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Bordetella Pertussis Protects Against Severe Influenza

Introduction

The article did not give us a summary of discusses protection against influenza virus pathogenesis by pre-exposure to attenuated Bordetella pertussis. The authors rather introduce us to the history of virulent influenza which should have been dealt in the introduction page. The abstract also lacks an in-depth analysis on the attenuated Bordetella pertussis subject, and hence can not help a reader to ascertain the paper’s purpose. In another statement Rui et al (2010) state that “Mass vaccination remains the most effective way to combat influenza” (p.1). Here the article takes us back to the previous pathogenic studies that should have been mentioned in the literature review. In another analysis, Rui et al (2010) add that “however, current vaccination strategies face the challenge to meet the demands in a pandemic situation” (p.2). Again, the statement sounds like a conclusive analysis and does not succinctly communicate complex research ideas. In summary, an abstract should act as a patent application, where research ideas are first introduced to the reader (Wirsing 200; Tan & Skowronski 10).

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Experimental Design

The information-gathering exercise did not present any variables to be measured at the end of the study. The article however did not indicate whether the study design was a controlled experiment, randomized experiments, statistical survey, natural experiment, or even an observed study. The experimental units presented here did not explain how participants were chosen.

Methods and Techniques

Research methodology did not indicate where blood samples were collected from and if any of the participants were indeed suffering from attenuated Bordetella pertussis (Weiss 37). It is evidenced that virulent influenza can have adverse effects on a person’s life which could affect family and social life. Numerous studies in human and animal models have suggested that performing a test on the neonatal immune system in a mouse model is immature to effectively induce vaccine-mediated protective immunity (Wirsing et al 199; Siegrist 3332). Especially in severely influenza-induced pneumonitis, the production of Bordetella pertussis (BPZE1) response is essential to the development of the protective immunity to pertussis (Mills 1018). This is also reflected by the fact that significant amounts of BPZE1 specific are only produced after several months of vaccine-induced immunity with pertussis vaccines and can not protect the body during epidemics (Lu et al 5903).

Several studies have demonstrated the effectiveness of B. pertussis in inducing strong and long-lasting immunity as compared to vaccine-induced immunity (Wirsing et al 200). Furthermore, infections with B. pertussis induce measurable antigen-specific…these observations suggest that live vaccination administered through nasal route closely mimic natural B. pertussis and maybe the best alternatives over the currently available vaccines. There are currently many vaccination compositions to treat Bordetella infection but the immunogenic composition is not effective in treating influenza in human beings, or in cases where epidemic or rapid protective immunity is required (Wirsing 1326; Mielcarek 65).

Various types of vaccinating compositions mentioned in this article fail to address the problem of providing a vaccine or even an immunogenic composition that protects emergencies or even prior protection to newborn babies before they are of the age of six months. It is also evidenced that the production of immunogenic composition through genetic attenuation of a Bordetella strain such as B. pertussis diminishes pathogenicity while maintaining the ability to control and induce protective immunity. Here, the study fails to present inventions that would produce vaccines that induce protection after a single intranasal administration that is more superior to the protection provided by the current B. pertussis. This is yet another invention that should protect against infection with Bordetella pertussis, which was not seen after vaccine-induced immunity injection (Rui 2).

Rui and his colleagues’ article on B. Pertussis protection against severe influenza should present inventions that induce strong protective immunity against Bordetella infection and provide a vaccine composition that induces mucosal and systematic immunity. In another study, the present invention that induces a live attenuated Bordetella pertussis strain was given a single-dose nasal vaccine called BPZE1. Here Rui Li et al (2) argue that the BPZE1 vaccine can not only be used to vaccinate newborns but can be used to vaccinate mammals of any age in case of an epidemic. Rui et al (2010) article also state “BPZE1-treated animals displayed markedly reduced lung inflammation and tissue damage, decreased neutrophil infiltration, and strong suppression of the production of major-inflammatory mediators in their bronco-alveolar fluids” (p.2). Again, the research did not indicate any measurable device used to ascertain the validity of the results obtained. The data obtained to evidence remarkable improvement in lung inflammation are purely theoretical. With this regard, the research article and the outlined evidence are of no value and are viable for present application in fighting influenza.

Data Analysis

As evidenced from a summary of inventions, descriptions of preferred B. pertussis vaccines, and claims, the present inventions provide a deleted Bordetella strain. This research also provides methods of protecting mammals against diseases caused by Bordetella strain pertussis comprising administering to said mammals in need of deleted gene.

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Results and Methods

Construction of B. Pertussis BPZE1 that targeted three virulence factors; TCT, PTX, and DNT should have been analyzed using an unpaired Student’s t-test and the Kruskal-Wallis test followed by Dunn’s post-test and the differences measured at a certain variable scale to test the validity of the results. TCT is responsible for destructing ciliated cells in the trachea of the infected hosts (Heiss et al 177; Goldman & Cookson 187) involved in the influenza pathogens. Rui et al (5) also state that tracheal cytotoxins are generally broken down B. products of peptidoglycan in the cell wall of Gram-negative bacteria (Cookson et al 2224). Here, B. pertussis amp alone is inefficient in breaking down peptidoglycan products. This requires the replacement of β pertussis AmpG with E. coli amps which would produce a strain of less than 1% residual TCT activity, an analysis that was overlooked in the research (Loch 130).

PTX is evidenced to be a major virulence factor in performing systematic effects of B. pertussis composed of enzymatic active moiety known as the S1, responsible for binding target cell receptors and one of the major important protective agents that inactivate toxins. Here, Lotch (1999) states that “research on Allelic exchange should be first performed by deleting the ptx operon and inserting a mutated version” (p.130). It evidenced that Allelic exchange removes the dnt gene although the role of DNT in the virulence of B. Pertussis is not certain as it has been identified as an important toxin.

In vitro studies of B. Pertussis BPZE1, Lotch (1999) evidences that the genetic alterations in BPZE1 are evidenced to affect the bacterial cell wall synthesis in terms of size and growth as well as the vitro growth rate at BPZE1. However, when compared with the parental strain BPSM, the studies did not show any differences between BPZE1 and BPZE1 in bacterial shape and size as evidenced by microscopic analysis. This comparison was important in determining whether the absence of alterations in the targeted toxins affect adherence properties of S. pertussis and the attachment rates of BPZE1 and BPSM using human pulmonary epithelial cells (131).

Here, the study did not also show significant differences in the adherence capabilities of either cell.

Attenuation of B. Pertussis BPZE1

The study where Balb/C mice were constantly infected with BPZE1 and colonization monitored over some time showed BPZE1 did manage to colonize in the lungs of mice although the results consistently lacked evidence to back this analysis. Also, studies with strains deleted genes did not provide data to support this analysis. Rui et al (2010) findings further state that

where lungs were examined for histological changes, inflammatory cell recruitment of 7 days after infection were reported to be associated with strong hypertrophy of the bronchiolar epithelial cells in (BPSM) and no changes were recorded in BPZE1-infected animals as the histology of the BPZE1 of infected mice that have received PBS instead of the bacteria. The B. Pertussis-induced inflammation was monitored for two months and the results indicated that the mutations introduced into BPZE1 resulted in drastic attenuation, but allowed bacteria to colonize in the lung (5).

Statistical Analysis

The BPZE1 challenge infection did not provide any figures of the bacteria that remained in the aPV animals. Also, Watanabe (2004) stated that “the difference between the BPZE1 and the PV vaccinated mice bacterial load did not indicate any statistical significance in the mouse model intranasal administration” (999). The frequency of infected population with (Watanabe 999) attenuated Bordetella pertussis are largely underestimated since the infections have been increasing over the last decades possibly because pertussis vaccines have been known to provide low or completely no protection against B. pertussis. The study did not introduce controls to be used in the study hence making conclusions drawn from the experiments unreliable and inconclusive. Additionally, data analysis using statistics figures also interpreted the results unconvincing.

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Conclusion and Discussion

The mechanisms of protective immunity against B. Pertussis do not prove a clear conclusive analysis we can base our future research on. This is demonstrated in unclear evidence of the role of B cells and IFN-γ demonstrated in the mouse (Mills 594). Many features of the model system employed by the study can not be considered relevant. The virus used to infect the animals is a mouse-adapted strain of the human H1N1 virus and has not been carefully analyzed in previous studies. The research in BPZE 1 also evidences that vaccine-induced immunity with pertussis vaccines and can protect the body during epidemics, but there are relatively high production costs associated with treatment. The study also demonstrated evidence of Bordetella strains and growth conditions but Ag-induced IFN γ secretion did not correlate with the duration of the bacterial growth and the age of the infected mouse. The B. pertussis used in the study was derived from B. Pertussis BPSM (Menozzi et al 1138) provided by Dr. N. Guiso that induces significant respiratory pathology contrary to previous investigations that have dwelt entirely on utilizing strains. Although a mouse model for the evaluation of pathogenesis and immunity to influenza sheds light on the possible underlying pathology responsible for driving the illness against severe influenza, it is important to note that the basis for susceptibility to the condition is multifactorial, and is likely to be significantly influenced by both, the viral strain as well as the pathogenic bacterial used in the study.

Works Cited

Cookson Belser, Cho H-L, Herwaldt, Goldman, Wilber. Biological activities and chemical composition of purified tracheal cytotoxin of Bordetella pertussis. Infect Immun. 57 (1989) :2223–2229

Goldman, Walsh., Cookson, Belser. “Structure and functions of the Bordetella tracheal cytotoxin”. Journal of Exp Clin Med. Suppl 13 (1988): 187-191.

Heiss, Flak., Lancaster, McDaniel., & Goldman, Wilber. “Nitric oxide mediates Bordetella pertussis tracheal cytotoxin damage to the respiratory epithelium”. Infect Agents Dis 2 (1993): 173-177

Locht, Camille., & Antoine, Rooijen. “Bordetella pertussis protein toxins”. Academic Press 5 (1999):130-146

Lu, Xue., Tumpey,Telugaukula., Morken, Zaki, Cox, Natalie., & Katz. Martin. “A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans”. J. Virol. 73 (1999):5903–5911.

Menozzi. Farrar., Mutombo, Renauld., Renauld, Garigliany., & Gantiez, Camelline “Heparin-inhibitable lectin activity of the filamentous hemagglutinin adhesin of Bordetella pertussis”. Infect lmmun 62 (1994): 769-778. 14.

Mills, Higgins.Immunity to Bordetella pertussis”. Microbes Infect 3 (2001): 655-677.

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Mills, Higgins., Ryan Mielcarek., & Ryan, Mahon. “A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis”. Infect lmmun 66 (1998): 594-602.

Mielcarek, Nathalie., Debrie, Sophie., Raze, Dominique., Bertout, Julie., Carine Rouanet, Amena Ben Younes, Colette Creusy, Jacquelyn Engle, Goldman, William., & Camille, Locht. “Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough”. LoS Pathog. 2(7) (2006): 65.

Rui Li., Annabelle Lim., Meng Chee Phoon., Teluguakula Narasaraju.,Jowin, Peng Poh, Meng, Kwoon., Vincent , Chow., Camille Locht., & Sylvie Alonso. “Attenuated Bordetella pertussis protects against highly pathogenic influenza A viruses by dampening the cytokine storm”. American Society for Microbiology 5 (2010): 1-43

Siegrist ,Carine. “Neonatal and early life vaccinology”. Vaccine 19 (2001): 3331-33

Tan, Trindade., & Skowronski, Dowsky. “Epidemiology of Pertussis”. Pediatr Infect Dis J 24 (2005): S10-S18

Watanabe, Meng., Nagai, Mills. “Whooping cough due to Bordetella parapertussis: an unresolved problem”. Expert Rev Anti Infect Ther 2 (2004): 447-454.

Weiss & Goodman. “Lethal infection by Bordetella pertussis mutants in the infant mouse model”. Infect. Immun. 57 (1989): 3757-3764.

Wirsing von, Kόnig., Halperin, Riffelmann., & Mills, Guiso. “Pertussis of adults and infants”. Lancet Infect Dis 2 (2002): 744-750.

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StudyCorgi. (2022, March 11). Bordetella Pertussis Protects Against Severe Influenza. Retrieved from https://studycorgi.com/bordetella-pertussis-protects-against-severe-influenza/

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StudyCorgi. (2022, March 11). Bordetella Pertussis Protects Against Severe Influenza. https://studycorgi.com/bordetella-pertussis-protects-against-severe-influenza/

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