaccines, and antibody responses following AC were similar or better than antibody responses following WC. These results support the further evaluation of these vaccines in a larger National Institute of Allergy and Infectious Diseases-sponsored study in infants.

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