Current challenges in the development of vaccines for pneumonic plague

Smiley, Stephen T.

doi:10.1586/14760584.7.2.209

Cited by 141 publications

(202 citation statements)

References 112 publications

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“…Human pathogens that reside within host cells and, like Chlamydia, induce natural immunity after infection include bacteria such as Salmonella, Shigella, Mycobacterium, and Yersinia, and parasites such as Leishmania (3,31,(48)(49)(50). Because immunity against these pathogens appears to be mediated by cellular and antibody responses, the approach described here could lead to the discovery of vaccines that have so far proved to be difficult to develop.…”

Section: Discussionmentioning

confidence: 99%

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Finco

Frigimelica

Buricchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Natural immunity against obligate and/or facultative intracellular pathogens is usually mediated by both humoral and cellular immunity. The identification of those antigens stimulating both arms of the immune system is instrumental for vaccine discovery. Although high-throughput technologies have been applied for the discovery of antibody-inducing antigens, few examples of their application for T-cell antigens have been reported. We describe how the compilation of the immunome, here defined as the pool of immunogenic antigens inducing T- and B-cell responses in vivo, can lead to vaccine candidates against Chlamydia trachomatis . We selected 120 C. trachomatis proteins and assessed their immunogenicity using two parallel high-throughput approaches. Protein arrays were generated and screened with sera from C. trachomatis -infected patients to identify antibody-inducing antigens. Splenocytes from C. trachomatis -infected mice were stimulated with 79 proteins, and the frequency of antigen-specific CD4 + /IFN-γ + T cells was analyzed by flow cytometry. We identified 21 antibody-inducing antigens, 16 CD4 + /IFN-γ + –inducing antigens, and five antigens eliciting both types of responses. Assessment of their protective activity in a mouse model of Chlamydia muridarum lung infection led to the identification of seven antigens conferring partial protection when administered with LTK63/CpG adjuvant. Protection was largely the result of cellular immunity as assessed by CD4 + T-cell depletion. The seven antigens provided robust additive protection when combined in four-antigen combinations. This study paves the way for the development of an effective anti- Chlamydia vaccine and provides a general approach for the discovery of vaccines against other intracellular pathogens.

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Section: Discussionmentioning

confidence: 99%

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Finco

Frigimelica

Buricchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…20 In addition, subunit vaccines based on F1 and LcrV antigens failed to fully protect African green monkeys, and the adequate evidence about whether or not they will protect humans has yet to be demonstrated. 21,22 Our previous study 23 and several reports 7,24,25 have indicated that subunit vaccines in alhydrogel elicit robust humoral immunity, and their potential to prime effective cellular immunity has yet to be demonstrated. Several studies suggest that antibodies alone may not provide optimal protection against plague, and that vaccines harnessing both humoral and cellular defense mechanisms should provide superior defense.…”

Section: Introductionmentioning

confidence: 98%

Yersinia pestisbiovarMicrotusstrain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques

Zhang

Wang

Guang

et al. 2013

Human Vaccines & Immunotherapeutics

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“…19 It has been suggested that both helper T lymphocyte responses of the Th1 type that govern immune cellular interactions and Th2 responses that give rise to antibody production are needed for optimal vaccine protection as a result of the concept in plague that early intracellular bacterial growth in macrophages, where bacteria survive by inhibiting nitric oxide in phagosomes and when a Th1 response would be relevant, and a subsequent extracellular growth of bacteria, when the Th2 response would drive antibody-dependent defense, are both essential for plague pathogenesis. 48,49 It is anticipated that a vaccine will be available in the next decade and will be useful for military exposure on a battlefield, first responders to bioterrorist use, laboratory workers, and travelers to endemic regions of the world.…”

Section: Vaccinesmentioning

confidence: 99%

Plague Gives Surprises in the First Decade of the 21st Century in the United States and Worldwide

Butler¹

2013

The American Society of Tropical Medicine and Hygiene

112

105

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Abstract. Plague is an ancient disease caused by the bacterium Yersinia pestis and transmitted by rodent flea bites that continues to surprise us with first-ever events. This review documents plague in human cases in the 1st decade of the 21st century and updates our knowledge of clinical manifestations, transmission during outbreaks, diagnostic testing, antimicrobial treatment, and vaccine development. In the United States, 57 persons were reported to have the disease, of which seven died. Worldwide, 21,725 persons were affected with 1,612 deaths, for a case-fatality rate of 7.4%. The Congo reported more cases than any other country, including two large outbreaks of pneumonic plague, surpassing Madagascar, which had the most cases in the previous decade. Two United States scientists suffered fatal accidental exposures: a wildlife biologist, who carried out an autopsy on a mountain lion in Arizona in 2007, and a geneticist with subclinical hemochromatosis in Chicago, who was handling an avirulent strain of Y. pestis in 2009. Antimicrobial drugs given early after the onset of symptoms prevented many deaths; those recommended for treatment and prophylaxis included gentamicin, doxycycline, and fluoroquinolones, although fluoroquinolones have not been adequately tested in humans. Fleas that do not have their guts blocked by clotted blood meals were shown to be better transmitters of plague than blocked fleas. Under development for protection against bioterrorist use, a subunit vaccine containing F1 and V antigens of Y. pestis was administered to human volunteers eliciting antibodies without any serious side effects. These events, although showing progress, suggest that plague will persist in rodent reservoirs mostly in African countries burdened by poverty and civil unrest, causing death when patients fail to receive prompt antimicrobial treatment.

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Current challenges in the development of vaccines for pneumonic plague

Cited by 141 publications

References 112 publications

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Yersinia pestisbiovarMicrotusstrain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques

Plague Gives Surprises in the First Decade of the 21st Century in the United States and Worldwide

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