title: Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague.
abstract: Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague models. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a Tobacco Mosaic Virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, United States. Electronic address: paul_arnaboldi@nymc.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Arnaboldi
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: Mariya
authors.initials: M
authors.lastname: Sambir
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: D'Arco
authors.affiliation: The Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, United States.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Peters
authors.affiliation: Falco Biotherapeutics, Leiden, Netherlands.
authors.forename: Jos F M L
authors.initials: JF
authors.lastname: Seegers
authors.affiliation: The Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, United States.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.affiliation: Department of Biology and Pharmaceutical Sciences, College of Pharmacy, Touro University California, Vallejo, CA 94592, United States.
authors.forename: Alison A
authors.initials: AA
authors.lastname: McCormick
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Dattwyler
mesh_terms: D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D006801:Humans; D048191:Lactiplantibacillus plantarum / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000517:prevention & control*; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014027:Tobacco Mosaic Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D037521:Virulence Factors
keywords: Mucosal vaccination; Pneumonic plague; Tobacco Mosaic Virus; Yersinia pestis