Vaccination with a novel Yersinia pestis single component, two-valent LcrV-F1 vaccine protects against lethal intranasal challenge.

Yersinia pestis, a category A select agent is the causative agent of pneumonic plague. Currently, an effective vaccine has yet to be developed to protect against pneumonic infection therefore, Y. pestis weaponization and aerosolization is considered a bioterrorism threat. Here, we investigated the efficacy of a novel plague vaccine containing the low-calcium-response V ( LcrV) and the Fraction 1 capsular (F1) proteins, expressed as fusions to the thermostable lechinase enzyme (LicKM) of Clostridium thermocellum and purified from Nicotiana benthamiana plants. BALB/c mice primed and boosted with 1?g of this single component two-valent LcrV-F1 vaccine in alhydrogel provided protection against a lethal intranasal challenge with Y. pestis KIM D27. We determined this protection was antibody mediated as vaccination generated high IgG antibody titers. Additionally, adoptive transfer of serum from vaccinated mice to naïve mice protected against a lethal challenge while treatment of this serum using a Protein G column negated this serum-mediated protection. In order to determine if this vaccination regimen also resulted in memory T cell production, CD4 T cells isolated from vaccinated mice and subjected to in vitro restimulation with either LcrV or F1-LicKM fusion resulted in IL-2 production. Here, we have determined that vaccination using this novel LcrV-F1 LicKM fusion results in humoral immunity and protection against lethal Y. pestis KIM D27 infection.