In the s, the acellular vaccine was introduced in the US and gradually replaced the whole-cell vaccine. About 10 years later, a possible failure with the new vaccine has been observed, that is a lack of long-term protection. Nowadays, both vaccines are used, with the acellular vaccine being vastly predominant in most developed countries. Pertussis incidence has increased since the s, but new prevention strategies include booster doses for specific age groups. Thus, Dr. Wilson spearheaded work on a DP vaccine, which combined pertussis vaccine with the well-established diphtheria toxoid to protect children against both diseases at the same time.
By the mids, simultaneous protection against tetanus was also possible with DPT. Similarly, after the introduction of the first polio vaccine in , Connaught took the global lead in developing a new generation of combined vaccines, known as DPT-Polio, DT-Polio and T-Polio, which were launched in Some parents declined to have their children immunized against pertussis, and some countries, such as Sweden and Japan, scaled back or suspended their pertussis immunization programs, inevitably resulting in significant spikes in pertussis incidence.
It would be prepared from only the key components of the bacteria necessary to stimulate immunity. A team of researchers at Connaught first focused on isolating the pertussis toxin, the primary antigenic component of the B. This team next developed methods to isolate four additional critical components of the bacterium. They also pioneered a more efficient method for final chemical detoxification of these components, which were then standardized and expanded for large-scale production.
However, even with the new generation of pertussis vaccine, many still suffer from pertussis and there are periodic outbreaks of the disease in Canada and elsewhere. World wide, whooping cough still affects Significant sources of increased incidence in recent years have been adolescents and adults. Pertussis immunity from childhood vaccinations fades over time, thus leaving older people vulnerable to pertussis infections.
And while the disease is not as dangerous to adolescent and adults, they can easily transmit it to un-immunized, or incompletely immunized, young children and infants. Bordetella pertussis bacteria Image source: Sanofi Pasteur Canada. Child with pertussis whooping cough. Pertussis incidence in Ontario, Image source: Sanofi Pasteur Canada.
Pertussis incidence in Canada, Infectious diseases isolation instructions, c. Jules Bordet, identified Bordetella pertussis as cause of the disease, Pertussis vaccine production record, Connaught Laboratories, March Note the standard strains used. Pertussis vaccine standard strain , Lederle Laboratories, c. Museum of Health Care, accession The first epidemic was described in by Guillaume de Baillou [ 7 , 8 ].
The genome of a reference strain for these 3 species was sequenced [ 9 ], and their phylogenetic relationship was studied in detail [ 10 ]. They evolved through genome reduction with large-scale rearrangements [ 10 ].
Insertion sequence IS elements played a particularly important part in the reduction of the B. Furthermore, comparative genomic hybridization and multilocus sequence typing studies [ 12 ] have shown that the degree of genetic diversity is greatest in B.
These data suggest that the association of B. It is highly labile and cannot survive outside its host. Thus, its aim is to survive in its host, and accordingly, it has maintained its capacity to transmit very efficiently from one host to another. The study of human-specific pathogens requires collaboration with clinicians and epidemiologists or the development of appropriate animal models.
Various models have been proposed or used to study the pathogenicity of B. Primates are not used because of the high cost, and the major limitation in mouse and piglet models is the nontransmission of the disease in these animals.
Although mice do not have the muscle that allows coughing, they can still be useful in the characterization of virulence factors and analysis of certain aspects of the immune response to infection. It produces several bacterial factors responsible for the symptoms observed during the disease [ 13 ]. These include several toxins eg, tracheal cytotoxin; pertussis toxin, an A-B toxin; and adenylate cyclase-hemolysin, a Repeats in ToXins [RTX] toxin that damage ciliated epithelial cells and alveolar macrophages and cause hyperlymphocytosis.
The bacterium also produces several adhesins, such as filamentous hemagglutinin, pertactin, and 2 fimbrial proteins FIM2 and FIM3. Soon after the isolation of the bacterium, Pw vaccines were developed using heat-killed bacteria. Given the pediatric nature of the disease, infants and toddlers were intensively vaccinated. The B. Analyses performed over the past 2 decades demonstrate that several types of isolates, which produce various proteins, had been in circulation during the prevaccine era.
However, 1 or 2 types predominated, with no significant geographical pattern observed in their distribution. Pw vaccines are generally composed of 1, 2, or 3 different strains, which are selected from these predominant types. Extensive analyses over the past decade compare clinical isolates circulating during the prevaccine era with those that now remain in circulation [ 12 , 14 ]. In areas where Pw vaccination in infants and toddlers was effective, vaccine strains were no longer circulating or circulated at a very low level.
In a previous study, my colleagues and I did not find differences between isolates circulating in areas using the same vaccine and the same schedule, with similar coverage [ 15 , 16 ]. In countries sharing the same vaccine schedules and coverage, but using vaccine strains with different fimbriae, the isolates now circulating in these different regions were similar but, accordingly, produced different fimbriae [ 17 ].
In areas with very low vaccine coverage, isolates remaining in circulation are similar to those that were circulating in the pre-vaccine era [ 18 ]. Thus, overall, the effective use of Pw vaccines to induce immunity controlled the circulation of some—but not all—isolates. The remaining isolates that are currently in circulation have been shown to be as virulent as the isolates that were circulating in the prevaccine era [ 18 ].
However, genomic analyses have demonstrated that they exhibit several differences with the vaccine strains and the prevaccine era isolates. Their genome possesses less genetic material but more IS elements than the isolates circulating during the prevaccine era [ 19 ]. The genetic material lost is composed mostly of pseudo-genes but no gene implicated in the survival inside the host or in the virulence of the bacteria.
As the number of pseudo-genes decreases, B. It thus remains possible that B. IS elements may be of particular importance due to their potential role in the initiation of gene duplication or deletion events.
As described initially by Bordet and Gengou [ 1 ], and as observed since by scientists isolating this bacterium from nasopharyngeal samples, the phenotype of freshly isolated bacteria in biological samples differs from that of the bacteria grown in vitro. We previously demonstrated that certain clinical isolates of B.
This phenomenon explains the observation of the larger halo of haemolysis produced by these isolates in BG medium than produced by other clinical isolates [ 20 ]. However, 1 gene is deleted after 2 or 3 subcultures, with this process being mediated by IS elements. Thus, new B. Pw vaccination induces a broad immune response against hundreds of bacterial proteins, leading to the control of the circulation of isolates similar to the vaccine strains.
However, this vaccination approach did not control the circulation of other isolates and did not control the virulence of the isolates. These Pa vaccines consist of 1—5 purified, detoxified toxins and adhesins. They consequently induce immunity against only a few bacterial proteins involved in the virulence of the bacterium.
Thus, vaccine-induced immunity is changing, with bacterial virulence becoming the major target. Furthermore, the overall immunity in the human population is increasing, because Pa vaccines are not only used for infants and toddlers but also for adolescents and adults. With the use of Pa vaccines and increased vaccine coverage, successful control B. What mechanisms underlie this potential control of virulence?
We recently found that currently circulating isolates have more IS elements in their genome than isolates circulating during the prevaccine era [ 19 ]. As explained above, these IS elements are often located at both ends of a structural gene and can lead to gene deletion.
Therefore, with an increasing rate of Pa vaccine-induced immunity in the population, we would expect newly collected isolates to lack the vaccine antigens due to deletion or inactivation of their structural genes.
Indeed, since , there have been several such isolates reported, some of which do not produce pertussis toxin and others not producing pertactin [ 22 ]. The absence of expression of these vaccine antigens is due either to deletion of the structural gene or to an IS element insertion within the structural gene. France may be particularly suited to the collection of such isolates, because its vaccine coverage is one of the highest in the world. If Pa vaccines are now used for the universal vaccination of adults, the circulation of virulent B.
With an increasing coverage of Pa vaccine, B. However, will these isolates be less virulent? This important question is currently being investigated. However, the analysis requires the regular collection of isolates. Freshly collected isolates, however, are becoming increasingly difficult to obtain. Indeed, because of the difficulties in isolating the bacteria, culture is now being replaced by polymerase chain reaction. In addition, infected adults do not tend to visit their general practitioners immediately, during the earliest stages of the disease, preventing isolation of the bacterium in these cases.
Furthermore, this tendency might increase if circulating isolates are less virulent. Isolates can be more easily collected from newborns and infants. Their immune system is immature, and B. Hospital-based surveillance thus probably offers one of the best systems in which to analyze not only the progression of the disease in infants but also in adults in contact with infected infants.
The Pa vaccine-induced immune response targets the virulence of B.
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