Immunogenicity and Protective Immunity against Bubonic Plague and Pneumonic Plague by Immunization of Mice with the Recombinant V10 Antigen, a Variant of LcrV

Department of Microbiology, University of Chicago, 920 E. 58th Street, Chicago, Illinois 60637, USA.
Infection and Immunity (Impact Factor: 3.73). 09/2006; 74(8):4910-4. DOI: 10.1128/IAI.01860-05
Source: PubMed


In contrast to Yersinia pestis LcrV, the recombinant V10 (rV10) variant (lacking residues 271 to 300) does not suppress the release of proinflammatory cytokines
by immune cells. Immunization with rV10 generates robust antibody responses that protect mice against bubonic plague and pneumonic
plague, suggesting that rV10 may serve as an improved plague vaccine.

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Available from: R. William Depaolo,
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    • "The current candidate plague vaccine consists of a F1 capsule protein and the low calcium response (Lcr) V protein or V-antigen either as a mixture of the two proteins or a recombinant fusion of the two proteins [2] [3]. A strong humoral immune response to the individual subunits F1 or V or combined subunits (F1-V or F1+V), or an altered V-antigen (V10) was initially believed to be sufficient to provide protection against a lethal Y. pestis challenge in both mouse and nonhuman primate models of plague [2] [3] [4] [5] [6] [7] [8]. Both murine and human monoclonal antibodies against the subunit components of the plague vaccine have been shown to mediate protection against a lethal plague challenge in mice [9] [10] [11] [12]. "
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    ABSTRACT: The current candidate vaccine against Yersinia pestis infection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host's innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr) 2, 4, and 2/4-double deficient, as well as signal adaptor protein Myd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinated Tlr4 mutant (lipopolysaccharide tolerant) and Myd88-deficient mice were challenged by aerosol with Y. pestis CO92, all but one Tlr4 mutant mice survived the challenge, but no vaccinated Myd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed that Y. pestis was not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge of Y. pestis CO92 in F1-V vaccinated mice.
    Research Journal of Immunology 06/2014; 2014:341820. DOI:10.1155/2014/341820
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    • "However, generally, the protection was due to a mixed Th1/Th2 immune response; (iv) protection provided by anti-LcrV antibodies relied mostly on blocking the type 3 secretion system (T3SS). In this respect, it was possible to disarm unwanted immunomodulating activity of LcrV;29,30,31 and (v) both F1+LcrV and F1−V vaccine candidates are in phase II of clinical trials. "
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    ABSTRACT: Despite many decades of intensive studies of Yersinia pestis, the causative agent of plague, there is no safe and efficient vaccine against this devastating disease. A recently developed F1/V subunit vaccine candidate, which relies mainly on humoral immunity, showed promising results in animal studies; however, its efficacy in humans still has to be carefully evaluated. In addition, those developing next-generation plague vaccines need to pay particular attention to the importance of eliciting cell-mediated immunity. In this review, we analyzed the current progress in developing subunit, DNA and live carrier platforms of delivery by bacterial and viral vectors, as well as approaches for controlled attenuation of virulent strains of Y. pestis.
    Emerging Microbes and Infections 11/2012; 1(11). DOI:10.1038/emi.2012.34 · 2.26 Impact Factor
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    • "Active immunization with rV10 alone or a combination with rF1 protects cynomolgus macaques from pneumonic plague, and the antibodies from macaques provide protection against bubonic plaque in mice (Cornelius et al., 2008). Active immunization with rV10 was also protective in rats and mice (DeBord et al., 2006; Anderson et al., 2009). The rV10 vaccine is undergoing the preclinical efficacy study (Cornelius et al., 2008) along with the FDA pre-investigational new drug authorization review (Quenee and Schneewind, 2009). "
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    ABSTRACT: Pseudomonas aeruginosa possesses a type III secretion system (T3SS) to intoxicate host cells and evade innate immunity. This virulence-related machinery consists of a molecular syringe and needle assembled on the bacterial surface, which allows delivery of T3 effector proteins into infected cells. To accomplish a one-step effector translocation, a tip protein is required at the top end of the T3 needle structure. Strains lacking expression of the functional tip protein fail to intoxicate host cells. P. aeruginosa encodes a T3S that is highly homologous to the proteins encoded by Yersinia spp. The needle-tip proteins of Yersinia, LcrV, and P. aeruginosa, PcrV, share 37% identity and 65% similarity. Other known tip proteins are AcrV (Aeromonas), IpaD (Shigella), SipD (Salmonella), BipD (Burkholderia), EspA (EPEC, EHEC), Bsp22 (Bordetella), with additional proteins identified from various Gram-negative species, such as Vibrio and Bordetella. The tip proteins can serve as a protective antigen or may be critical for sensing host cells and evading innate immune responses. Recognition of the host microenvironment transcriptionally activates synthesis of T3SS components. The machinery appears to be mechanically controlled by the assemblage of specific junctions within the apparatus. These junctions include the tip and base of the T3 apparatus, the needle proteins and components within the bacterial cytoplasm. The tip proteins likely have chaperone functions for translocon proteins, allowing the proper assembly of translocation channels in the host membrane and completing vectorial delivery of effector proteins into the host cytoplasm. Multi-functional features of the needle-tip proteins appear to be intricately controlled. In this review, we highlight the functional aspects and complex controls of T3 needle-tip proteins with particular emphasis on PcrV and LcrV.
    Frontiers in Microbiology 07/2011; 2:142. DOI:10.3389/fmicb.2011.00142 · 3.99 Impact Factor
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