Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine

DSTL, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Vaccine (Impact Factor: 3.49). 06/2006; 24(20):4433-9. DOI: 10.1016/j.vaccine.2005.12.016
Source: PubMed

ABSTRACT Protection against virulent plague challenge by the parenteral and aerosol routes was afforded by a single administration of microencapsulated Caf1 and LcrV antigens from Yersinia pestis in BALB/c mice. Recombinant Caf1 and LcrV were individually encapsulated in polymeric microspheres, to the surface of which additional antigen was adsorbed. The microspheres containing either Caf1 or LcrV were blended and used to immunise mice on a single occasion, by either the intra-nasal or intra-muscular route. Both routes of immunisation induced systemic and local immune responses, with high levels of serum IgG being developed in response to both vaccine antigens. In Elispot assays, secretion of cytokines by spleen and draining lymph node cells was demonstrated, revealing activation of both Th1 and Th2 associated cytokines; and spleen cells from animals immunised by either route were found to proliferate in vitro in response to both vaccine antigens. Virulent challenge experiments demonstrated that non-invasive immunisation by intra-nasal instillation can provide strong systemic and local immune responses and protect against high level challenge. Microencapsulation of these vaccine antigens has the added advantage that controlled release of the antigens occurs in vivo, so that protective immunity can be induced after only a single immunising dose.

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    • "Multiple biodegradable polymers, including polyesters, have been studied as vaccine delivery vehicles [4], [13]. By comparison, the controlled release and adjuvanticity provided by novel polyanhydride carriers, first pioneered by Robert Langer of MIT in the 1980s [14], [15], allows for immune system activation, reduction of antigenic dose, prolonged antigen exposure, stability of the encapsulated protein antigen, and immune modulation [16]–[25]. "
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    ABSTRACT: Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant protein F1-V alone and MPLA-adjuvanted F1-V, the nanoparticle-based vaccination regimen induced an immune response that was characterized by high titer and high avidity IgG1 anti-F1-V antibody that persisted for at least 23 weeks post-vaccination. After challenge, no Y. pestis were recovered from the lungs, livers, or spleens of mice vaccinated with the nanoparticle-based formulation and histopathological appearance of lung, liver, and splenic tissues from these mice post-vaccination was remarkably similar to uninfected control mice.
    PLoS ONE 03/2011; 6(3):e17642. DOI:10.1371/journal.pone.0017642 · 3.23 Impact Factor
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    • "Treponema pallidum TmpB Yes P19649 [47] Treponema pallidum Antigen TpF1 Yes P16665 [14] Yersinia pestis V antigen Yes P21206 [48] Yersinia pestis Caf1 Yes P26948 [49] Bordetella pertussis Acetyl-coenzyme A carboxylase carboxyl transferase subunit alpha No Q7VX94 Bordetella pertussis Holo-[acyl-carrier-protein] synthase No Q7VWV9 Borrelia burgdorferi Outer surface protein D (ospD) No Q05051 Borrelia burgdorferi 6-phosphogluconolactonase No O51240 Borrelia burgdorferi Acetate kinase No O51567 Borrelia burgdorferi Holo-[acyl-carrier-protein] synthase No O51043 A u t h o r ' s p e r s o n a l c o p y 862 I.A. Doytchinova, D.R. Flower / Vaccine 25 (2007) 856–866 Appendix A (Continued ) Species Training set Protein Protection Swiss-prot Reference Borrelia burgdorferi Adenine deaminase No O50821 Brucella abortus Regulatory protein BvrR No O67996 Brucella abortus Dihydrolipoamide succinyl transferase No O85598 Brucella melitensis Translation initiation factor IF-2 No Q8YEB3 Campylobacter coli Dihydrodipicolinate reductase No Q5HWX1 Chlamydia trachomatis Chorismate synthase No O84373 Clostridium perfringens Shikimate dehydrogenase No Q8XMI8 Clostridium perfringens Chloramphenicol acetyltransferase No P26826 Clostridium tetani Transporter No Q890Y8 Coccidioides immitis Isocitrate lyase No Q96TP5 Coccidioides immitis Glyceraldehyde-3-phosphate dehydrogenase No Q8J1H3 Coccidioides posadasii Orotidine 5 -phosphate decarboxylase No Q4VWW3 Corynebacterium pseudotuberculosis 3-dehydroquinate synthase No P96749 Echinococcus granulosus Paramyosin No P35417 Escherichia coli Pantoate–beta-alanine ligase No Q8X930 Escherichia coli UPF0053 inner membrane protein yoaE No P0AEC1 Haemophilus influenzae Biotin carboxylase No P43873 Haemophilus influenzae Nucleoside diphosphate kinase No P43802 Haemophilus influenzae UvrABC system protein A No Q4QNT9 Helicobacter pylori Chemotaxis protein cheY homolog No Q9ZM64 Helicobacter pylori Protein-export membrane protein secF No Q9ZJ65 Helicobacter pylori Carbonic anhydrase No O25798 Helicobacter pylori Methylase No Q3S3S0 Helicobacter pylori Inorganic pyrophosphatase No Q8GK72 Legionella pneumophila Histidinol dehydrogenase No Q5X5W9 Legionella pneumophila Aconitate hydratase No Q5X4L7 Legionella pneumophila Triosephosphate isomerase No Q5ZRT6 Listeria monocytogenes Chemotaxis protein cheY No P0A4H5 Listeria monocytogenes Manganese transport system membrane protein mntC No Q8Y652 Mycobacterium avium Alanine and proline-rich secreted protein apa No Q48919 Mycobacterium avium Transposase No Q48909 Mycobacterium bovis Ribonuclease HII No Q7TXM7 Mycobacterium bovis Histidyl-tRNA synthetase No P67484 Mycobacterium tuberculosis PstS-1 No P15712 Mycobacterium tuberculosis PE35 No Q79F93 Mycobacterium tuberculosis Rv3878 No O69742 Mycobacterium tuberculosis Rv3879c No O69743 Mycobacterium tuberculosis Tryptophan synthase beta chain No P66984 Mycobacterium tuberculosis Thioredoxin reductase No P52214 Mycobacterium tuberculosis Transcription elongation factor greA No P64279 Mycobacterium tuberculosis 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase No P0A5R6 Mycobacterium tuberculosis DNA gyrase subunit A No Q07702 Mycobacterium tuberculosis DNA gyrase subunit B No Q9L7L3 Mycobacterium tuberculosis Delta-aminolevulinic acid dehydratase No O33357 Neisseria meningitidis Amylosucrase No Q84HD6 Neisseria meningitidis Chorismate synthase No Q9JY99 Neisseria meningitidis Argininosuccinate synthase No Q9JXC1 Pseudomonas aeruginosa Gentamicin 3 -acetyltransferase No P23181 Pseudomonas aeruginosa Biotin carboxylase No P37798 Pseudomonas aeruginosa Isocitrate lyase No Q9I0K4 Pseudomonas aeruginosa Glycosyl transferase alg8 No Q52463 Rickettsia tsutsugamushi Rickettsia tsutsugamushi No Q53247 Shigella dysenteriae RepA No Q326M5 Staphylococcus aureus 6-phosphogluconate dehydrogenase No Q931R3 Staphylococcus aureus Acetate kinase No Q931P6 Staphylococcus aureus Fructose-bisphosphate aldolase No Q6G7I5 Streptococcus agalactiae Arginine deiminase No Q8E2K0 Streptococcus pneumoniae Dihydrodipicolinate synthase No Q97R25 Streptococcus pneumoniae Tyrosine recombinase xerC No Q7ZAK7 Streptococcus pneumoniae Initiation-control protein yabA No Q97R89 A u t h o r ' s p e r s o n a l c o p y I.A. Doytchinova, D.R. Flower / Vaccine 25 (2007) 856–866 863 Appendix A (Continued ) Species Training set Protein Protection Swiss-prot Reference Streptococcus pneumoniae Capsular polysaccharide synthesis protein No O07341 Streptococcus pneumoniae Transposase No O33754 Streptococcus pyogenes Alanine racemase No Q99Y98 Treponema pallidum TmpA No P07643 Treponema pallidum TmpC No P29724 Treponema pallidum Methionine aminopeptidase No O83814 Treponema pallidum Chemotaxis protein cheA No P96123 Yersinia pestis Uronate isomerase No Q8ZIC6 Yersinia pestis Flavoprotein wrbA No Q8ZF61 Species Test set Protein Protection Swiss-prot Reference Escherichia coli FepA Yes P05825 [50] Escherichia coli Cell division inhibitor Yes P0AFZ6 [50] Escherichia coli Colicin I receptor precursor Yes P17315 [50] Klebsiella pneumoniae OmpA Yes P24017 [50] "
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    ABSTRACT: Subunit vaccine discovery is an accepted clinical priority. The empirical approach is time- and labor-consuming and can often end in failure. Rational information-driven approaches can overcome these limitations in a fast and efficient manner. However, informatics solutions require reliable algorithms for antigen identification. All known algorithms use sequence similarity to identify antigens. However, antigenicity may be encoded subtly in a sequence and may not be directly identifiable by sequence alignment. We propose a new alignment-independent method for antigen recognition based on the principal chemical properties of protein amino acid sequences. The method is tested by cross-validation on a training set of bacterial antigens and external validation on a test set of known antigens. The prediction accuracy is 83% for the cross-validation and 80% for the external test set. Our approach is accurate and robust, and provides a potent tool for the in silico discovery of medically relevant subunit vaccines.
    Vaccine 02/2007; 25(5):856-66. DOI:10.1016/j.vaccine.2006.09.032 · 3.49 Impact Factor
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    Annual Review of Microbiology 01/1955; 9:253-76. DOI:10.1146/annurev.mi.09.100155.001345 · 13.02 Impact Factor
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