Studies on the optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for preparation of a safe and potent pertussis vaccine

Gupta, Rajesh K.; Saxena, S.N.; Sharma, Suniti B.; Ahuja, Subhash

doi:10.1016/0264-410x(88)90099-0

Cited by 14 publications

(5 citation statements)

References 24 publications

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“…Various inactivating factors lyse B. pertussis cells with different intensities and decrease the opacity of bacteria suspension. These results are in agreement with other reports ( 19 , 28 ).…”

Section: Discussionsupporting

confidence: 94%

“…A test for agglutinins on bacterial suspensions 509 and 134 after inactivation under various conditions and pooled inactivated bacterial suspensions ( Table 3 ) showed inactivation conditions due to heat, formaldehyde, and glutaraldehyde not degraded agglutinins of both B. pertussis strains. There are other reports with similar findings to our results, showing that inactivated agents such as formaldehyde, glutaraldehyde, and heat do not destroy agglutinins of B. pertussis during the inactivation process ( 18 , 19 , 30 ). This work also revealed that thimerosal does not change agglutinins of B. pertussis during the inactivation conditions of F16 to F21.…”

Section: Discussionsupporting

confidence: 92%

“…On this basis, Gupta et al evaluated the effects of various chemical agents (such as glutaraldehyde, formaldehyde, acetone, and thimerosal) in different temperature conditions on the inactivation of B. pertussis cells ( 14 ). Moreover, some studies explained the preparation of a potent and safe pertussis vaccine with good stability using the glutaraldehyde inactivation process ( 15 - 19 ).…”

Section: Introductionmentioning

confidence: 99%

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Study on Toxicity Reduction and Potency Induction in Whole-cell Pertussis Vaccine by Developing a New Optimal Inactivation Condition Processed on Bordetella pertussis

Dounighi

Razzaghi-Abyane

Nofeli

et al. 2016

Jundishapur J Microbiol

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BackgroundWhooping cough is caused by Bordetella pertussis, and it remains a public health concern. Whole-cell pertussis vaccines have been commonly employed for expanded immunization. There is no doubt of the efficacy of whole cell pertussis vaccine, but it is necessary to improve the vaccine to decrease its toxicity.ObjectivesIn this study, an inactivation process of dealing with pertussis bacteria is optimized in order to decrease the bacteria content in human doses of vaccines and reduce the vaccine’s toxicity.Materials and MethodsThe bacterial suspensions of pertussis strains 509 and 134 were divided into 21 sample parts from F1 to F21 and inactivated under different conditions. The inactivated suspensions of both strains were tested for opacity, non-viability, agglutination, purity, and sterility; the same formulation samples that passed quality tests were then pooled together. The pool of inactivated suspensions were analyzed for sterility, agglutination, opacity, specific toxicity, and potency.ResultsThe harvest of both bacterial strains showed purity. The opacity of various samples were lost under different treatment conditions by heat from 8% to 12%, formaldehyde 6% to 8%, glutaraldehyde 6% to 8%, and thimerosal 5% to 8%. Tests on suspensions after inactivation and on pooled suspensions showed inactivation conditions not degraded agglutinins of both strains. The samples of F2, F4, F8, F12, F15, and F17 passed the toxicity test. The potency (ED50) of these samples showed following order F17 > F12 > F8 > F15, F4 > F2, and F17 revealed higher potency compared to other formulations.ConclusionsIt can be concluded that F17 showed desirable outcomes in the toxicity test and good immunogenicity with a low bacterial number content. Consequently, lower adverse effects and good immunogenicity are foreseeable for vaccine preparation with this method.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Study on Toxicity Reduction and Potency Induction in Whole-cell Pertussis Vaccine by Developing a New Optimal Inactivation Condition Processed on Bordetella pertussis

Dounighi

Razzaghi-Abyane

Nofeli

et al. 2016

Jundishapur J Microbiol

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“…dependent, but also the ADP-ribosyltransferase-independent biological activities of PTX. It is interesting that toxin molecuhs used in current acdluhr vaccine formulations are often inactivated by treatments with formaldehyde or glutaraldehyde (4,44), chemicals that primarily affect lysine residues in proteins. Since the $1 subunit does not contain lysines, the chemical treatment is likely to affect the B oligomer-specific activities.…”

Section: Immunogenicity Of Pt-re and Pt--renk It Was Interestingmentioning

confidence: 99%

Site-specific alterations in the B oligomer that affect receptor-binding activities and mitogenicity of pertussis toxin.

Lobet

Feron

Dequesne

et al. 1993

The Journal of Experimental Medicine

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SummaryPertussis toxin plays a major role in the pathogenesis of whooping cough and is considered an important constituent of vaccines against this disease. It is composed of five different subunits associated in a molar ratio 1S1:1S2:1S3:2S4:1S5. The $1 subunit is responsible for the ADPribosyltransferase activity of the toxin. The B moiety, composed of $2 through $5, recognizes and binds to the target cell receptors and has some ADP-ribosyltransferase-independent activities such as mitogenicity. Site-directed mutagenesis of subunits $2 and $3 allowed us to identify amino acid residues involved in receptor binding. Of all the modifications generated, the deletion of Ash 105 in $2 and of Lys 105 in $3 resulted in the more drastic reduction of binding to haptogiobin and CHO cells, respectively. A holotoxin carrying both deletions presented a mitogenicity reduced to an undetectable level. The combination of these B oligomer mutations with two substitutions in the $1 subunit led to the production of a toxin analog with reduced ADPoribosyltransferasedependent and -independent activities including mitogenicity. As shown by immunoprecipitation with various monodonal antibodies, the mutant holotoxin was correctly assembled and antigenically similar to the native toxin. This toxin analog induced toxin-neutralizing antibodies at the same level as the holotoxin carrying only mutations in the $1 subunit, and may therefore be considered a useful candidate for the development of a new generation vaccine against whooping cough.tel/a pertuss/s, the etiologic agent of whooping cough, duces a number of toxins responsible for the local and systemic manifestations of this important childhood disease (1). Among these toxins, pertussis toxin (PTX) 1 plays a major role in the pathogenesis, in that it expresses a wide variety of biological activities, such as histamine sensitization, activation of insulin secretion, promotion of lymphocytoffs, and others (2). In addition, immunization with PTX has been shown to protect mice against subsequent lethal challenge with virulent R pertuss/s (3). It is therefore considered an important constituent in vaccines against pertussis, and is the major component of the new acellnlar vaccines currently being tested or used in several countries (4,5).Paradoxically, this toxin may itself be responsible for the harmful side effects associated with the current vaccines (6). These side effects range in severity from minor local reactions and simple flushing, to permanent neurological damage t Abbre~aons used in this paper: CRAM, cross-reactive mutant; NAD, nicotinamide adenine dinudeotide; FTX, txn'tussis toxin; WT, wild type. and, in some rare cases, death. Before PTX can effectively and safely be used in pertussis vaccines, complete and irreversible detoxification is therefore required.The toxin is composed of five different subunits, named $1 to $5, based on their decreasing molecular weights. The subunits associate in a molar ratio of 1S1:1S2:1S3:2S4:1S5 to form the holotoxin. Functionally, FTX can be...

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“…In general, the rise in pertussis cases has led researchers to enhance pertussis surveillance efforts, biologically examine recent circulating Bp strains, and reevaluate current pertussis vaccination strategies as a means to gain insight in the reported case increase. In the US, acellular pertussis vaccines (DTaP) used consist of five Bp proteins, inactivated pertussis toxin (Ptx), filamentous hemagglutinin (FHA), pertactin (Prn), and fimbriae serotype 2 and/or 3 (Fim2/Fim3) which have been purified from the historic Bp strains, Tohama I (T) or 10536 [ 10 – 12 ]. Recently, studies focusing on pathogen adaptation have reported genetic differences between the current circulating Bp strains and vaccine strains [ 8 , 13 – 16 ] in genes encoding the five vaccine proteins.…”

Section: Introductionmentioning

confidence: 99%

A Proteomic Characterization of Bordetella pertussis Clinical Isolates Associated with a California State Pertussis Outbreak

Williamson

Moura

Whitmon

et al. 2015

International Journal of Proteomics

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Bordetella pertussis (Bp) is the etiologic agent of pertussis (whooping cough), a highly communicable infection. Although pertussis is vaccine preventable, in recent years there has been increased incidence, despite high vaccine coverage. Possible reasons for the rise in cases include the following: Bp strain adaptation, waning vaccine immunity, increased surveillance, and improved clinical diagnostics. A pertussis outbreak impacted California (USA) in 2010; children and preadolescents were the most affected but the burden of disease fell mainly on infants. To identify protein biomarkers associated with this pertussis outbreak, we report a whole cellular protein characterization of six Bp isolates plus the pertussis acellular vaccine strain Bp Tohama I (T), utilizing gel-free proteomics-based mass spectrometry (MS). MS/MS tryptic peptide detection and protein database searching combined with western blot analysis revealed three Bp isolates in this study had markedly reduced detection of pertactin (Prn), a subunit of pertussis acellular vaccines. Additionally, antibody affinity capture technologies were implemented using anti-Bp T rabbit polyclonal antisera and whole cellular proteins to identify putative immunogens. Proteome profiling could shed light on pathogenesis and potentially lay the foundation for reduced infection transmission strategies and improved clinical diagnostics.

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Studies on the optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for preparation of a safe and potent pertussis vaccine

Cited by 14 publications

References 24 publications

Study on Toxicity Reduction and Potency Induction in Whole-cell Pertussis Vaccine by Developing a New Optimal Inactivation Condition Processed on Bordetella pertussis

Study on Toxicity Reduction and Potency Induction in Whole-cell Pertussis Vaccine by Developing a New Optimal Inactivation Condition Processed on Bordetella pertussis

Site-specific alterations in the B oligomer that affect receptor-binding activities and mitogenicity of pertussis toxin.

A Proteomic Characterization of Bordetella pertussis Clinical Isolates Associated with a California State Pertussis Outbreak

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