A Novel Multi-Antigen Virally Vectored Vaccine against Mycobacterium avium Subspecies paratuberculosis
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Mendeley | Further Information

{"title"=>"A novel multi-antigen virally vectored vaccine against Mycobacterium avium subspecies paratuberculosis", "type"=>"journal", "authors"=>[{"first_name"=>"Tim J.", "last_name"=>"Bull", "scopus_author_id"=>"7005184531"}, {"first_name"=>"Sarah C.", "last_name"=>"Gilbert", "scopus_author_id"=>"7202266275"}, {"first_name"=>"Saranya", "last_name"=>"Sridhar", "scopus_author_id"=>"24068006900"}, {"first_name"=>"Richard", "last_name"=>"Linedale", "scopus_author_id"=>"6507630301"}, {"first_name"=>"Nicola", "last_name"=>"Dierkes", "scopus_author_id"=>"24175889700"}, {"first_name"=>"Karim", "last_name"=>"Sidi-Boumedine", "scopus_author_id"=>"6507761333"}, {"first_name"=>"John", "last_name"=>"Hermon-Taylor", "scopus_author_id"=>"7005269548"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"43349095488", "pui"=>"351659529", "pmid"=>"18043737", "issn"=>"19326203", "scopus"=>"2-s2.0-43349095488", "doi"=>"10.1371/journal.pone.0001229"}, "id"=>"7c4acc0a-8f89-3551-9e2c-885407e3e389", "abstract"=>"BACKGROUND: Mycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal inflammation in many species including primates. Humans are exposed through milk and from sources of environmental contamination. Hitherto, the only vaccines available against Mycobacterium avium subspecies paratuberculosis have been limited to veterinary use and comprised attenuated or killed organisms.\\n\\nMETHODS: We developed a vaccine comprising a fusion construct designated HAV, containing components of two secreted and two cell surface Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery vectors. Full length expression of the predicted 95 kDa fusion protein was confirmed.\\n\\nPRINCIPAL FINDINGS: Vaccination of naïve and Mycobacterium avium subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or Ad5-prime/MVA-boost protocols was highly immunogenic resulting in significant IFN-gamma ELISPOT responses by splenocytes against recombinant vaccine antigens and a range of HAV specific peptides. This included strong recognition of a T-cell epitope GFAEINPIA located near the C-terminus of the fusion protein. Antibody responses to recombinant vaccine antigens and HAV specific peptides but not GFAEINPIA, also occurred. No immune recognition of vaccine antigens occurred in any sham vaccinated Mycobacterium avium subspecies paratuberculosis infected mice. Vaccination using either protocol significantly attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection measured by qPCR in spleen and liver and the Ad5-prime/MVA-boost protocol also conferred some protection against subsequent challenge. No adverse effects of vaccination occurred in any of the mice.\\n\\nCONCLUSIONS/SIGNIFICANCE: A range of modern veterinary and clinical vaccines for the treatment and prevention of disease caused by Mycobacterium avium subspecies paratuberculosis are needed. The present vaccine proved to be highly immunogenic without adverse effect in mice and both attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection and conferred protection against subsequent challenge. Further studies of the present vaccine in naturally infected animals and humans are indicated.", "link"=>"http://www.mendeley.com/research/novel-multiantigen-virally-vectored-vaccine-against-mycobacterium-avium-subspecies-paratuberculosis", "reader_count"=>30, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>5, "Veterinary Science and Veterinary Medicine"=>4, "Social Sciences"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>4}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>4}}, "reader_count_by_country"=>{"Japan"=>2, "Egypt"=>1, "United Kingdom"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/942389"], "description"=>"<p>Strategy used for the insertion of HAV into pSG2 plasmid, Ad5 and MVA vectors.</p>", "links"=>[], "tags"=>["insertion", "hav", "psg2", "ad5", "mva"], "article_id"=>612787, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.g008", "stats"=>{"downloads"=>2, "page_views"=>47, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Strategy_used_for_the_insertion_of_HAV_into_pSG2_plasmid_Ad5_and_MVA_vectors_/612787", "title"=>"Strategy used for the insertion of HAV into pSG2 plasmid, Ad5 and MVA vectors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:33:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/942143"], "description"=>"<p>A) ELISA IgG<sub>total</sub> responses in naïve uninfected mice, to peptide pools (A–N), the peptide epitope F9.1 (sequence GFAEINPIA) and recombinant vaccine antigens (AhpC, Mpa) 4 weeks after Ad5.HAV-prime/MVA.HAV-boost vaccination. C = Control (Grp3), V = Vaccine (Grp4) from Experiment 1B. B) ELISA IgG<sub>total</sub> responses to peptide pool A, the peptide epitope F9.1 (sequence GFAEINPIA) and rec.AhpC following prophylactic or therapeutic vaccination in low dose (10<sup>5</sup>) and high dose (10<sup>8</sup>) MAP K37 infection. C = Vector only control, V = Vaccine. Low dose prophylactic results correspond to Control (Grp12) and Vaccine (Grp13); Low dose therapeutic results correspond to Control (Grp17) and Vaccine (Grp18); High dose prophylactic results correspond to Control (Grp14) and Vaccine (Grp15); High dose therapeutic results correspond to Control (Grp19) and Vaccine (Grp20) as shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001229#pone-0001229-g002\" target=\"_blank\">Fig. 2</a>.</p>", "links"=>[], "tags"=>["responses"], "article_id"=>612553, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.g006", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antibody_responses_to_vaccination_/612553", "title"=>"Antibody responses to vaccination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:32:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/942515"], "description"=>"<p>nd = not done ; NS = not significant</p>*<p>Comparison of vaccine and vector only</p>", "links"=>[], "tags"=>["reductions", "loads", "spleen"], "article_id"=>612913, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.t001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_mean_fold_reductions_in_MAP_loads_in_spleen_and_liver_in_response_to_vaccination_/612913", "title"=>"Summary of mean fold reductions in MAP loads in spleen and liver in response to vaccination", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 11:34:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/941888"], "description"=>"<p>This was performed by qPCR in A) spleen and B) liver 28 weeks after prophylactic or therapeutic pSG2-prime/MVA-boost vaccination protocols in mice challenged i.p. with 10<sup>7</sup> MAP K10(m). Significant responses are indicated.</p>", "links"=>[], "tags"=>["immunology", "Infectious diseases", "microbiology"], "article_id"=>612297, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.g004", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitation_of_the_tissue_load_of_MAP_/612297", "title"=>"Quantitation of the tissue load of MAP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:31:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/941537"], "description"=>"<p>Coding and amino acid sequences of the four MAP antigen fusion protein HAV comprising AhpC MAP1589c (Yellow), Gsd MAP1234 (Blue), p12 MAP2444c (Pink), Mpa MAP1235 (Magenta), Ubiquitin leader (Green), pK C-terminal tag (Red). The strong murine T-cell epitope found in Mpa designated peptide F9.1 is boxed.</p>", "links"=>[], "tags"=>["fusion", "designated"], "article_id"=>611951, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.g001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structure_and_composition_of_the_MAP_vaccine_fusion_construct_designated_HAV_/611951", "title"=>"Structure and composition of the MAP vaccine fusion construct designated HAV.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:28:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/941646"], "description"=>"<p>Viral doses were 10<sup>8</sup> pfu per mouse. Routes of administration were i.m. for pSG2, i.v. for MVA boost in Experiments 1A and 2, and i.d.p. (intradermal into pinna) for Ad5 and MVA vaccination in Experiment 1B and Experiment 3.</p>", "links"=>[], "tags"=>["vaccination"], "article_id"=>612061, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.g002", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protocols_for_vaccination_studies_/612061", "title"=>"Protocols for vaccination studies.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:29:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/942286"], "description"=>"<p>qPCR in A) spleen and B) liver 12 weeks after prophylactic or therapeutic Ad5-prime/MVA-boost vaccination protocols in mice challenged with either low dose (10<sup>5</sup>) or high dose (10<sup>8</sup>) MAP K37 (Experiment 3). Significant responses to vaccination are indicated.</p>", "links"=>[], "tags"=>["immunology", "Infectious diseases", "microbiology"], "article_id"=>612687, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.g007", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitation_of_the_tissue_load_of_MAP_/612687", "title"=>"Quantitation of the tissue load of MAP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:33:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/941766"], "description"=>"<p>These include responses to peptide pools, selected peptide (F9.1), and recombinant vaccine antigens (AhpC, Mpa) in Control (Grp 1) mice (C) and Vaccine (Grp 2) mice (V), 4 weeks after immunisation A) using pSG2-prime/MVA-boost (Experiment 1A) or B) Ad5-prime/MVA-boost (Experiment 1B). Significant responses are indicated.</p>", "links"=>[], "tags"=>["splenocyte"], "article_id"=>612178, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ELISPOT_splenocyte_responses_/612178", "title"=>"ELISPOT splenocyte responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:30:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/942069"], "description"=>"<p>These include responses to peptide pools (A, J and L), the peptide epitope F9.1 (sequence GFAEINPIA) and rec.AhpC following prophylactic or therapeutic vaccination in A) low dose (10<sup>5</sup>) and B) high dose (10<sup>8</sup>) MAP K37 infection. C = Vector only control, V = Vaccine. Low dose prophylactic results correspond to Control (Grp12) and Vaccine (Grp13); Low dose therapeutic results correspond to Control (Grp17) and Vaccine (Grp18); High dose prophylactic results correspond to Control (Grp14) and Vaccine (Grp15); High dose therapeutic results correspond to Control (Grp19) and Vaccine (Grp20) as shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001229#pone-0001229-g002\" target=\"_blank\">Fig. 2</a>.</p>", "links"=>[], "tags"=>["splenocyte"], "article_id"=>612479, "categories"=>["Microbiology", "Infectious Diseases", "Immunology"], "users"=>["Tim J. Bull", "Sarah C. Gilbert", "Saranya Sridhar", "Richard Linedale", "Nicola Dierkes", "Karim Sidi-Boumedine", "John Hermon-Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001229.g005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ELISPOT_splenocyte_responses_/612479", "title"=>"ELISPOT splenocyte responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:32:05"}

PMC Usage Stats | Further Information

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Relative Metric

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