Pre-Clinical Evaluation of a Novel Nanoemulsion-Based Hepatitis B Mucosal Vaccine
Publication Date
August 13, 2008
Journal
PLOS ONE
Authors
Paul E. Makidon, Anna U. Bielinska, Shraddha S. Nigavekar, Katarzyna W. Janczak, et al
Volume
3
Issue
8
Pages
e2954
DOI
https://dx.plos.org/10.1371/journal.pone.0002954
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0002954
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/18698426
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2496893
Europe PMC
http://europepmc.org/abstract/MED/18698426
Web of Science
000264412600040
Scopus
51649091684
Mendeley
http://www.mendeley.com/research/preclinical-evaluation-novel-nanoemulsionbased-hepatitis-b-mucosal-vaccine
Events
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Mendeley | Further Information

{"title"=>"Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine", "type"=>"journal", "authors"=>[{"first_name"=>"Paul E.", "last_name"=>"Makidon", "scopus_author_id"=>"12761984900"}, {"first_name"=>"Anna U.", "last_name"=>"Bielinska", "scopus_author_id"=>"6603831162"}, {"first_name"=>"Shraddha S.", "last_name"=>"Nigavekar", "scopus_author_id"=>"6508109115"}, {"first_name"=>"Katarzyna W.", "last_name"=>"Janczak", "scopus_author_id"=>"8440445500"}, {"first_name"=>"Jessica", "last_name"=>"Knowlton", "scopus_author_id"=>"6603806828"}, {"first_name"=>"Alison J.", "last_name"=>"Scott", "scopus_author_id"=>"56322134700"}, {"first_name"=>"Nicholas", "last_name"=>"Mank", "scopus_author_id"=>"24781135400"}, {"first_name"=>"Zhengyi", "last_name"=>"Cao", "scopus_author_id"=>"7402432298"}, {"first_name"=>"Sivaprakash", "last_name"=>"Rathinavelu", "scopus_author_id"=>"6507667549"}, {"first_name"=>"Michael R.", "last_name"=>"Beer", "scopus_author_id"=>"15827494500"}, {"first_name"=>"J. Erby", "last_name"=>"Wilkinson", "scopus_author_id"=>"7103230055"}, {"first_name"=>"Luz P.", "last_name"=>"Blanco", "scopus_author_id"=>"36753212500"}, {"first_name"=>"Jeffrey J.", "last_name"=>"Landers", "scopus_author_id"=>"7103347086"}, {"first_name"=>"James R.", "last_name"=>"Baker", "scopus_author_id"=>"7404128072"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"352335555", "sgr"=>"51649091684", "doi"=>"10.1371/journal.pone.0002954", "scopus"=>"2-s2.0-51649091684", "isbn"=>"1932-6203", "pmid"=>"18698426"}, "id"=>"15c421d8-1562-3beb-bb72-ea3d1c98acec", "abstract"=>"Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations.|Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm) associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6) titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu). Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2) subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.|Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability of this vaccine formulation at elevated temperatures suggests a direct advantage in the field, since potential excursions from cold chain maintenance could be tolerated without a loss in therapeutic efficacy.", "link"=>"http://www.mendeley.com/research/preclinical-evaluation-novel-nanoemulsionbased-hepatitis-b-mucosal-vaccine", "reader_count"=>44, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>3, "Other"=>4, "Student > Master"=>7, "Student > Bachelor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>11, "Student > Doctoral Student"=>1, "Student > Ph. D. 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CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/923992"], "description"=>"<p>Silver stained SDS-PAGE: Analysis of freshly prepared vs. 72 hour incubated HBs antigen mixed with 20% NE (A). Conditions of the incubation are specified above the gel. HBsAg monomer and dimer are indicated with arrows at 24 kDa and 48 kDa bands. Western blot: The protein configuration is identical to as described for SDS-PAGE (B). HBsAg is detected using a polyclonal anti-HBsAg antibody for all incubation conditions.</p>", "links"=>[], "tags"=>["biochemistry/drug discovery", "biochemistry/protein chemistry", "immunology/antigen processing and recognition", "immunology/immune response", "immunology/innate immunity", "virology/vaccines", "infectious diseases/epidemiology and control of infectious diseases", "infectious diseases/viral infections", "pathology/histopathology", "pathology/immunology"], "article_id"=>594413, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stability_of_HBsAg_/594413", "title"=>"Stability of HBsAg.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:44:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/924671"], "description"=>"<p>The comparison of HBsAg-NE stored at test temperature conditions to freshly prepared formulation using SDS-PAGE followed by silver staining (S) or Western immunoblotting (W) is shown. Lanes are labeled according to sample storage conditions as follows- 1: fresh, 2: 4°C, 3: 25°C and 4: 40°C. Samples were stored for (A) 6 weeks, (B) 6 months (24 weeks), or (C) 1 year (52 weeks) at the three test temperatures. Each lane contains 0.5 μg of antigen. Arrow indicates the HBsAg major band. (D) Particle size comparison of NE alone to freshly mixed HBsAg-NE and formulation stored up to a year. Mean diameter of particles is shown in microns +/− SD.</p>", "links"=>[], "tags"=>["vitro", "hbsag-ne"], "article_id"=>595102, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_analyses_of_HBsAg_NE_stability_/595102", "title"=>"In vitro analyses of HBsAg-NE stability.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:48:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/924583"], "description"=>"<p>Rats and guinea pigs were immunized intranasally with either 5 μg or 20 μg HBsAg mixed with 20% NE. Serum anti-HBsAg IgG antibody concentrations are presented as mean of endpoint titers in individual sera±SEM. Data represents anti-HBsAg end titers measured 3 weeks after a single dose (1 dose) vaccination and after two vaccinations (2 doses) measured at 7 weeks.</p>", "links"=>[], "tags"=>["rats", "guinea"], "article_id"=>595020, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunogenicity_in_rats_and_guinea_pigs_/595020", "title"=>"Immunogenicity in rats and guinea pigs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:48:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/925012"], "description"=>"<p>Mice: CD-1 mice were vaccinated with HBsAg-NE and primed at 2 weeks. (A–B) Photomicrographs of H&E stained nasal epithelium collected from mice 14 days following the boost vaccination. Only normal tissue architecture was recorded which indicates a lack of (sub) chronic cytotoxicity or inflammation. (C) Nasal epithelium collected 24 hours following boost vaccination with HBsAg-NE scored as a +1 grade change according to methodology as described is shown as an example of architectural change. The arrow indicates a single microscopic focus of accumulation of mucoid material and debris in the nasal passages. However, no evidence of epithelial necrosis or inflammatory infiltration of the nasal epithelium is detected. (D) Nasal epithelium collected 24 hours following boost vaccination with HBsAg-NE scored as a +2 grade. The arrow indicates a single microscopic focus of accumulation of mucoid material and debris in the nasal passages in the absence of inflammatory changes. Architectural change demonstrated in C and D are considered incidental and can be observed in non-vaccinated mice. Rats and guinea pigs: Nasal epithelium was collected 14 days following final boost vaccination from rats (E–F) and guinea pigs (G–H) treated a total of 3 doses of HBsAg-NE administered 14 days apart. Normal tissue architecture is observed suggesting lack of toxicity or inflammation. Dogs: Nasal biopsies were collected 24 hours following the final dose in dogs treated with a total of three doses of NE adjuvant. NE was delivered using a Pfeiffer multidose wide angle sprayer pump in 200 μl/dose (I) or 400 μl/dose (J). No evidence of inflammation or cytotoxicity was detected.</p>", "links"=>[], "tags"=>["nasal", "exposed", "ne", "adjuvant"], "article_id"=>595437, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g009", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathological_analysis_of_nasal_tissue_exposed_to_NE_adjuvant_or_HBsAg_NE_/595437", "title"=>"Histopathological analysis of nasal tissue exposed to NE adjuvant or HBsAg-NE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:50:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/925134"], "description"=>"<p>Average particle size 349 (+/−17); Mean (+/−SD).</p>", "links"=>[], "tags"=>["nanoemulsion"], "article_id"=>595572, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.t001", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Consistency_of_nanoemulsion_particle_size_/595572", "title"=>"Consistency of nanoemulsion particle size.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 09:51:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/924161"], "description"=>"<p>Zeta potential: (A) The zeta potential was measured for HBsAg (2.5 mg/ml), 20% NE and mixture of HBsAg with NE (HBsAg-NE) in water and PBS. Surface charge is reported in mV units. Particle sizing: Size distribution was measured using a laser diffraction particle-sizer. Analysis of HBsAg alone (B), NE alone (C), and NE with 10 μg/ml of HBsAg (D). Data was processed and analyzed using Fraunhofer optical modeling and number weighted averaging (number %). Single population intensity peaks indicate monodisperse populations of HBsAg (28 nm), NE (349 nm), and HBsAg-NE (335 nm). Calorimetric titration of HBsAg with NE: 25 injections of 1% NE (10 μl/injection) were introduced into a sample cell containing HBsAg (600 μg/ml in PBS) at 30°C. The upper panel shows differences between the sample and reference cell containing PBS. The lower panel shows enthalpy per injection of NE injected versus injection number. An exothermic reaction was measured following the addition of nanoemulsion to an antigen solution. Addition of nanoemulsion to the antigen solution became less energetic as the total concentration of nanoemulsion increased, suggesting that the antigen was being depleted. ΔCp was calculated to be −1.44 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002954#pone.0002954-5\" target=\"_blank\">[77]</a>.</p>", "links"=>[], "tags"=>["ne"], "article_id"=>594590, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g002", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HBsAg_interaction_with_NE_droplets_/594590", "title"=>"HBsAg interaction with NE droplets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:45:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/924791"], "description"=>"<p>HBsAg specific antibody responses to freshly prepared HBsAg-NE or HBsAg-NE stored under real-time (4°C), accelerated (25°C) and stressed (40°C) temperature conditions are depicted. CD-1 mice were vaccinated with either freshly prepared or stored HBsAg-NE and boosted at 6 weeks. Serum anti-HBsAg IgG antibody concentrations are presented as a mean of endpoint titers in individual sera +/− SD. Comparison of serum IgG elicited by freshly prepared HBsAg-NE to formulation stored for (A) 6 weeks, (B) 3 months, (C) 6 months or (D) 1 year at indicated temperatures. * indicates a statistical difference (<i>p value<0.05</i>) in the anti-HBsAg IgG titers between freshly mixed and stored formulation. Arrows indicate vaccine administration.</p>", "links"=>[], "tags"=>["vivo", "hbsag-ne"], "article_id"=>595228, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g008", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_analyses_of_HBsAg_NE_stability_/595228", "title"=>"In vivo analyses of HBsAg-NE stability.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:49:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/925186"], "description"=>"a<p>- The number of animals used for analysis: CD-1 (n = 10), BALB/c, Wistar rats and Hartley guinea pigs (n = 5) and Beagles (n = 1) per group.</p>b<p>- Histological lesions were evaluated on a scale from 0 to 10 with +1 single microscopic focus, +2 at least 2 microscopic foci, +3 more than 3 foci or multiple locally extensive areas of pathology, +4 to +6 were associated increasing severity and more extensive distribution (these lesions could be associated with morbidity), +7 and above had increasing degrees of inflammation (+10 associated with mortality).</p>c<p>- Other tissues evaluated include heart, liver, kidneys, spleen, esophagus, trachea, stomach, intestines, pancreas, and adrenals.</p>d<p>- Metabolic analysis evaluated by standard biochemical serum profile analysis on a IDEXX Vet Test Analyzer™ and performed at the Animal Diagnostic Laboratory through the Unit for Laboratory Animal Medicine at the University of Michigan. Normal indicates all analytes fell within normal expected distributions per species.</p>e<p>- Administered every 2 weeks.</p>f<p>- Administered every 15 minutes.</p>g<p>- Administered every 4 hours.</p>h<p>- Administered every 4 weeks.</p>", "links"=>[], "tags"=>["toxicology"], "article_id"=>595621, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.t002", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pre_clinical_toxicology_evaluation_/595621", "title"=>"Pre-clinical toxicology evaluation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 09:51:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/924249"], "description"=>"<p>Effect of NE adjuvant: Mice were immunized intranasally with HBsAg-NE consisting of 20 μg of HBsAg mixed with 0% to 40% concentrations of NE (A). Significant statistical difference with <i>p value<0.05</i> was observed between all HBsAg-NE formulations and HBsAg-PBS vaccine. Antigen dose escalation: Mice were immunized intranasally with 1 μg to 40 μg HBsAg mixed with 20% NE (B). A significant statistical difference with <i>p value<0.05</i> was observed between all 5 μg to 40 μg HBsAg-NE formulations and 1 μg HBsAg-NE vaccine. Serum anti-HBsAg IgG antibody concentrations are presented as mean of endpoint titers in individual sera +/− SEM. * indicates a statistical difference (<i>p value<0.05</i>) in the anti-HBsAg IgG titers. Arrows indicate vaccine administration.</p>", "links"=>[], "tags"=>["igg"], "article_id"=>594684, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Development_of_IgG_response_in_serum_/594684", "title"=>"Development of IgG response in serum.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:46:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/924470"], "description"=>"<p>Mucosal antibody measurements were performed in BAL fluids obtained 23 weeks after i.n immunization with HBsAg-NE vaccines. IgA detection: The anti-HBsAg IgA detection was performed with 1:2 dilutions of BAL (A). Results are presented as mean values of OD at 405 nm +/−SEM. IgG detection: The anti-HBsAg IgG antibody concentrations are presented as end point titers (B). Antigen-specific cytokine expression. Pattern of Th1 (IFN-γ and TNF-α) and Th2 (IL-4, IL-5 and IL-10) cytokine expression in vitro in splenocytes from mice intranasally immunized with HBsAg-NE (C). Splenocytes were obtained at 23 weeks after initial immunization from mice with HBsAg-20% NE. Results are presented as fold increase of the cytokine production over levels detected in non-stimulated splenocyte cultures.</p>", "links"=>[], "tags"=>["mucosal", "cellular", "responses"], "article_id"=>594902, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g005", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_immune_response_mucosal_and_cellular_responses_to_HBsAg_NE_/594902", "title"=>"Characterization of immune response mucosal and cellular responses to HBsAg-NE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:47:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/924340"], "description"=>"<p>Time course of antibody response: Mice were immunized with 20 μg HBsAg. Antigen was mixed with 20% NE for intranasal administration (HBsAg-NE), or adsorbed on aluminum hydroxide (HBsAg-Alu) for intramuscular injections (A). Serum anti-HBsAg IgG antibody concentrations are presented as mean of endpoint titers in individual sera +/− SEM. * indicates a statistical difference (<i>p value<0.05</i>) in the anti-HBsAg IgG titers. Arrows indicate vaccine administration. Avidity of anti-HBsAg IgG: Analysis of sera from mice immunized i.n. with HBsAg-NE and with i.m. injections of HBsAg-Alu vaccines (B). Avidity indexes (AI) were assessed using 1.5 M NaSCN as a discriminating salt concentration. Each circle represents individual AI and lines indicate mean AI value for each group obtained in two independent assays. Serum anti-HBsAg IgG subclass: Anti-HBsAg IgG subclass pattern in mice immunized nasally with HBsAg-NE and injected i.m. with HBsAg-Alu vaccine (C). Analysis of sera collected at 22 weeks after initial immunization. The results are presented as ratio of the specific subclass IgG to the overall IgG titer. * indicates statistical difference (<i>p value<0.05</i>) between NE-based and alum-based immunizations.</p>", "links"=>[], "tags"=>["mucosal", "ne-based", "aluminum-based", "injectible", "hbsag"], "article_id"=>594765, "categories"=>["Immunology", "Biochemistry", "Infectious Diseases", "Medicine"], "users"=>["Paul E. Makidon", "Anna U. Bielinska", "Shraddha S. Nigavekar", "Katarzyna W. Janczak", "Jessica Knowlton", "Alison J. Scott", "Nicholas Mank", "Zhengyi Cao", "Sivaprakash Rathinavelu", "Michael R. Beer", "J. Erby Wilkinson", "Luz P. Blanco", "Jeffrey J. Landers", "James R. Baker Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002954.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_mucosal_NE_based_with_conventional_aluminum_based_injectible_HBsAg_vaccine_/594765", "title"=>"Comparison of mucosal NE-based with conventional aluminum-based injectible HBsAg vaccine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 09:46:49"}

PMC Usage Stats | Further Information

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Relative Metric

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