Protection against anthrax and plague by a combined vaccine in mice and rabbits

Ren, Jun; Dong, Dayong; Zhang, Jinlong; Zhang, Jun; Liu, Shilin; Li, Bing; Fu, Ling; Xu, Junjie; Yu, Changming; Hou, Lihua; Li, Jianmin; Chen, Wei

doi:10.1016/j.vaccine.2009.07.015

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…Y . pestis 141 (Sample ID: 11001) has a median lethal dose (MLD) of 17 colony-forming unit (CFU) when subcutaneously administered to BALB/c mice [17]. Y .…”

Section: Methodsmentioning

confidence: 99%

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Identification and characterization of a neutralizing monoclonal antibody that provides complete protection against Yersinia pestis

Liu¹,

Ren²,

Zhang³

et al. 2017

PLoS ONE

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Yersinia pestis (Y. pestis) has caused an alarming number of deaths throughout recorded human history, and novel prophylactics and therapeutics are necessary given its potential as a bioweapon. Only one monoclonal antibody has been identified to date that provides complete protection against Y. pestis. Here, we describe a second novel murine monoclonal antibody (F2H5) that provided complete protection against Y. pestis 141 infection when administered prophylactically to Balb/c mice (100 μg intravenously). We humanized F2H5, characterized its ability to bind to the Y. pestis F1 protein and further characterized the neutralizing epitope using computational and experimental approaches. While Western blot results suggested a linear epitope, peptide mapping using ELISA failed to identify an epitope, suggesting a conformational epitope instead. We adopted a computational approach based on Residue Contact Frequency to predict the site of antigen-antibody interaction and defined the F2H5/F1 binding site computationally. Based on computational approach, we determined that residues G104E105N106 in F1 were critical to F2H5 binding and that CDRH2 and CDRH3 of F2H5 interacted with F1. Our results show that combining computational approach and experimental approach can effectively identify epitopes.

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“…Y . pestis 141 (Sample ID: 11001) has a median lethal dose (MLD) of 17 colony-forming unit (CFU) when subcutaneously administered to BALB/c mice [17]. Y .…”

Section: Methodsmentioning

confidence: 99%

“…Expression and purification of recombinant F1 (rF1) has been described previously [17]. Briefly, the F1 gene was cloned into the expression vector pET-32a (+) to construct the final vector pET-F1, which was transformed into BL21(DE3) cells to obtain BL21(DE3)/pET-F1.…”

Section: Methodsmentioning

confidence: 99%

Identification and characterization of a neutralizing monoclonal antibody that provides complete protection against Yersinia pestis

Liu¹,

Ren²,

Zhang³

et al. 2017

PLoS ONE

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“…Recently, DNA vaccine that expressed both F1 and YscF (Yersinia secretory component F) antigens had shown to be protective . The protective antigen of Bacillus anthracis and the fraction 1 capsular antigen (F1 antigen) and V antigen of Y. pestis have been demonstrated to be potential candidate vaccine against anthrax and plague, respectively .…”

Section: Introductionmentioning

confidence: 99%

Multiple Antigen Peptide Containing B and T Cell Epitopes of F1 Antigen of Yersinia pestis Showed Enhanced Th1 Immune Response in Murine Model

et al. 2013

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Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Apart from humoral response, cell-mediated protection plays a major role in combating the disease. + showing Th1 response. Thus, the study highlights the importance of Th1 cytokine and existence of CD4 + and CD8 + immune response. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response.

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“…In previous reports on dual anthrax–plague vaccines, groups of animals were immunized with mixtures of PA, F1, and V (39–42) but challenged separately with either B. anthracis [intratracheal (39) or subcutaneous (40) administration of spores prepared from the non-encapsulated toxigenic Sterne strain] or Y. pestis [intraperitoneal (39) or subcutaneous (40–42) injection]. However, this model would not provide an accurate assessment of dual protection because the animals were not exposed to both the agents.…”

Section: Resultsmentioning

confidence: 99%

A Bivalent Anthrax–Plague Vaccine That Can Protect against Two Tier-1 Bioterror Pathogens, Bacillus anthracis and Yersinia pestis

et al. 2017

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Bioterrorism remains as one of the biggest challenges to global security and public health. Since the deadly anthrax attacks of 2001 in the United States, Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, gained notoriety and were listed by the CDC as Tier-1 biothreat agents. Currently, there is no Food and Drug Administration-approved vaccine against either of these threats for mass vaccination to protect general public, let alone a bivalent vaccine. Here, we report the development of a single recombinant vaccine, a triple antigen consisting of all three target antigens, F1 and V from Y. pestis and PA from B. anthracis, in a structurally stable context. Properly folded and soluble, the triple antigen retained the functional and immunogenicity properties of all three antigens. Remarkably, two doses of this immunogen adjuvanted with Alhydrogel® elicited robust antibody responses in mice, rats, and rabbits and conferred complete protection against inhalational anthrax and pneumonic plague. No significant antigenic interference was observed. Furthermore, we report, for the first time, complete protection of animals against simultaneous challenge with Y. pestis and the lethal toxin of B. anthracis, demonstrating that a single biodefense vaccine can protect against a bioterror attack with weaponized B. anthracis and/or Y. pestis. This bivalent anthrax–plague vaccine is, therefore, a strong candidate for stockpiling, after demonstration of its safety and immunogenicity in human clinical trials, as part of national preparedness against two of the deadliest bioterror threats.

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Protection against anthrax and plague by a combined vaccine in mice and rabbits

Cited by 12 publications

References 38 publications

Identification and characterization of a neutralizing monoclonal antibody that provides complete protection against Yersinia pestis

Identification and characterization of a neutralizing monoclonal antibody that provides complete protection against Yersinia pestis

Multiple Antigen Peptide Containing B and T Cell Epitopes of F1 Antigen of Yersinia pestis Showed Enhanced Th1 Immune Response in Murine Model

A Bivalent Anthrax–Plague Vaccine That Can Protect against Two Tier-1 Bioterror Pathogens, Bacillus anthracis and Yersinia pestis

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