A parenteral DNA vaccine protects against pneumonic plague

Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
Vaccine (Impact Factor: 3.62). 02/2010; 28(18):3219-30. DOI: 10.1016/j.vaccine.2010.02.022
Source: PubMed


The chemokine, lymphotactin (LTN), was tested as a molecular adjuvant using bicistronic DNA vaccines encoding the protective Yersinia capsular (F1) antigen and virulence antigen (V-Ag) as a F1-V fusion protein. The LTN-encoding F1-V or V-Ag vaccines were given by the intranasal (i.n.) or intramuscular (i.m.) routes, and although serum IgG and mucosal IgA antibodies (Abs) were induced, F1-Ag boosts were required for robust anti-F1-Ag Abs. Optimal efficacy against pneumonic plague was obtained in mice i.m.-, not i.n.-immunized with these DNA vaccines. These vaccines stimulated elevated Ag-specific Ab-forming cells and mixed Th cell responses, with Th17 cells markedly enhanced by i.m. immunization. These results show that LTN can be used as a molecular adjuvant to enhance protective immunity against plague.

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Available from: Kathryn Holderness, Jun 12, 2014
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    • "This approach suggested a number of ways to develop protective DNA vaccines (Wang et al., 2010). Immunization with the F1-V based DNA vaccine and the adjuvant, lymphotactin (LTN) resulted in high levels of serum IgG and mucosal IgA antibodies (Yamanaka et al., 2010). The LcrV based DNA vaccine elicited a CD8+ immune response against specific epitopes of this antigen (Wang et al., 2011). "

    Bioterrorism, 01/2012; , ISBN: 978-953-51-0205-2
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    • "Unlike the KWCVs, the rF1-/V-antigen combination has been demonstrated to protect both mice and macaques against pneumonic plague [24–27], representing a significant advance in candidate countermeasures for plague infection. Different presentations of F1/V have been studied including DNA vaccines [28], oral formulations [29], and live vaccine-vectored expression from, for example, salmonella strains [30]. "
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    01/2012; 2012(2090-3480):365980. DOI:10.1155/2012/365980
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    • "However, poorer protection was observed when IL-12 was over-expressed, strongly suggesting that the expression levels of various molecular adjuvants, like IL-12, need to be optimized prior to their inclusion in DNA-based vaccines (Yamanaka et al. 2008). When another putative molecular adjuvant, the chemokine lymphotactin, was tested after being expressed and produced in a DNA vaccine co-expressing/producing the F1-V fusion protein, its intramuscular administration conferred better protection against a subsequent pneumonic plague challenge than did an IN administration of the same vaccine (Yamanaka et al. 2010). Although promising, it becomes imperative that putative molecular adjuvants be evaluated by co-expressing multiple plague antigenencoding genes from DNA vaccines and be administered via multiple routes in animals before definitive statements are made about their potential usefulness in DNA-based plague vaccines. "
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