Effect of Acellular Pertussis Vaccine Against Various Strains of Bordetella Pertussis in a Murine Model of Respiratory Infection.

Watanabe, Mineo; Nagai, Masaaki

doi:10.1248/jhs.48.560

Cited by 9 publications

(6 citation statements)

References 16 publications

(14 reference statements)

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“…Taking together, based on our results and those on vaccinated mice previously published [9] , [10] , [11] , [12] , [13] we propose that of the three Prn variants, Prn1 binds most efficiently to the host cells, explaining its predominance in unvaccinated populations. Vaccination with Prn1-containing vaccines may have shifted the competitive balance between Prn variants allowing non-vaccine types Prn2 and Prn3 to emerge.…”

Section: Discussionsupporting

confidence: 76%

“…Antigenic divergence has occurred between vaccine strains and clinical isolates with respect to several vaccine components; Ptx, Prn, and fimbriae [3] , [6] , [7] , [8] . Further variation in Ptx and Prn has been shown to affect vaccine efficacy in a mouse model [9] , [10] , [11] , [12] , [13] . In addition to antigenic variation, increased Ptx production has been associated with the resurgence of pertussis [14] .…”

Section: Introductionmentioning

confidence: 99%

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Studies on Prn Variation in the Mouse Model and Comparison with Epidemiological Data

Gent¹,

Loo

Heuvelman³

et al. 2011

PLoS ONE

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The virulence factor pertactin (Prn) is a component of pertussis vaccines and one of the most polymorphic Bordetella pertussis antigens. After the introduction of vaccination shifts in predominant Prn types were observed and strains with the Prn vaccine type (Prn1) were replaced by strains carrying non-vaccine types (Prn2 and Prn3), suggesting vaccine-driven selection. The aim of this study was to elucidate the shifts observed in Prn variants. We show that, although Prn2 and Prn3 circulated in similar frequencies in the 1970s and 1980s, in the 1990s Prn2 strains expanded and Prn3 strains disappeared, suggesting that in vaccinated populations Prn2 strains are fitter than Prn3 strains. We established a role for Prn in the mouse model by showing that a Prn knock-out (Prn-ko) mutation reduced colonization in trachea and lungs. Restoration of the mutation resulted in a significant increase in colonization compared to the knock-out mutant. The ability of clinical isolates with different Prn variants to colonize the mouse lung was compared. Although these isolates were also polymorphic at other loci, only variation in the promoter for pertussis toxin (ptxP) and Prn were found to contribute significantly to differences in colonization. Analysis of a subset of strains with the same ptxP allele revealed that the ability to colonize mice decreased in the order Prn1>Prn2 and Prn3. Our results are consistent with the predominance of Prn1 strains in unvaccinated populations. Our results show that ability to colonize mice is practically the same for Prn2 and Prn3. Therefore other factors may have contributed to the predominance of Prn2 in vaccinated populations. The mouse model may be useful to assess and predict changes in the B. pertussis population due to vaccination.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Studies on Prn Variation in the Mouse Model and Comparison with Epidemiological Data

Gent¹,

Loo

Heuvelman³

et al. 2011

PLoS ONE

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“…Thus variation in these proteins may affect immune recognition and hence strain fitness. Significantly, antigenic divergence has been observed between circulating strains and vaccine strains with respect to these five proteins and several studies in mouse models have provided evidence this affects vaccine efficacy [33] , [34] , [35] , [36] , [37] . Besides antigenic divergence between circulating strains and vaccine strains, another adaptive phenomenon may be the recent emergence of strains with increased Ptx production [5] , [26] , [38] , [39] .…”

Section: Introductionmentioning

confidence: 99%

Small Mutations in Bordetella pertussis Are Associated with Selective Sweeps

et al. 2012

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Bordetella pertussis is the causative agent of pertussis, a highly contagious disease of the human respiratory tract. Despite high vaccination coverage, pertussis has resurged and has become one of the most prevalent vaccine-preventable diseases in developed countries. We have proposed that both waning immunity and pathogen adaptation have contributed to the persistence and resurgence of pertussis. Allelic variation has been found in virulence-associated genes coding for the pertussis toxin A subunit (ptxA), pertactin (prn), serotype 2 fimbriae (fim2), serotype 3 fimbriae (fim3) and the promoter for pertussis toxin (ptxP). In this study, we investigated how more than 60 years of vaccination has affected the Dutch B. pertussis population by combining data from phylogeny, genomics and temporal trends in strain frequencies. Our main focus was on the ptxA, prn, fim3 and ptxP genes. However, we also compared the genomes of 11 Dutch strains belonging to successful lineages. Our results showed that, between 1949 and 2010, the Dutch B. pertussis population has undergone as least four selective sweeps that were associated with small mutations in ptxA, prn, fim3 and ptxP. Phylogenetic analysis revealed a stepwise adaptation in which mutations accumulated clonally. Genomic analysis revealed a number of additional mutations which may have a contributed to the selective sweeps. Five large deletions were identified which were fixed in the pathogen population. However, only one was linked to a selective sweep. No evidence was found for a role of gene acquisition in pathogen adaptation. Our results suggest that the B. pertussis gene repertoire is already well adapted to its current niche and required only fine tuning to persist in the face of vaccination. Further, this work shows that small mutations, even single SNPs, can drive large changes in the populations of bacterial pathogens within a time span of six to 19 years.

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“…However, it has also been proposed that reemergence may be due to antigenic shift in the circulating strains in response to pertussis vaccines. Previous studies (11,23,31,35) reported that polymorphisms of the pertussis toxin A subunit (PtxA) and pertactin (Prn) in circulating B. pertussis strains in the Netherlands distinguished these proteins from those present in the pertussis vaccine (8,30), and these polymorphisms have now been detected worldwide (1,3,4,6,8,12,19,26,30). Since these two proteins have been shown to be protective antigens of B. pertussis and are used as essential components of acellular pertussis vaccines, it has been proposed that the polymorphisms may confer vaccine resistance and contribute to reemergence.…”

mentioning

confidence: 96%

Synergic Effect of Genotype Changes in Pertussis Toxin and Pertactin on Adaptation to an Acellular Pertussis Vaccine in the Murine Intranasal Challenge Model

Komatsu

Yamaguchi

Abe

et al. 2010

Clin Vaccine Immunol

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The Bordetella pertussis pertussis toxin and pertactin (Prn) are protective antigens and are contained in acellular pertussis vaccines. Polymorphisms in the A subunit of pertussis toxin (PtxA) and pertactin have been proposed to mediate vaccine resistance and contribute to pertussis reemergence. To test this hypothesis, previous studies compared clinical isolates expressing different alleles for the proteins. However, other virulence factors or virulence factor expression levels also may vary, confounding the analysis. To overcome these limitations, we constructed isogenic mutants of B. pertussis Tohama expressing the alleles ptxA1 or ptxA2 and prn1 or prn2 and compared the efficacies of an acellular pertussis vaccine against the mutants in a mouse model. While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains. These results suggest that an allele shift to the ptxA1 prn2 genotype may play a role in the emergence of pertussis in vaccinated populations.

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Effect of Acellular Pertussis Vaccine Against Various Strains of Bordetella Pertussis in a Murine Model of Respiratory Infection.

Cited by 9 publications

References 16 publications

Studies on Prn Variation in the Mouse Model and Comparison with Epidemiological Data

Studies on Prn Variation in the Mouse Model and Comparison with Epidemiological Data

Small Mutations in Bordetella pertussis Are Associated with Selective Sweeps

Synergic Effect of Genotype Changes in Pertussis Toxin and Pertactin on Adaptation to an Acellular Pertussis Vaccine in the Murine Intranasal Challenge Model

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