rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector
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{"title"=>"rBCG induces strong antigen-specific T cell responses in Rhesus Macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector", "type"=>"journal", "authors"=>[{"first_name"=>"Isabelle", "last_name"=>"Magalhaes", "scopus_author_id"=>"20433844400"}, {"first_name"=>"Donata R.", "last_name"=>"Sizemore", "scopus_author_id"=>"35552719100"}, {"first_name"=>"Raija K.", "last_name"=>"Ahmed", "scopus_author_id"=>"35474044900"}, {"first_name"=>"Stefanie", "last_name"=>"Mueller", "scopus_author_id"=>"57197917406"}, {"first_name"=>"Lena", "last_name"=>"Wehlin", "scopus_author_id"=>"56094549000"}, {"first_name"=>"Charles", "last_name"=>"Scanga", "scopus_author_id"=>"6701713751"}, {"first_name"=>"Frank", "last_name"=>"Weichold", "scopus_author_id"=>"6603757354"}, {"first_name"=>"Giulia", "last_name"=>"Schirru", "scopus_author_id"=>"8607922000"}, {"first_name"=>"Maria Grazia", "last_name"=>"Pau", "scopus_author_id"=>"7005060271"}, {"first_name"=>"Jaap", "last_name"=>"Goudsmit", "scopus_author_id"=>"35374719700"}, {"first_name"=>"Sharon", "last_name"=>"Kühlmann-Berenzon", "scopus_author_id"=>"16444926800"}, {"first_name"=>"Mats", "last_name"=>"Spångberg", "scopus_author_id"=>"26650238000"}, {"first_name"=>"Jan", "last_name"=>"Andersson", "scopus_author_id"=>"7201501336"}, {"first_name"=>"Hans", "last_name"=>"Gaines", "scopus_author_id"=>"55159980000"}, {"first_name"=>"Rigmor", "last_name"=>"Thorstensson", "scopus_author_id"=>"7003874441"}, {"first_name"=>"Yasir A.W.", "last_name"=>"Skeiky", "scopus_author_id"=>"7003995577"}, {"first_name"=>"Jerry", "last_name"=>"Sadoff", "scopus_author_id"=>"35466357200"}, {"first_name"=>"Markus", "last_name"=>"Maeurer", "scopus_author_id"=>"7004422039"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "sgr"=>"56849108004", "isbn"=>"1932-6203; 1932-6203", "doi"=>"10.1371/journal.pone.0003790", "pui"=>"352749093", "pmid"=>"19023426", "scopus"=>"2-s2.0-56849108004"}, "id"=>"3c077e65-167f-37e8-b8b4-074647cb0333", "abstract"=>"BACKGROUND: BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing perfringolysin (in 6 animals) followed by two boosts (delivered intramuscullary) with non-replicating adenovirus 35 (rAd35) expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques (Macaca mulatta). Control animals received diluent (3 animals).\\n\\nMETHODS AND FINDINGS: Cellular immune responses were analyzed longitudinally (12 blood draws for each animal) using intracellular cytokine staining (TNF-alpha, IL-2 and IFN-gamma), T cell proliferation was measured in CD4(+), CD8alpha/beta(+), and CD8alpha/alpha(+) T cell subsets and IFN-gamma production was tested in 7 day PBMC cultures (whole blood cell assay, WBA) using Ag85A, Ag85B, TB10.4 recombinant proteins, PPD or BCG as stimuli. Animals primed with AFRO-1 showed i) increased Ag85B-specific IFN-gamma production in the WBA assay (median >400 pg/ml for 6 animals) one week after the first boost with adenoviral-delivered TB-antigens as compared to animals primed with BCG (<200 pg/ml), ii) stronger T cell proliferation in the CD8alpha/alpha(+) T cell subset (proliferative index 17%) as compared to BCG-primed animals (proliferative index 5% in CD8alpha/alpha(+) T cells). Polyfunctional T cells, defined by IFN-gamma, TNF-alpha and IL-2 production were detected in 2/6 animals primed with AFRO-1 directed against Ag85A/b and TB10.4; 4/6 animals primed with BCG showed a Ag85A/b responses, yet only a single animal exhibited Ag85A/b and TB10.4 reactivity.\\n\\nCONCLUSION: AFRO-1 induces qualitatively and quantitatively different cellular immune responses as compared with BCG in rhesus macaques. Increased IFN-gamma-responses and antigen-specific T cell proliferation in the CD8alpha/alpha+ T cell subset represents a valuable marker for vaccine-take in BCG-based TB vaccine trials.", "link"=>"http://www.mendeley.com/research/rbcg-induces-strong-antigenspecific-t-cell-responses-rhesus-macaques-primeboost-setting-adenovirus-3", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>3, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>4, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/915547"], "description"=>"<p>The median of IFN-γ production (measured by ELISA) in whole blood cultures for each group in response to different <i>Mtb</i> antigen stimulation was assessed. Stronger IFN-γ production was seen in animals primed with AFRO-1 in response to Ag85A and Ag85B, as compared to animals primed with BCG one week after the first boost with AERAS-402.</p>", "links"=>[], "tags"=>["bcg", "afro-1", "induces", "antigen"], "article_id"=>585981, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Isabelle Magalhaes", "Donata R. Sizemore", "Raija K. Ahmed", "Stefanie Mueller", "Lena Wehlin", "Charles Scanga", "Frank Weichold", "Giulia Schirru", "Maria Grazia Pau", "Jaap Goudsmit", "Sharon Kuhlmann-Berenzon", "Mats Spångberg", "Jan Andersson", "Hans Gaines", "Rigmor Thorstensson", "Yasir A. W. Skeiky", "Jerry Sadoff", "Markus Maeurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003790.g002", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Prime_with_BCG_or_AFRO_1_induces_a_different_IFN_production_profile_in_response_to_Mtb_antigen_stimulation_/585981", "title"=>"Prime with BCG or AFRO-1 induces a different IFN-γ production profile in response to <i>Mtb</i> antigen stimulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 07:33:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/915426"], "description"=>"<p>NHPs were boosted with AERAS-402 fifteen and twenty-seven weeks after the prime with BCG or AFRO-1, Animals in group 1 were primed with BCG, animals in group 2 with the recombinant BCG (AFRO-1) which combines endosomal escape, TB10.4 expression and over-expression of Ag85A and Ag85B. Animals in both groups were boosted with the non-replicating adenovirus 35 AERAS-402 which expresses the Ag85A, Ag85B and TB10.4 fusion protein. Animals in group 3 received the diluent (control group).</p>", "links"=>[], "tags"=>["timeline", "sampling"], "article_id"=>585862, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Isabelle Magalhaes", "Donata R. Sizemore", "Raija K. Ahmed", "Stefanie Mueller", "Lena Wehlin", "Charles Scanga", "Frank Weichold", "Giulia Schirru", "Maria Grazia Pau", "Jaap Goudsmit", "Sharon Kuhlmann-Berenzon", "Mats Spångberg", "Jan Andersson", "Hans Gaines", "Rigmor Thorstensson", "Yasir A. W. Skeiky", "Jerry Sadoff", "Markus Maeurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003790.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Study_Timeline_and_Sampling_Schedule_/585862", "title"=>"Study Timeline and Sampling Schedule.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 07:33:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/915694"], "description"=>"<p>The median of the proliferation index (% of blasts in response to antigen stimulation - % of blasts in negative control) in response to <i>Mtb</i> antigens was determined by flow cytometric analysis. Differential expansion of T cell subsets was gauged by gating on T cell subsets, i.e. CD4<sup>+</sup>, CD8alpha/beta<sup>+</sup> and CD8alpha/alpha<sup>+</sup>. Animals primed with AFRO-1 showed stronger proliferation in response to Ag85B stimulation within CD4<sup>+</sup> T cells (A) and CD8alpha/alpha<sup>+</sup> T cells (B) as compared to animals primed with BCG one week after the first boost with AERAS-402. No difference was detectable between animals primed with AFRO-1 or BCG in the CD8alpha/beta<sup>+</sup> T cell compartment (C).</p>", "links"=>[], "tags"=>["afro-1", "induces", "proliferation", "ag85b-specific", "cells"], "article_id"=>586132, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Isabelle Magalhaes", "Donata R. Sizemore", "Raija K. Ahmed", "Stefanie Mueller", "Lena Wehlin", "Charles Scanga", "Frank Weichold", "Giulia Schirru", "Maria Grazia Pau", "Jaap Goudsmit", "Sharon Kuhlmann-Berenzon", "Mats Spångberg", "Jan Andersson", "Hans Gaines", "Rigmor Thorstensson", "Yasir A. W. Skeiky", "Jerry Sadoff", "Markus Maeurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003790.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Prime_with_AFRO_1_induces_proliferation_of_Ag85B_specific_T_cells_in_CD4_and_CD8alpha_alpha_T_cells_/586132", "title"=>"Prime with AFRO-1 induces proliferation of Ag85B-specific T cells in CD4<sup>+</sup> and CD8alpha/alpha<sup>+</sup> T cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 07:34:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/915828"], "description"=>"<p>Production of IL-2, IFN-gamma, and TNF-alpha within CD4<sup>+</sup> (A), CD8alpha/alpha<sup>+</sup> (B) or CD8alpha/beta<sup>+</sup> T cells (C) in response to Ag85A/b or TB10.4 peptide pool stimulation was assessed by flow cytometry. The average of duplicates of the total frequency of IL-2, IFN-gamma, or TNF-alpha producing T cells stimulated with Ag85A/b or TB10.4 peptide pools were plotted. The proportion of total T cells expressing any of the seven possible combinations of IL-2, IFN-gamma, and TNF-alpha from selected animals, either in response to antigen, maximal stimulation (PMA/ionomycin) and medium (control) are shown in pie charts. Ag85A/B and TB10.4-specific T cells were observed in 2/6 animals primed with AFRO-1, and in 4/6 animals primed with BCG one week after the first boost with AERAS-402.</p>", "links"=>[], "tags"=>["cells", "animals", "primed", "afro-1"], "article_id"=>586266, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Isabelle Magalhaes", "Donata R. Sizemore", "Raija K. Ahmed", "Stefanie Mueller", "Lena Wehlin", "Charles Scanga", "Frank Weichold", "Giulia Schirru", "Maria Grazia Pau", "Jaap Goudsmit", "Sharon Kuhlmann-Berenzon", "Mats Spångberg", "Jan Andersson", "Hans Gaines", "Rigmor Thorstensson", "Yasir A. W. Skeiky", "Jerry Sadoff", "Markus Maeurer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0003790.g004", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Polyfunctional_Ag85A_b_and_TB10_4_specific_T_cells_are_present_in_animals_primed_with_AFRO_1_or_BCG_/586266", "title"=>"Polyfunctional Ag85A/b and TB10.4-specific T cells are present in animals primed with AFRO-1 or BCG.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 07:35:31"}

PMC Usage Stats | Further Information

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Relative Metric

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