Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen
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{"title"=>"Tailoring subunit vaccine immunity with adjuvant combinations and delivery routes using the middle east respiratory coronavirus (MERS-CoV) receptor-binding domain as an antigen", "type"=>"journal", "authors"=>[{"first_name"=>"Jiaming", "last_name"=>"Lan", "scopus_author_id"=>"24376550300"}, {"first_name"=>"Yao", "last_name"=>"Deng", "scopus_author_id"=>"36238838100"}, {"first_name"=>"Hong", "last_name"=>"Chen", "scopus_author_id"=>"57050565900"}, {"first_name"=>"Guangwen", "last_name"=>"Lu", "scopus_author_id"=>"35111348400"}, {"first_name"=>"Wen", "last_name"=>"Wang", "scopus_author_id"=>"57189226945"}, {"first_name"=>"Xiaojuan", "last_name"=>"Guo", "scopus_author_id"=>"56431579800"}, {"first_name"=>"Zhuozhuang", "last_name"=>"Lu", "scopus_author_id"=>"8671190200"}, {"first_name"=>"George F.", "last_name"=>"Gao", "scopus_author_id"=>"7403171212"}, {"first_name"=>"Wenjie", "last_name"=>"Tan", "scopus_author_id"=>"7401959748"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"600550423", "sgr"=>"84913534501", "issn"=>"19326203", "pmid"=>"25405618", "scopus"=>"2-s2.0-84913534501", "doi"=>"10.1371/journal.pone.0112602", "isbn"=>"1932-6203"}, "id"=>"c7d220c6-7ecf-3e5a-a89b-18d7c2ae56e2", "abstract"=>"The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund's adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.", "link"=>"http://www.mendeley.com/research/tailoring-subunit-vaccine-immunity-adjuvant-combinations-delivery-routes-using-middle-east-respirato", "reader_count"=>18, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>5, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1798599"], "description"=>"<p>Eight mice per group received three vaccinations with 10 µg of recombinant RBD protein combined with different adjuvants at 3 weeks intervals. Sera were collected at the indicated times to analyze the humoral immune response. Mice were sacrificed 2 weeks after the last immunisation, and the spleen and lungs were harvested.</p>", "links"=>[], "tags"=>["Tailoring Subunit Vaccine Immunity", "alum", "combination", "CpG ODN", "ifa", "ifn", "CpG ODN optimized", "neutralizing antibodies", "Middle East Respiratory Coronavirus", "vaccine", "antibody", "humoral", "subunit vaccination", "balb", "Different vaccination regimens", "delivery routes", "protein", "adjuvant", "vaccination regimen", "immunity", "splenocyte cytokine production", "rbd", "response"], "article_id"=>1245197, "categories"=>["Uncategorised"], "users"=>["Jiaming Lan", "Yao Deng", "Hong Chen", "Guangwen Lu", "Wen Wang", "Xiaojuan Guo", "Zhuozhuang Lu", "George F. Gao", "Wenjie Tan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112602.g002", "stats"=>{"downloads"=>0, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccination_and_analysis_timeline_schematic_/1245197", "title"=>"Vaccination and analysis timeline schematic.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 02:53:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1798598"], "description"=>"<p>A) The location of RBD on the MERS-CoV spike protein. B) SDS-PAGE of purified recombinant RBD protein from a baculovirus expression vector system (BEVS). Lane 1 contains a protein molecular-weight marker, and lane 2 contains purified recombinant RBD protein. C) Western-blot analysis of recombinant RBD protein by a mice polyclonal antibody against spike of MERS-CoV.</p>", "links"=>[], "tags"=>["Tailoring Subunit Vaccine Immunity", "alum", "combination", "CpG ODN", "ifa", "ifn", "CpG ODN optimized", "neutralizing antibodies", "Middle East Respiratory Coronavirus", "vaccine", "antibody", "humoral", "subunit vaccination", "balb", "Different vaccination regimens", "delivery routes", "protein", "adjuvant", "vaccination regimen", "immunity", "splenocyte cytokine production", "rbd", "response"], "article_id"=>1245196, "categories"=>["Uncategorised"], "users"=>["Jiaming Lan", "Yao Deng", "Hong Chen", "Guangwen Lu", "Wen Wang", "Xiaojuan Guo", "Zhuozhuang Lu", "George F. Gao", "Wenjie Tan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112602.g001", "stats"=>{"downloads"=>6, "page_views"=>150, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_the_MERS_CoV_RBD_protein_and_purification_of_recombinant_RBD_protein_/1245196", "title"=>"Schematic of the MERS-CoV RBD protein and purification of recombinant RBD protein.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 02:53:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1798603"], "description"=>"<p>(A) IFN-γ, (B) IL-2, (C) TNF-α, (D) IL-4, (E) IL-6 and (F) IL-10. Statistical significance was defined by *<i>p</i><0.05 and **<i>p</i><0.01. A, alum; C, CpG; P, poly(I:C); I, IFA. Each group contained 8 mice and all experiments repeated for 3 times.</p>", "links"=>[], "tags"=>["Tailoring Subunit Vaccine Immunity", "alum", "combination", "CpG ODN", "ifa", "ifn", "CpG ODN optimized", "neutralizing antibodies", "Middle East Respiratory Coronavirus", "vaccine", "antibody", "humoral", "subunit vaccination", "balb", "Different vaccination regimens", "delivery routes", "protein", "adjuvant", "vaccination regimen", "immunity", "splenocyte cytokine production", "rbd", "response"], "article_id"=>1245201, "categories"=>["Uncategorised"], "users"=>["Jiaming Lan", "Yao Deng", "Hong Chen", "Guangwen Lu", "Wen Wang", "Xiaojuan Guo", "Zhuozhuang Lu", "George F. Gao", "Wenjie Tan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112602.g006", "stats"=>{"downloads"=>4, "page_views"=>101, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytometric_Bead_Assay_CBA_to_determine_the_in_vitro_cytokine_production_of_splenocytes_from_immunised_mice_after_the_third_immunisation_/1245201", "title"=>"Cytometric Bead Assay (CBA) to determine the in vitro cytokine production of splenocytes from immunised mice after the third immunisation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 02:53:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1798601"], "description"=>"<p>Heat-inactived sera after the third vaccination were used for the detection of the neutralization antibodies by MERS-CoV pseudovirus system. Neutralization titres were calculated when the relative inhibition rate was higher than 50%. Data are presented as means with standard error of the mean (SEM). Statistical significance was defined as **<i>p</i><0.01. A, alum; C, CpG; P, poly(I:C); I, IFA. Each group contained 8 mice and all experiments repeated for 3 times.</p>", "links"=>[], "tags"=>["Tailoring Subunit Vaccine Immunity", "alum", "combination", "CpG ODN", "ifa", "ifn", "CpG ODN optimized", "neutralizing antibodies", "Middle East Respiratory Coronavirus", "vaccine", "antibody", "humoral", "subunit vaccination", "balb", "Different vaccination regimens", "delivery routes", "protein", "adjuvant", "vaccination regimen", "immunity", "splenocyte cytokine production", "rbd", "response"], "article_id"=>1245199, "categories"=>["Uncategorised"], "users"=>["Jiaming Lan", "Yao Deng", "Hong Chen", "Guangwen Lu", "Wen Wang", "Xiaojuan Guo", "Zhuozhuang Lu", "George F. Gao", "Wenjie Tan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112602.g004", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_neutralization_antibody_responses_induced_in_the_immunized_mice_/1245199", "title"=>"The neutralization antibody responses induced in the immunized mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 02:53:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1798602"], "description"=>"<p>Lymphocytes were isolated 2 weeks after the third immunisation. Data are expressed as spot-forming cells (SFC) responding to RBD-specific peptides and presented as means with a standard error of the mean (SEM). Significant values between the vaccinated groups are defined by *<i>p</i><0.05 and **<i>p</i><0.01. Lymphocytes from the spleen (A) and lung (B) of the immunised mice. A, alum; C, CpG; P, poly(I:C); I, IFA. Each group contained 8 mice and all experiments repeated for 3 times.</p>", "links"=>[], "tags"=>["Tailoring Subunit Vaccine Immunity", "alum", "combination", "CpG ODN", "ifa", "ifn", "CpG ODN optimized", "neutralizing antibodies", "Middle East Respiratory Coronavirus", "vaccine", "antibody", "humoral", "subunit vaccination", "balb", "Different vaccination regimens", "delivery routes", "protein", "adjuvant", "vaccination regimen", "immunity", "splenocyte cytokine production", "rbd", "response"], "article_id"=>1245200, "categories"=>["Uncategorised"], "users"=>["Jiaming Lan", "Yao Deng", "Hong Chen", "Guangwen Lu", "Wen Wang", "Xiaojuan Guo", "Zhuozhuang Lu", "George F. Gao", "Wenjie Tan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112602.g005", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ELISpot_analysis_of_splenocyte_and_pulmonary_lymphocyte_IFN_947_secretion_/1245200", "title"=>"ELISpot analysis of splenocyte and pulmonary lymphocyte IFN-γ secretion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 02:53:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1798600"], "description"=>"<p>A) Total RBD-specific IgG titres were determined by ELISA 2 weeks after the second and third immunisations. B) NaSCN-displacement ELISA to measure the avidity of RBD-specific IgG 2 weeks after the third immunisation. Median displacement is shown for each group against an increasing concentration of NaSCN. The level of NaSCN required to displace 50% of the IgG is indicated. C, D, E and F) Total IgG1, IgG2a and IgG2b RBD-specific titres were determined by ELISA 2 weeks after the third immunisation. Each group contained 8 mice and all experiments repeated for 3 times.</p>", "links"=>[], "tags"=>["Tailoring Subunit Vaccine Immunity", "alum", "combination", "CpG ODN", "ifa", "ifn", "CpG ODN optimized", "neutralizing antibodies", "Middle East Respiratory Coronavirus", "vaccine", "antibody", "humoral", "subunit vaccination", "balb", "Different vaccination regimens", "delivery routes", "protein", "adjuvant", "vaccination regimen", "immunity", "splenocyte cytokine production", "rbd", "response"], "article_id"=>1245198, "categories"=>["Uncategorised"], "users"=>["Jiaming Lan", "Yao Deng", "Hong Chen", "Guangwen Lu", "Wen Wang", "Xiaojuan Guo", "Zhuozhuang Lu", "George F. Gao", "Wenjie Tan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112602.g003", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RBD_specific_antibody_response_in_immunised_mice_/1245198", "title"=>"RBD-specific antibody response in immunised mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-18 02:53:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1798604"], "description"=>"<p>A*, Aluminium hydroxide; P*, poly(I:C); C*, CpG; I*, IFA.</p><p>Vaccination groups and seroconversion after the first and the second immunization.</p>", "links"=>[], "tags"=>["Tailoring Subunit Vaccine Immunity", "alum", "combination", "CpG ODN", "ifa", "ifn", "CpG ODN optimized", "neutralizing antibodies", "Middle East Respiratory Coronavirus", "vaccine", "antibody", "humoral", "subunit vaccination", "balb", "Different vaccination regimens", "delivery routes", "protein", "adjuvant", "vaccination regimen", "immunity", "splenocyte cytokine production", "rbd", "response"], "article_id"=>1245202, "categories"=>["Uncategorised"], "users"=>["Jiaming Lan", "Yao Deng", "Hong Chen", "Guangwen Lu", "Wen Wang", "Xiaojuan Guo", "Zhuozhuang Lu", "George F. Gao", "Wenjie Tan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0112602.t001", "stats"=>{"downloads"=>4, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccination_groups_and_seroconversion_after_the_first_and_the_second_immunization_/1245202", "title"=>"Vaccination groups and seroconversion after the first and the second immunization.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-18 02:53:26"}

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Relative Metric

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