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). "

    Full-text · Chapter · Jan 2012
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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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    ABSTRACT: One of the difficulties in developing countermeasures to biothreat agents is the challenge inherent in demonstrating their efficacy in man. Since the first publication of the Animal Rule by the FDA, there has been increased discussion of potential correlates of protection in animal models and their use to establish surrogate markers of efficacy in man. The latter need to be relatively easy to measure in assays that are at least qualified, if not validated, in order to derive a quantitative assessment of the clinical benefit conferred. The demonstration of safety and clinical benefit is essential to achieve regulatory approval for countermeasures for which clinical efficacy cannot be tested directly, as is the case for example, for biodefence vaccines. Plague is an ancient, serious infectious disease which is still endemic in regions of the modern world and is a potential biothreat agent. This paper discusses potential immune correlates of protection for plague, from which it may be possible to derive surrogate markers of efficacy, in order to predict the clinical efficacy of candidate prophylaxes and therapies.
    Full-text · Article · Jan 2012
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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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