Immunization with Cholera Toxin B Subunit Induces High-Level Protection in the Suckling Mouse Model of Cholera
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{"title"=>"Immunization with Cholera Toxin B Subunit Induces High-Level Protection in the Suckling Mouse Model of Cholera", "type"=>"journal", "authors"=>[{"first_name"=>"Gregory A.", "last_name"=>"Price", "scopus_author_id"=>"7201598557"}, {"first_name"=>"Kim", "last_name"=>"McFann", "scopus_author_id"=>"13102828700"}, {"first_name"=>"Randall K.", "last_name"=>"Holmes", "scopus_author_id"=>"7402012636"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"368446772", "sgr"=>"84874517872", "doi"=>"10.1371/journal.pone.0057269", "scopus"=>"2-s2.0-84874517872", "pmid"=>"23468950"}, "id"=>"a2f3fb42-4d0c-34e1-afab-bed286e07735", "abstract"=>"Cholera toxin (CT) is the primary virulence factor responsible for severe cholera. Vibrio cholerae strains unable to produce CT show severe attenuation of virulence in animals and humans. The pentameric B subunit of CT (CTB) contains the immunodominant epitopes recognized by antibodies that neutralize CT. Although CTB is a potent immunogen and a promising protective vaccine antigen in animal models, immunization of humans with detoxified CT failed to protect against cholera. We recently demonstrated however that pups reared from mice immunized intraperitoneally (IP) with 3 doses of recombinant CTB were well protected against a highly lethal challenge dose of V. cholerae N16961. The present study investigated how the route and number of immunizations with CTB could influence protective efficacy in the suckling mouse model of cholera. To this end female mice were immunized with CTB intranasally (IN), IP, and subcutaneously (SC). Serum and fecal extracts were analyzed for anti-CTB antibodies by quantitative ELISA, and pups born to immunized mothers were challenged orogastrically with a lethal dose of V. cholerae. Pups from all immunized groups were highly protected from death by 48 hours (64-100% survival). Cox regression showed that percent body weight loss at 24 hours predicted death by 48 hours, but we were unable to validate a specific amount of weight loss as a surrogate marker for protection. Although CTB was highly protective in all regimens, three parenteral immunizations showed trends toward higher survival and less weight loss at 24 hours post infection. These results demonstrate that immunization with CTB by any of several routes and dosing regimens can provide protection against live V. cholerae challenge in the suckling mouse model of cholera. Our data extend the results of previous studies and provide additional support for the inclusion of CTB in the development of a subunit vaccine against V. cholerae.", "link"=>"http://www.mendeley.com/research/immunization-cholera-toxin-b-subunit-induces-highlevel-protection-suckling-mouse-model-cholera", "reader_count"=>12, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>1, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>1, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>4, "Immunology and Microbiology"=>2, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/974643"], "description"=>"<p>Each symbol represents the serum anti-CTB antibody concentration for an individual mouse. The horizontal lines represent the geometric mean concentration per group (<i>n</i> = 5). Statistical differences between groups were analyzed using ANOVA with Tukey-Kramer post-test analysis (# P<0.001 and *P<0.05 versus the CTB/IP1X group).</p>", "links"=>[], "tags"=>["ctb-specific", "igg", "concentrations", "14", "days", "immunization", "intranasal", "subcutaneous", "intraperitoneal"], "article_id"=>642603, "categories"=>["Microbiology", "Biotechnology", "Infectious Diseases", "Immunology"], "users"=>["Gregory A. Price", "Kim McFann", "Randall K. Holmes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057269.g002", "stats"=>{"downloads"=>0, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_CTB_specific_IgG_concentrations_at_14_days_following_the_final_only_immunization_via_the_intranasal_IN_subcutaneous_SC_or_intraperitoneal_IP_route_/642603", "title"=>"Serum CTB-specific IgG concentrations at 14 days following the final/only immunization via the intranasal (IN), subcutaneous (SC), or intraperitoneal (IP) route.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 14:27:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/974644"], "description"=>"<p>For each fecal extract, the relative abundance of CTB-specific IgA is expressed as a percentage of the total IgA in that fecal extract. Each symbol represents an individual mouse, and horizontal bars represent the geometric mean for that group (<i>n</i> = 5). Statistical differences between groups were analyzed using ANOVA with Tukey-Kramer post-test analysis (# P<0.001 versus all other groups).</p>", "links"=>[], "tags"=>["abundance", "fecal", "ctb-specific", "iga", "14", "days", "immunization", "intranasal", "subcutaneous", "intraperitoneal"], "article_id"=>642604, "categories"=>["Microbiology", "Biotechnology", "Infectious Diseases", "Immunology"], "users"=>["Gregory A. Price", "Kim McFann", "Randall K. Holmes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057269.g003", "stats"=>{"downloads"=>1, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_abundance_of_fecal_CTB_specific_IgA_at_14_days_following_the_final_only_immunization_via_the_intranasal_IN_subcutaneous_SC_or_intraperitoneal_IP_route_/642604", "title"=>"Relative abundance of fecal CTB-specific IgA at 14 days following the final/only immunization via the intranasal (IN), subcutaneous (SC), or intraperitoneal (IP) route.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 14:27:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/974642"], "description"=>"<p>Immunizations and baseline bleeds/fecal collections were staggered depending on the number of immunizations per group to allow for the final/only immunization(s) to occur on the same day for all groups. All boosts occurred at 14-day intervals, and a final bleed/fecal collection occurred 14 days following the final/initial immunization.</p>", "links"=>[], "tags"=>["immunization"], "article_id"=>642602, "categories"=>["Microbiology", "Biotechnology", "Infectious Diseases", "Immunology"], "users"=>["Gregory A. Price", "Kim McFann", "Randall K. Holmes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057269.g001", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Timeline_of_immunization_and_challenge_experiments_/642602", "title"=>"Timeline of immunization and challenge experiments.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 14:27:02"}

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Relative Metric

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