Development of vaccines against pertussis caused by Bordetella holmesii using a mouse intranasal challenge model

Abstract

Bordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii-specific serum antibodies might play an important role in protection. Immuno-proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipAlike protein of B. holmesii. An aBH vaccine prepared from a BipA-like protein-deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipAlike protein plays an important role in the protective efficacy of aBH vaccine.Key words BipA-like protein, Bordetella holmesii, pertussis, whooping cough.Pertussis (whooping cough) is a highly contagious respiratory disease caused, in most cases, by Bordetella pertussis. Introduction of effective pertussis vaccines has dramatically reduced the incidence of pertussis caused by B. pertussis worldwide (1). However, current pertussis vaccines are not effective against other causative agents of pertussis, such as B. parapertussis and B. holmesii (2-5). Our previous studies showed that effective vaccines against B. parapertussis can be prepared from formalin-inactivated whole cells or FHA of B. parapertussis (3). The goal of the present study was to develop effective vaccines against respiratory infection by B. holmesii.Bordetella holmesii was first reported in 1995 after isolation from a patient with sepsis, and it is recognized as a causative agent of systemic infection, mainly in immunocompromised hosts (6). During the past decade, B. holmesii has also been isolated from patients with pertussis-like symptoms (7,8). Recent epidemiological studies suggest that pertussis caused by B. holmesii List of Abbreviations: 2D PAGE, two dimensional polyacrylamide gel electrophores; aBH, acellular vaccine prepared from Bordetella holmesii; BG agar, Bordet-Gengou agar; BH2Sm r -4BipA, BipA-like protein deficient-mutant of B. holmesii; CFU, colony-forming units; CasS/S, Stainer Scholte medium supplemented with 0.25 (w/v) Casamino acids; DPBS, Dulbecco's modified phosphate-buffered saline (À) pH 7.4; DTT, dithiothreitol; DTaP, diphtheriatetanus acellular pertussis vaccine; FHA, filamentous hemagglutinin; FIM, fimbriae; HE, hematoxylin-eosin; Incubation buffer, washing buffer containing 10% (w/v) skimmed milk; PFGE, pulse field gel electrophoresis; PRN, ...

Conserved Patterns of Symmetric Inversion in the Genome Evolution of Bordetella Respiratory Pathogens

“…Although B. pertussis is the primary agent, B. parapertussis also causes clinical whooping cough (18,28,56), and increasing reports have attributed pertussis-like cough illness to B. holmesii (19)(20)(21)(22). Current acellular pertussis vaccines contain immunogenic proteins purified from B. pertussis and provide no cross-protection against B. holmesii (57,58) and debated protection against B. parapertussis (59)(60)(61)(62)(63)(64)(65)(66). However, widespread application of acellular pertussis vaccines may have influenced the circulating population structure of all three species (19,29,67,68).…”

Bordetella holmesii Lipopolysaccharide Hide and Seek Game with Pertussis: Structural Analysis of the O-Specific Polysaccharide and the Core Oligosaccharide of the Type Strain ATCC 51541

“…The relation between B. pertussis and B. holmesii infections remains unknown, but cases of the co-infection have been reported recently. More importantly, there is no effective vaccine against B. holmesii, and the existing pertussis DTwP and DTaP vaccines do not provide cross-protection in animal models of B. holmesii infection [ 15 , 29 ]. Thus, it is vital to distinguish B. pertussis and B. holmesii infections efficiently as failing to do so may substantially underestimate the efficiency of anti-pertussis vaccination.…”

“…The relation between B. pertussis and B. holmesii infections remains unknown. To date there is no effective vaccine against B. holmesii, and the existing pertussis DTwP and DTaP vaccines do not provide cross-protection in animal models of B. holmesii infection [ 15 , 29 ]. Lipopolysaccharide is one of the common virulence factors and the essential constituent of the bacterial membrane of all Bordetellae [ 16 ].…”

Krztusiec I „Efekt Czerwonej Królowej”

“…Globalnie dostępne bezkomórkowe szczepionki przeciwkrztuścowe nie zapewniają ochrony przeciwko B. holmesii. Pałeczki B. holmesii nie wytwarzają PT, FHA, PRN i FIM, które są antygenami szczepionkowymi obecnymi w szczepionce DTaP [64]. Poliklonalne przeciwciała indukowane szczepionką DTaP, rozpoznają tylko jeden nieokreślony antygen z niską efektywnością, a przeciwciała indukowane szczepionką pełnokomórkową DTwP rozpoznają jedynie antygeny o masie niższej niż 60 kDa [97].…”