Lack of Cross-protection against Bordetella holmesii after Pertussis Vaccination - - Emerging Infectious Disease journal - CDC
Lack of Cross-protection against Bordetella holmesii after Pertussis Vaccination
Bordetella pertussis and B. parapertussis commonly cause whooping cough, a highly contagious, acute coughing illness, in humans (1,2). Licensed in the mid-1940s, the first whooping cough vaccines consisted of whole-cell inactivated B. pertussis (wP), and their use led to a dramatic decrease in disease incidence by the mid-1960s (2,3). The potential for health risks related to wP vaccine, however, led to adaptation of acellular (aP) vaccines, which contain combinations of purified B. pertussis proteins. Despite high vaccine coverage, reported whooping cough incidence in industrialized countries has been increasing during the past 20 years, although this could be the result of greater awareness and improved analytical tools (4–9).
AbstractBordetella holmesii, a species closely related to B. pertussis, has been reported sporadically as a cause of whooping cough–like symptoms. To investigate whether B. pertussis–induced immunity is protective against infection with B. holmesii, we conducted an analysis using 11 human respiratory B. holmesii isolates collected during 2005–2009 from a highly B. pertussis–vaccinated population in Massachusetts. Neither whole-cell (wP) nor acellular (aP) B. pertussis vaccination conferred protection against these B. holmesii isolates in mice. Although T-cell responses induced by wP or aP cross-reacted with B. holmesii, vaccine-induced antibodies failed to efficiently bind B. holmesii. B. holmesii–specific antibodies provided in addition to wP were sufficient to rapidly reduce B. holmesii numbers in mouse lungs. Our findings suggest the established presence of B. holmesii in Massachusetts and that failure to induce cross-reactive antibodies may explain poor vaccine-induced cross-protection.
In November 1983, the Centers for Disease Control and Prevention (CDC) received a gram-negative bacterium isolated from an asplenic patient (10). During the following decade, additional clinical isolates with the same microbiological characteristics (slow-growing, gram-negative, small coccoid, asaccharolytic, oxidase negative, nonmotile and brown-soluble-pigment-producing) were submitted to the CDC for identification (10). Subsequent biochemical analysis, 16S rRNA sequencing, and DNA relatedness studies revealed that these strains were new Bordetella species, which was named Bordetella holmesii to honor Barry Holmes (10). Since then, this bacterium has been isolated from numerous countries, including Australia, Canada, Chile, France, Germany, Japan, Netherlands, Switzerland, the United Kingdom, and the United States (6–15). These findings indicate that B. holmesii is a widespread pathogen among populations that are highly vaccinated against B. pertussis.
Comparative analysis of B. holmesii and B. pertussis by using 16S rRNA suggests that B. holmesii is closely related to B. pertussis, but further analysis of cellular fatty acid composition, housekeeping genes, and the BvgAS locus suggests that B. holmesii may not share many of the highly conserved virulence factors of B. pertussis (16). Antibodies against B. pertussis pertactin, pertussis toxin, fimbriae, adenylate cyclase toxin, and filamentous hemagglutinin recognize few, if any, proteins from multiple B. holmesii isolates (14), results that suggest B. holmesii may be antigenically distinct from B. pertussis.
Although B. holmesii has been isolated primarily from immunocompromised hosts (asplenic or sickle cell disease patients and transplant recipients) (14,17–20) and was first isolated from blood, the bacterium has also been found to cause respiratory diseases (11,12,21–23). B. holmesii was isolated from pleural fluid and lung biopsy specimens from an immunocompetent adolescent who had fever and pulmonary fibrosis (12) and from sputum of patients with respiratory failure (22). Moreover, B. holmesii was isolated from nasopharyngeal specimens of previously healthy persons who had whooping cough–like symptoms, including paroxysms, whooping, or post-tussive vomiting (11,21,23). Therefore, B. holmesii appears to be able to colonize the respiratory tract in the same manner as other Bordetella species. A case study in Japan also found epidemiologic links between 5 persons colonized with B. holmesii, which indicates the ability of this pathogen to transmit from person to person (6).
In collaboration with the Massachusetts Department of Public Health (MDPH), we reviewed B. holmesii surveillance data collected in Massachusetts during 2005–2009. B. holmesii was isolated from several patients experiencing whooping cough–like symptoms. By using a murine infection model, we examined the effects of B. pertussis vaccination on B. holmesii infection susceptibility.