Plague Vaccine Development: Current Research and Future Trends

Verma, Shailendra Kumar; Tuteja, Urmil

doi:10.3389/fimmu.2016.00602

Cited by 48 publications

(45 citation statements)

References 103 publications

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“… 15 , 17 – 19 A fusion of a monomerized form of F1 with another protective antigen LcrV, a pivotal component of the type III secretion system of Y. pestis , comprise the most promising anti-plague subunit vaccine that is under development. 20 – 25 The protective mechanism induced by F1 is based on the serological arm of adaptive immunity. 18 , 26 , 27 Passive transfer of anti-F1 antibodies to naive animals and generation of anti-F1 IgG titers following active immunization with F1 lead to high survival rates in animal models of plague.…”

Section: Introductionmentioning

confidence: 99%

Targeting of the Yersinia pestis F1 capsular antigen by innate-like B1b cells mediates a rapid protective response against bubonic plague

et al. 2018

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The generation of adaptive immunity by vaccination is usually a prolonged process that requires multiple dosing over several months. Hence, vaccines are administered for disease prevention a relatively long time prior to possible infection as opposed to post-exposure prophylaxis, which typically requires rapid intervention such as antibiotic therapy. The emergence of pathogens resistant to common antibiotic treatments has prompted the search for alternative therapeutic strategies. We previously demonstrated that vaccination of mice with the F1 capsular antigen of Yersinia pestis elicits specific and effective yet, unexpectedly, rapid anti-plague immunity. Here, we show by applying genetic and immunological approaches that the F1 antigen is targeted by peritoneal innate-like B1b cells that generate a prompt T-independent (TI) anti-F1 humoral response. The rapid F1-mediated defense response was diminished in Xid (Btkm) mice in which B1 cell numbers and activity are limited. Binding of fluorophore-labeled F1 to peritoneal B1b cells was detected as soon as 6 h post vaccination, emphasizing the high speed of this process. By assessing the ability to achieve rapid immunity with monomerized F1, we show that the natural polymeric structure of F1 is essential for (i) rapid association with peritoneal B1b cells, (ii) early induction of anti-F1 titers and (iii) rapid TI immunity in the mouse model of bubonic plague. These observations shed new light on the potential of novel as well as well-known protective antigens in generating rapid immunity and could be implemented in the rational design of future vaccines.

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Section: Introductionmentioning

confidence: 99%

Targeting of the Yersinia pestis F1 capsular antigen by innate-like B1b cells mediates a rapid protective response against bubonic plague

et al. 2018

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“…Vaccines against Y. pestis have been developed since the early identification of the pathogen and have saved many lives in Madagascar before antibiotics became widely available, but due to the significant side effects, local or systemic reactions that were sometimes serious, the need for revaccination and the plummeting of numbers of human cases, its use was abandoned. A number of candidates are currently under development 14. rF1V and SV1 vaccine candidates successfully passed phase II trials, and the WHO recently provided guidance for phase III evaluation in the field 15.…”

Section: Plague Vaccinesmentioning

confidence: 99%

Can we make human plague history? A call to action

et al. 2019

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“…Although these antibiotics are still used, resistance is emerging (Guiyoule et al 1997 , 2001 ; Hernandez et al 2003 ; Hinnebusch et al 2002 ). Besides, as currently no effective and licensed vaccine is available for the prevention of plague (Oyston and Williamson 2013 ; Verma and Tuteja 2016 ) alternative strategies to develop therapies against Yersinia related infections are needed.…”

Section: Introductionmentioning

confidence: 99%

LFchimera protects HeLa cells from invasion by Yersinia spp. in vitro

et al. 2018

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Yersinia pestis is the causative agent of plague. As adequate antibiotic treatment falls short and currently no effective vaccine is available, alternative therapeutic strategies are needed. In order to contribute to solving this problem we investigated the therapeutic potential of the peptide construct LFchimera against the safer-to-handle Y. pestis simulants Yersinia enterocolitica and Yersinia pseudotuberculosis in vitro. LFchimera is a heterodimeric peptide construct mimicking two antimicrobial domains of bovine lactoferrin, i.e. lactoferrampin and lactoferricin. LFchimera has been shown to be a potent antimicrobial peptide against a variety of bacteria in vitro and in vivo. Also Y. enterocolitica and Y. pseudotuberculosis have been shown to be susceptible for LFchimera in vitro. As Yersiniae spp. adhere to and invade host cells upon infection, we here investigated the effects of LFchimera on these processes. It was found that LFchimera has the capacity to inhibit host-cell invasion by Yersiniae spp. in vitro. This effect appeared to be host-cell mediated, not bacteria-mediated. Furthermore it was found that exposure of human HeLa epithelial cells to both LFchimera and the bacterial strains evoked a pro-inflammatory cytokine release from the cells in vitro.

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Plague Vaccine Development: Current Research and Future Trends

Cited by 48 publications

References 103 publications

Targeting of the Yersinia pestis F1 capsular antigen by innate-like B1b cells mediates a rapid protective response against bubonic plague

Targeting of the Yersinia pestis F1 capsular antigen by innate-like B1b cells mediates a rapid protective response against bubonic plague

Can we make human plague history? A call to action

LFchimera protects HeLa cells from invasion by Yersinia spp. in vitro

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