Dual Neonate Vaccine Platform against HIV-1 and M. tuberculosis
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{"title"=>"Dual neonate vaccine platform against HIV-1 and M. tuberculosis", "type"=>"journal", "authors"=>[{"first_name"=>"Richard", "last_name"=>"Hopkins", "scopus_author_id"=>"7202014810"}, {"first_name"=>"Anne", "last_name"=>"Bridgeman", "scopus_author_id"=>"7006340835"}, {"first_name"=>"Joan", "last_name"=>"Joseph", "scopus_author_id"=>"7401935768"}, {"first_name"=>"Sarah C.", "last_name"=>"Gilbert", "scopus_author_id"=>"7202266275"}, {"first_name"=>"Helen", "last_name"=>"McShane", "scopus_author_id"=>"7003769588"}, {"first_name"=>"Tomáš", "last_name"=>"Hanke", "scopus_author_id"=>"35415389000"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"361758757", "sgr"=>"79955939284", "issn"=>"19326203", "pmid"=>"21603645", "scopus"=>"2-s2.0-79955939284", "doi"=>"10.1371/journal.pone.0020067", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"9f24258f-c256-3d7d-b463-19b8f16ab735", "abstract"=>"Acquired immunodeficiency syndrome and tuberculosis (TB) are two of the world's most devastating diseases. The first vaccine the majority of infants born in Africa receive is Mycobacterium bovis bacillus Calmette-Guérin (BCG) as a prevention against TB. BCG protects against disseminated disease in the first 10 years of life, but provides a variable protection against pulmonary TB and enhancing boost delivered by recombinant modified vaccinia virus Ankara (rMVA) expressing antigen 85A (Ag85A) of M. tuberculosis is currently in phase IIb evaluation in African neonates. If the newborn's mother is positive for human immunodeficiency virus type 1 (HIV-1), the baby is at high risk of acquiring HIV-1 through breastfeeding. We suggested that a vaccination consisting of recombinant BCG expressing HIV-1 immunogen administered at birth followed by a boost with rMVA sharing the same immunogen could serve as a strategy for prevention of mother-to-child transmission of HIV-1 and rMVA expressing an African HIV-1-derived immunogen HIVA is currently in phase I trials in African neonates. Here, we aim to develop a dual neonate vaccine platform against HIV-1 and TB consisting of BCG.HIVA administered at birth followed by a boost with MVA.HIVA.85A. Thus, mMVA.HIVA.85A and sMVA.HIVA.85A vaccines were constructed, in which the transgene transcription is driven by either modified H5 or short synthetic promoters, respectively, and tested for immunogenicity alone and in combination with BCG.HIVA(222). mMVA.HIVA.85A was produced markerless and thus suitable for clinical manufacture. While sMVA.HIVA.85A expressed higher levels of the immunogens, it was less immunogenic than mMVA.HIVA.85A in BALB/c mice. A BCG.HIVA(222)-mMVA.HIVA.85A prime-boost regimen induced robust T cell responses to both HIV-1 and M. tuberculosis. Therefore, proof-of-principle for a dual anti-HIV-1/M. tuberculosis infant vaccine platform is established. Induction of immune responses against these pathogens soon after birth is highly desirable and may provide a basis for lifetime protection maintained by boosts later in life.", "link"=>"http://www.mendeley.com/research/dual-neonate-vaccine-platform-against-hiv1-m-tuberculosis", "reader_count"=>37, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>15, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>15, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>2, "Agricultural and Biological Sciences"=>15, "Medicine and Dentistry"=>10, "Business, Management and Accounting"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/775546"], "description"=>"<p>(<b>A</b>) Groups of 4 BALB/c mice were immunized with\n 10<sup>7</sup> PFU i.m. of either 7.5MVA.HIVA, 7.5MVA.85A or\n sMVA.HIVA.85A, sacrificed 2 weeks later and splenocytes from individual\n mice were analyzed for IFN-γ production following peptide\n stimulation. Data are represented as means ± SD.\n (<b>B–C</b>) Groups of 4 BALB/c mice were immunized i.m.\n with 10<sup>5</sup> PFU of either 7.5MVA.HIVA (triangles), mMVA.HIVA.85A\n (circles) or sMVA.HIVA.85A (squares) vaccines. Two weeks later, mice\n were sacrificed and the ability of splenocytes from individual animals\n to respond to increasing amounts of peptide H was assessed in an\n IFN-γ ELISPOT (<b>B</b>), ICS (<b>C</b>) and <i>in\n vivo</i> killing (<b>D</b>) assays. Mean ± SD are\n shown. Only stimulation with 1 µM H peptide in an IFN-γ\n ELISPOT assay provided a statistically significant difference\n (<i>p</i> = 0.04) between frequencies\n induced using the mH5 and ssp promoters.</p>", "links"=>[], "tags"=>["hiv-1-", "t"], "article_id"=>445915, "categories"=>["Infectious Diseases"], "users"=>["Richard Hopkins", "Anne Bridgeman", "Joan Joseph", "Sarah C. Gilbert", "Helen McShane", "Tomáš Hanke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020067.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_HIV_1_and_M_tuberculosis_specific_T____cell_responses_/445915", "title"=>"Induction of HIV-1- and <i>M. tuberculosis</i>-specific T\n cell responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:28:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/775719"], "description"=>"<p>(<b>A</b>) Groups of 5 BALB/c mice received either\n BCG.HIVA<sup>222</sup> (B<sup>222</sup>) (<b>i</b> and\n <b>vii–ix</b>) or no vaccine (<b>ii–v</b>)\n on week 0, followed by rMVA(s) (<b>ii–ix</b>) as indicated\n on the top of the graphs or no vaccine (<b>i</b>) at week 12. On\n week 16, mice were killed and their HIV-1 (H and II)- and mycobacterium\n (P11, P15 or PPD)-specific responses were determined in an IFN-γ\n ELISPOT assay using MHC class I (H and P11) or class II (II and\n P15)-restricted peptides. Results are shown as individual animal\n responses (black dots) with group means (horizontal bars).\n (<b>B</b>) The functionality of vaccine-induced\n CD8<sup>+</sup> T cell responses was assess in a multicolour\n intracellular cytokine staining assay. The group mean frequencies of\n single-, double- or triple-cytokine-producing H- or P11-specific cells\n following background subtraction are shown for the three regimens\n indicated above the graphs.</p>", "links"=>[], "tags"=>["robust", "hiv-1-", "cells"], "article_id"=>446094, "categories"=>["Infectious Diseases"], "users"=>["Richard Hopkins", "Anne Bridgeman", "Joan Joseph", "Sarah C. Gilbert", "Helen McShane", "Tomáš Hanke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020067.g004", "stats"=>{"downloads"=>4, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_robust_HIV_1_and_M____tuberculosis_specific_T_cells_by_the_BCG_HIVA_222____prime_mMVA_HIVA_85A_boost_regimen_/446094", "title"=>"Induction of robust HIV-1- and <i>M.\n tuberculosis</i>-specific T cells by the BCG.HIVA<sup>222</sup>\n prime - mMVA.HIVA.85A boost regimen.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:29:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/775421"], "description"=>"<p>CEF cells were infected with indicated viruses at MOI 1 for 16 h.\n (<b>A</b>) Cell were stained either for Gag p24 or Pk tag (on\n HIVA and Ag85A) expression as shown above and analyzed under fluorescent\n microscope. Also, the relative levels of protein expression were\n assessed using flow cytometry and shown either as a (<b>B</b>)\n histogram for parental MVA (black), 7.5MVA.HIVA (red), mMVA.HIVA.85A\n (blue) or sMVA.HIVA.85A (green) viruses or (<b>C</b>) expressed as\n mean fluorescent intensity (MFI) ± SD (<b>C</b>). The\n figure shows representative data of three independent experiments.</p>", "links"=>[], "tags"=>["recombinant", "mvas", "cef"], "article_id"=>445795, "categories"=>["Infectious Diseases"], "users"=>["Richard Hopkins", "Anne Bridgeman", "Joan Joseph", "Sarah C. Gilbert", "Helen McShane", "Tomáš Hanke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020067.g002", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_expression_from_recombinant_MVAs_in_CEF_cells_/445795", "title"=>"Protein expression from recombinant MVAs in CEF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:27:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/775287"], "description"=>"<p>Expression cassettes containing genes coding for immunogens HIVA and Ag85\n using either β-galactosidase or GFP markers were inserted into the\n tk locus of the MVA genome by homologous recombination directed by the\n left and right tk flanking regions (tk<sub>L</sub> and tk<sub>R</sub>).\n Transcription of the two immunogens was controlled by either P7.5,\n modified H5 (mH5) or short synthetic (ssp) promoters. In the mH5\n version, the GFP gene is flanked by two homologous repeats (A26L), which\n facilitate removal of the selection marker. Proteins/epitopes are shown\n in bold, while promoters are indicated using a regular font style.</p>", "links"=>[], "tags"=>["inserted", "dna"], "article_id"=>445655, "categories"=>["Infectious Diseases"], "users"=>["Richard Hopkins", "Anne Bridgeman", "Joan Joseph", "Sarah C. Gilbert", "Helen McShane", "Tomáš Hanke"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020067.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_representation_of_inserted_DNA_fragments_/445655", "title"=>"Schematic representation of inserted DNA fragments.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 18:26:36"}

PMC Usage Stats | Further Information

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Relative Metric

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