Small protective fragments of the Yersinia pestis V antigen

Vernazza, Claire; Lingard, Bry; Flick-Smith, Helen C.; Baillie, Les; Hill, Jim; Atkins, Helen S.

doi:10.1016/j.vaccine.2009.03.011

Cited by 24 publications

(22 citation statements)

References 26 publications

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“…Three monoclonal antibodies (MAbs) have been independently cloned that can protect mice from bubonic and pneumonic plague (2,27,48). Although it is unclear whether each of these targets the same epitope, deletion studies of LcrV antigen suggest multiple protective epitopes exist (13,39,44,51).…”

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confidence: 99%

Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague

Eisele

Anderson²

2009

Clin Vaccine Immunol

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Yersinia pestis causes pneumonic plague, a necrotic pneumonia that rapidly progresses to death without early treatment. Antibodies to the protective antigen LcrV are thought to neutralize its essential function in the type III secretion system (TTSS) and by themselves are capable of inducing immunity to plague in mouse models. To develop multivalent LcrV antibodies as a therapeutic treatment option, we screened for monoclonal antibodies (MAbs) to LcrV that could prevent its function in the TTSS. Although we were able to identify single and combination MAbs that provided the high-level inhibition of the TTSS, these did not promote phagocytosis in vitro and were only weakly protective in a mouse pneumonic plague model. Only one MAb, BA5, was able to protect mice from pneumonic plague. In vitro, MAb BA5 blocked the TTSS with efficiency equal to or even less than that of other MAbs as single agents or as combinations, but its activity led to increased phagocytic uptake. Polyclonal anti-LcrV was superior to BA5 in promoting phagocytosis and also was more efficient in protecting mice from pneumonic plague. Taken together, the data support a hypothesis whereby the pulmonary clearance of Y. pestis by antibodies requires both the neutralization of the TTSS and the simultaneous stimulation of innate signaling pathways used by phagocytic cells to destroy pathogens.

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confidence: 99%

Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague

Eisele

Anderson²

2009

Clin Vaccine Immunol

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“…The LcrV/F1-based DNA vaccines were developed as an alternative approach to protein-based vaccines that contain either full or part of the open reading frames encoding LcrV, F1, or both. A peptide (127-amino acid) vaccine of LcrV antigen elicited a strong humoral immune response and provided 60% protection against Y. pestis in mice (68). The addition of the constructs of molecular immunopotentiator IL-12 with F1 or LcrV has significantly enhanced the immune response and showed 80% protection from a subsequent inhalational challenge with Y. pestis (69).…”

Section: Dna Vaccines Strategiesmentioning

confidence: 99%

Plague Vaccine Development: Current Research and Future Trends

Verma

Tuteja

2016

Front. Immunol.

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Plague is one of the world’s most lethal human diseases caused by Yersinia pestis, a Gram-negative bacterium. Despite overwhelming studies for many years worldwide, there is no safe and effective vaccine against this fatal disease. Inhalation of Y. pestis bacilli causes pneumonic plague, a fast growing and deadly dangerous disease. F1/LcrV-based vaccines failed to provide adequate protection in African green monkey model in spite of providing protection in mice and cynomolgus macaques. There is still no explanation for this inconsistent efficacy, and scientists leg behind to search reliable correlate assays for immune protection. These paucities are the main barriers to improve the effectiveness of plague vaccine. In the present scenario, one has to pay special attention to elicit strong cellular immune response in developing a next-generation vaccine against plague. Here, we review the scientific contributions and existing progress in developing subunit vaccines, the role of molecular adjuvants; DNA vaccines; live delivery platforms; and attenuated vaccines developed to counteract virulent strains of Y. pestis.

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“…114,116 MAb 7.3 binds a conformational epitope encrypted by residues 135-275, 117 whereas MAb BA5 recognizes a short linear epitope at residues 196-225. 114 Removal of residues 196-226 from LcrV abolishes the binding of MAb BA5; however, the variant LcrV can still induce plague protective immune responses in mice.…”

Section: Acknowledgementsmentioning

confidence: 99%

Plague vaccines and the molecular basis of immunity againstYersinia pestis

Quenee

Schneewind²

2009

Human Vaccines

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Yersinia pestis is the causative agent of bubonic and pneumonic plague, human diseases with high mortality. Due to the microbe's ability to spread rapidly, plague epidemics present a serious public health threat. A search for prophylactic measures was initially based on historical reports of bubonic plague survivors and their apparent immunity. Due to safety and efficacy concerns, killed whole-cell preparations or live-attenuated plague vaccines are no longer considered in the United States. Vaccine developers have focused on specific subunits of plague bacteria. LcrV, a protein at the tip of type III secretion needles, and F1, the capsular pilus antigen, are both recognized as plague protective antigens. Antibodies against LcrV and F1 interfere with Y. pestis type III injection of host cells. While LcrV is absolutely essential for Y. pestis virulence, expression of F1 is dispensable for plague pathogenesis in small animals, non-human primates and presumably also in humans. Several subunit vaccines, for example rF1+rV (rYP002), rF1V or rV10, are being developed to generate plague protection in humans. Efficacy testing and licensure for human use requires the establishment of correlates for plague immunity.

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Small protective fragments of the Yersinia pestis V antigen

Cited by 24 publications

References 26 publications

Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague

Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague

Plague Vaccine Development: Current Research and Future Trends

Plague vaccines and the molecular basis of immunity againstYersinia pestis

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