A Neutralizing Anti-gH/gL Monoclonal Antibody Is Protective in the Guinea Pig Model of Congenital CMV Infection
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{"title"=>"A Neutralizing Anti-gH/gL Monoclonal Antibody Is Protective in the Guinea Pig Model of Congenital CMV Infection", "type"=>"journal", "authors"=>[{"first_name"=>"Marcy R.", "last_name"=>"Auerbach", "scopus_author_id"=>"57197496878"}, {"first_name"=>"Donghong", "last_name"=>"Yan", "scopus_author_id"=>"36483837600"}, {"first_name"=>"Rajesh", "last_name"=>"Vij", "scopus_author_id"=>"41162320400"}, {"first_name"=>"Jo Anne", "last_name"=>"Hongo", "scopus_author_id"=>"6701587334"}, {"first_name"=>"Gerald", "last_name"=>"Nakamura", "scopus_author_id"=>"7005426210"}, {"first_name"=>"Jean Michel", "last_name"=>"Vernes", "scopus_author_id"=>"8739670800"}, {"first_name"=>"Y. Gloria", "last_name"=>"Meng", "scopus_author_id"=>"7202938788"}, {"first_name"=>"Samantha", "last_name"=>"Lein", "scopus_author_id"=>"56178536200"}, {"first_name"=>"Pamela", "last_name"=>"Chan", "scopus_author_id"=>"23034020400"}, {"first_name"=>"Jed", "last_name"=>"Ross", "scopus_author_id"=>"7404965730"}, {"first_name"=>"Richard", "last_name"=>"Carano", "scopus_author_id"=>"6701757446"}, {"first_name"=>"Rong", "last_name"=>"Deng", "scopus_author_id"=>"26537345400"}, {"first_name"=>"Nicholas", "last_name"=>"Lewin-Koh", "scopus_author_id"=>"15741312300"}, {"first_name"=>"Min", "last_name"=>"Xu", "scopus_author_id"=>"55636694400"}, {"first_name"=>"Becket", "last_name"=>"Feierbach", "scopus_author_id"=>"6508214956"}], "year"=>2014, "source"=>"PLoS Pathogens", "identifiers"=>{"scopus"=>"2-s2.0-84901311908", "pui"=>"373162938", "pmid"=>"24722349", "issn"=>"15537374", "doi"=>"10.1371/journal.ppat.1004060", "sgr"=>"84901311908"}, "id"=>"8b480917-a881-3cf4-b38f-d163ef3d8895", "abstract"=>"Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection. Congenital HCMV infection occurs in 0.2-1% of all births, and causes birth defects and developmental abnormalities, including sensorineural hearing loss and developmental delay. Several key studies have established the guinea pig as a tractable model for the study of congenital HCMV infection and have shown that polyclonal antibodies can be protective. In this study, we demonstrate that an anti-guinea pig CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing monoclonal antibody protects against fetal infection and loss in the guinea pig. Furthermore, we have delineated the kinetics of GPCMV congenital infection, from maternal infection (salivary glands, seroconversion, placenta) to fetal infection (fetus and amniotic fluid). Our studies support the hypothesis that a neutralizing monoclonal antibody targeting an envelope GPCMV glycoprotein can protect the fetus from infection and may shed light on the therapeutic intervention of HCMV congenital infection in humans.", "link"=>"http://www.mendeley.com/research/neutralizing-antighgl-monoclonal-antibody-protective-guinea-pig-model-congenital-cmv-infection", "reader_count"=>15, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>2, "Psychology"=>2, "Social Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"France"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1460547"], "description"=>"A<p>Pregnant guinea pigs were infected with 4×10<sup>3</sup> PFU of IVP8 at the start of the 2<sup>nd</sup> trimester.</p>B<p>Cumulative results at 21 days post-infection.</p>C<p>Virus detected by quantitative PCR.</p>D<p>Virus detected by nested PCR.</p>E<p>Antibody administered I.P. one day prior to infection at 8 mg/kg dose and then twice per week for 3 weeks with a total of six doses (see <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004060#ppat-1004060-g005\" target=\"_blank\">Figure 5</a> for study scheme).</p>F<p>n/a, not applicable, no fetuses were alive at end of study.</p>G<p>Averaged in-house historical data from infected pregnant guinea pigs without antibody treatment.</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "antibody", "maternal", "congenital", "gpcmv"], "article_id"=>995840, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.t004", "stats"=>{"downloads"=>8, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_1968_GPFc_antibody_on_maternal_mortality_and_congenital_GPCMV_infection_A_B_/995840", "title"=>"Effect of 1968/GPFc antibody on maternal mortality and congenital GPCMV infection<sup>A</sup><sup>B</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460545"], "description"=>"A<p>SG, salivary glands from pregnant dams.</p>B<p>NAb, dam's neutralizing antibody titer, expressed as serum dilution determined by qPCR.</p>C<p>virus detected by qPCR.</p>D<p>virus detected by nested PCR.</p>E<p>AF, amniotic fluid.</p>F<p>ND, not done.</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "kinetics", "gpcmv", "congenital"], "article_id"=>995838, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.t002", "stats"=>{"downloads"=>3, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Viral_kinetics_of_GPCMV_during_congenital_infection_/995838", "title"=>"Viral kinetics of GPCMV during congenital infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460541"], "description"=>"<p>(A) Schematic of mouse 1968, chimeric guinea pig-mouse 1968/GPFc, and chimeric guinea pig-mouse anti-gp120 negative control antibodies. The chimeric antibodies are comprised of a guinea pig Fc and a partial variable region from guinea pig IgG2 (red) and the mouse 1968 partial Fab, containing the antigen-binding site (black) or the anti-gp120 partial Fab, containing the antigen-binding site (blue). (B) Neutralization profiles of mouse 1968, chimeric 1968/GPFc, and chimeric anti-gp120 antibodies on primary guinea pig fibroblasts and endothelial cells. Data from two independent experiments are graphed using a non-linear regression analysis for calculating EC50 values. Concentration of monoclonal antibody is provided in µg/ml. (C) Mouse 1968, chimeric 1968/GPFc, chimeric anti-gp120 antibodies or guinea pig polyclonal IgG were analyzed for their ability to bind to soluble guinea pig FcRn/β2-microglobulin complex by Octet Red QK Instrument.</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "1968", "monoclonal"], "article_id"=>995835, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chimerization_of_the_mouse_1968_monoclonal_antibody_/995835", "title"=>"Chimerization of the mouse 1968 monoclonal antibody.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460554", "https://ndownloader.figshare.com/files/1460555", "https://ndownloader.figshare.com/files/1460556", "https://ndownloader.figshare.com/files/1460557", "https://ndownloader.figshare.com/files/1460558"], "description"=>"<div><p>Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection. Congenital HCMV infection occurs in 0.2–1% of all births, and causes birth defects and developmental abnormalities, including sensorineural hearing loss and developmental delay. Several key studies have established the guinea pig as a tractable model for the study of congenital HCMV infection and have shown that polyclonal antibodies can be protective <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004060#ppat.1004060-Bratcher1\" target=\"_blank\">[1]</a>–<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004060#ppat.1004060-Chatterjee1\" target=\"_blank\">[3]</a>. In this study, we demonstrate that an anti-guinea pig CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing monoclonal antibody protects against fetal infection and loss in the guinea pig. Furthermore, we have delineated the kinetics of GPCMV congenital infection, from maternal infection (salivary glands, seroconversion, placenta) to fetal infection (fetus and amniotic fluid). Our studies support the hypothesis that a neutralizing monoclonal antibody targeting an envelope GPCMV glycoprotein can protect the fetus from infection and may shed light on the therapeutic intervention of HCMV congenital infection in humans.</p></div>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "neutralizing", "monoclonal", "antibody", "guinea", "congenital", "cmv"], "article_id"=>995847, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1004060.s001", "https://dx.doi.org/10.1371/journal.ppat.1004060.s002", "https://dx.doi.org/10.1371/journal.ppat.1004060.s003", "https://dx.doi.org/10.1371/journal.ppat.1004060.s004", "https://dx.doi.org/10.1371/journal.ppat.1004060.s005"], "stats"=>{"downloads"=>16, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Neutralizing_Anti_gH_gL_Monoclonal_Antibody_Is_Protective_in_the_Guinea_Pig_Model_of_Congenital_CMV_Infection_/995847", "title"=>"A Neutralizing Anti-gH/gL Monoclonal Antibody Is Protective in the Guinea Pig Model of Congenital CMV Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460544"], "description"=>"A<p>Fetal loss data is only from surviving dams.</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "fetal", "gpcmv-infected", "guinea"], "article_id"=>995837, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Maternal_mortality_and_fetal_loss_in_GPCMV_infected_guinea_pigs_/995837", "title"=>"Maternal mortality and fetal loss in GPCMV-infected guinea pigs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460543"], "description"=>"<p>15 GPCMV-free, timed pregnant guinea pigs were inoculated by subcutaneous injection with 4×10<sup>3</sup> PFU of IVP8 stock at 21 days gestation. 1968/GPFc and control anti-gp120 antibodies were administered I.P. to 7 and 8 guinea pigs, respectively. The first dose was given one day prior to infection and then twice per week for 3 weeks at 8 mg/kg dose for a total of 6 doses. At day 21 post-infection, guinea pigs were sacrificed and viral infection was determined by PCR from the placenta, fetus, and maternal salivary glands.</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "prophylactic"], "article_id"=>995836, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.g005", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_for_the_anti_gH_gL_prophylactic_protection_study_/995836", "title"=>"Schematic for the anti-gH/gL prophylactic protection study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460531"], "description"=>"<p>43 pregnant guinea pigs were inoculated by subcutaneous injection with 4×10<sup>3</sup> PFU of pathogenic stock IVP8 at day 21 gestation and sacrificed at 1, 3, 7, 11, 15, and 21 days post-infection. Each glyph represents an infected mother with the size of the glyph proportional to the number of infected placentas and/or fetuses recovered. The proportion of infected placentas (x-axis) and infected fetuses (y-axis) was determined by qPCR and nested PCR, respectively. Data was compiled from three separate experiments.</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "placental", "fetal", "21"], "article_id"=>995833, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Temporal_relationship_between_placental_and_fetal_infection_over_21_days_/995833", "title"=>"Temporal relationship between placental and fetal infection over 21 days.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460529"], "description"=>"<p>An antigen-based ELISA assay was used to monitor the anti-gB (A) or anti-gH/gL (B) IgG response in infected pregnant guinea pigs over 21 days. Two dilutions (1∶100- green, 1∶2700- purple) are graphed to display the range of reactivity of the anti-gB response. The positive control, day 12 positive serum, (1∶2700- red, average value from 5 different plates with 2 replicates per plate) consistently resulted in the linear range and near the middle of the dynamic range. Pre-immune samples were consistently at zero indicating the cut-off of the assay (an example is shown at d0 at 1∶100, blue). The 1∶2700 was not graphed for anti-gH/gL (B) due to lack of signal. The error bars represent standard deviation of the means calculated from the results of several animals at each time point (see methods for study details).</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases"], "article_id"=>995831, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Determination_of_the_timing_of_seroconversion_/995831", "title"=>"Determination of the timing of seroconversion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460530"], "description"=>"<p>43 pregnant guinea pigs were inoculated by subcutaneous injection with 4×10<sup>3</sup> PFU of pathogenic stock IVP8 at day 21 gestation and sacrificed at 1, 3, 7, 11, 15, and 21 days post-infection. Each glyph (dot) represents the proportion of infected fetuses, with the size of the glyph proportional to the litter size. The solid lines represent the proportion of infected fetuses in a litter from a beta-binomial model fit to all three cohorts. The dashed segment of each line is extrapolated beyond the cohort data and is model based. See statistical section in methods for more details.</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "kinetics", "fetal", "21", "days", "plotted"], "article_id"=>995832, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.g002", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Viral_kinetics_of_fetal_infection_over_21_days_plotted_from_three_separate_studies_/995832", "title"=>"Viral kinetics of fetal infection over 21 days plotted from three separate studies.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-10 04:47:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1460546"], "description"=>"A<p>ELISA performed with soluble proteins; gB, gH/gL, gH/gL/gO and Pentamer = gH/gL/GP129/GP131/GP133.</p>B<p>Expression of gH/gL protein on the surface of 293T cells.</p>C<p>Antibody neutralizing potency as determined by the anti-gB immunofluorescence method.</p>D<p>Soluble gH/gL protein was used as immunogen.</p>", "links"=>[], "tags"=>["microbiology", "Infectious diseases", "monoclonal", "antibodies"], "article_id"=>995839, "categories"=>["Biological Sciences"], "users"=>["Marcy R. Auerbach", "Donghong Yan", "Rajesh Vij", "Jo-Anne Hongo", "Gerald Nakamura", "Jean-Michel Vernes", "Y. Gloria Meng", "Samantha Lein", "Pamela Chan", "Jed Ross", "Richard Carano", "Rong Deng", "Nicholas Lewin-Koh", "Min Xu", "Becket Feierbach"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004060.t003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_mouse_monoclonal_antibodies_against_GPCMV_/995839", "title"=>"Characterization of mouse monoclonal antibodies against GPCMV.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-10 04:47:16"}

PMC Usage Stats | Further Information

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