Development and Pre-Clinical Evaluation of Two LAIV Strains against Potentially Pandemic H2N2 Influenza Virus
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{"title"=>"Development and pre-clinical evaluation of two LAIV strains against potentially pandemic H2N2 influenza virus", "type"=>"journal", "authors"=>[{"first_name"=>"Irina", "last_name"=>"Isakova-Sivak", "scopus_author_id"=>"23973026600"}, {"first_name"=>"Jørgen", "last_name"=>"De Jonge", "scopus_author_id"=>"16237869900"}, {"first_name"=>"Tatiana", "last_name"=>"Smolonogina", "scopus_author_id"=>"26536628100"}, {"first_name"=>"Andrey", "last_name"=>"Rekstin", "scopus_author_id"=>"6603364748"}, {"first_name"=>"Geert", "last_name"=>"Van Amerongen", "scopus_author_id"=>"7004695265"}, {"first_name"=>"Harry", "last_name"=>"Van Dijken", "scopus_author_id"=>"6602168951"}, {"first_name"=>"Justin", "last_name"=>"Mouthaan", "scopus_author_id"=>"55908085500"}, {"first_name"=>"Paul", "last_name"=>"Roholl", "scopus_author_id"=>"7005256517"}, {"first_name"=>"Victoria", "last_name"=>"Kuznetsova", "scopus_author_id"=>"57000245400"}, {"first_name"=>"Elena", "last_name"=>"Doroshenko", "scopus_author_id"=>"55584015500"}, {"first_name"=>"Vadim", "last_name"=>"Tsvetnitsky", "scopus_author_id"=>"6602357791"}, {"first_name"=>"Larisa", "last_name"=>"Rudenko", "scopus_author_id"=>"7005033248"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84904802066", "pui"=>"373618210", "isbn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0102339", "issn"=>"19326203", "scopus"=>"2-s2.0-84904802066", "pmid"=>"25058039"}, "id"=>"6907d1de-77c7-3745-8dbd-2b1882306cdc", "abstract"=>"H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, H2N2 is regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemagglutinins of the two different H2N2 lineages that circulated at the end of the cycle, using the well characterized A/Leningrad/134/17/57 (H2N2) master donor virus as the backbone. The vaccine strains containing the HA and NA of A/California/1/66 (clade 1) or A/Tokyo/3/67 (clade 2) showed a temperature sensitive and cold adapted phenotype and a reduced reproduction that was limited to the respiratory tract of mice, suggesting that the vaccines may be safe for use in humans. Both vaccine strains induced haemagglutination inhibition titers in mice. Vaccination abolished virus replication in the nose and lung and protected mice from weight loss after homologous and heterologous challenge with the respective donor wild type strains. In ferrets, the live attenuated vaccines induced high virus neutralizing, haemagglutination and neuraminidase inhibition titers, however; the vaccine based on the A/California/1/66 wt virus induced higher homologous and better cross-reactive antibody responses than the A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus reduction observed in the throat and nose of ferrets vaccinated with this vaccine after challenge with either of the wild type donor viruses. Moreover, both vaccines clearly reduced the infection-induced rhinitis observed in placebo-vaccinated ferrets. The results favor the vaccine based on the A/California/1/66 isolate, which will be evaluated in a clinical study.", "link"=>"http://www.mendeley.com/research/development-preclinical-evaluation-two-laiv-strains-against-potentially-pandemic-h2n2-influenza-viru", "reader_count"=>13, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>2, "Student > Master"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>2, "Student > Master"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>4, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1607538"], "description"=>"<p>Antibody responses in ferrets against early (1957) and late (1968) Neuraminidase 14 (hatched boxes) and 21 (open boxes) days after vaccination. Titers induced by the 17/Cal/395 (blue), 17/Tok/326 (green) and Len/17 (red) vaccines are grouped by the respective antigens indicated at the top of the panels. The X31 strain that contains the HA and NA genes of A/Honk Kong/1/1968 (H3N2) was used as a representative for the late NA genes, whereas the reassortant A/17/duck/Potsdam/86/92 (H5N2), which contains the N2 of A/Leningrad/134/1957 (H2N2) was used as a representative of the early NA genes. NI-titers were defined at 50% inhibition of the total neuraminidase activity of a standardized amount of the viruses. In sera of placebo-vaccinated animals and in sera taken prior to vaccination, background titers were detected, but were considered aspecific effects of the serum (not shown). Presented are box plots of log<sub>2</sub> transformed NI-titers. Bars indicate the 5–95 percentile and black dots indicate the average titer. Significant lower titers with respect to the 17/Cal/395 induced NI-titers are indicated by *. Significant lower titers with respect to the 17/Tok/326 induced NI-titers are indicated by an <sup>$</sup> and significant lower titers with respect to the Len/17 induced NI-titers are indicated by an <sup>#</sup>. One symbol refers to p<0.05 and two symbols refer to p<0.0001.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "inhibition", "antibody", "titers"], "article_id"=>1116512, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g006", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neuraminidase_Inhibition_antibody_titers_in_ferrets_/1116512", "title"=>"Neuraminidase Inhibition antibody titers in ferrets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607551"], "description"=>"<p>List of universal primers, which were used for partial sequencing of genes of H2N2 reassortant influenza viruses.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "sequencing", "genes", "h2n2", "reassortant", "influenza"], "article_id"=>1116525, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.t001", "stats"=>{"downloads"=>6, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_List_of_universal_primers_which_were_used_for_partial_sequencing_of_genes_of_H2N2_reassortant_influenza_viruses_/1116525", "title"=>"List of universal primers, which were used for partial sequencing of genes of H2N2 reassortant influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607533"], "description"=>"<p>Homologous and cross-reactive antibody responses in mice 21 days after 1<sup>st</sup> vaccination (hatched boxes) and 21 days after 2<sup>nd</sup> vaccination (day 42; open boxes) as measured by haemagglutination inhibition. Titers induced by the 17/Cal/395 (blue) and 17/Tok/326 (green) vaccines (either at a dose of 100 MID<sub>50</sub> or 1000 MID<sub>50</sub>) are grouped by the respective antigens indicated at the top of the panels. Serum was titrated against 4HAU of the respective wild type viruses using 0.5% chicken erythrocytes. In sera of placebo vaccinated animals and sera prior to vaccination no titers above detection limit were detected (not shown). Presented are box plots of log<sub>2</sub> transformed HI-titers. Bars indicate the 5–95 percentile and black dots indicate the average titer.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "cross-reactivity", "h2n2", "laiv", "candidates"], "article_id"=>1116507, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g002", "stats"=>{"downloads"=>2, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunogenicity_and_cross_reactivity_of_H2N2_LAIV_candidates_in_a_mouse_model_/1116507", "title"=>"Immunogenicity and cross-reactivity of H2N2 LAIV candidates in a mouse model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607550"], "description"=>"<p>Antigenic characterization of H2N2 viruses.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "characterization", "h2n2"], "article_id"=>1116524, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.t003", "stats"=>{"downloads"=>7, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antigenic_characterization_of_H2N2_viruses_/1116524", "title"=>"Antigenic characterization of H2N2 viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607547"], "description"=>"<p>NA activity was assessed in the fetuin cleavage assay. The analysis was performed at virus concentration of 8–512 agglutination units in triplicate and the average activity of strains tested was expressed as a percentage of positive control (RDE). Dashed lines indicate the 95% confidence band of fitting curve (continuous line).</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "percent", "rde", "h2n2", "laiv"], "article_id"=>1116521, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g010", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NA_activity_in_percent_of_RDE_activity_for_H2N2_LAIV_candidates_/1116521", "title"=>"NA activity in percent of RDE activity for H2N2 LAIV candidates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607532"], "description"=>"<p>Groups of 6 female CBA mice were infected i.n. with the corresponding viruses at a dose of 100 MID<sub>50</sub> in a volume of 50 µl. Three days after inoculation, mice were euthanized and lungs and nasal turbinateswere harvested. Virus titers in the organs were determined by end-point titration in eggs and expressed as log<sub>10</sub>EID<sub>50</sub>/ml. Significant lower titers with respect to the donor viruses are indicated by * (p<0,05) or ** (p<0,005). Bars indicate the average titer.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "h2n2", "influenza", "respiratory", "organs"], "article_id"=>1116506, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g001", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_of_H2N2_influenza_viruses_in_respiratory_organs_and_brain_of_mice_/1116506", "title"=>"Replication of H2N2 influenza viruses in respiratory organs and brain of mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607545"], "description"=>"<p>Representative protection against damage induced by H2N2 wt infection in the nasal turbinates 5 days after challenge (shown here: A/Cal/1/66). Represented are a negative control ferret that was not vaccinated and challenged with a placebo (Panel A), a placebo-vaccinated animal challenged with wt virus (panel B) and an LAIV (in this case 17/Tok/326) vaccinated animal challenged with wt virus (panel C). Shown are 5 µm sections stained with haematoxylin and eosin with bars indicating 50 µm. Stars indicate moderate exudate of polymorphic nuclear cells in the lumen (panel B) or absence of exudate (panel A and C). Arrows indicate flattening or absence of the epithelial lining (panel B) or normal epithelial lining (panel A and C). Open stars indicate presence of inflammation in the submucosa (panel B) or absence/reduced inflammation and normal epithelium (panel A and C). The infection-induced pathology was scored on a scale of 1–5 based on the parameters described in the materials and methods in which a score of 0 refers to no aberration and a score of 5 refers to severe aberrations. In panel D, the overall infection pathology (end score) after challenge with either A/Tokyo/3/67 (triangles) or A/California/1/66 (circles) is presented. *indicates a significant difference (p≤0.05).</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models"], "article_id"=>1116519, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g009", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathological_representation_and_analysis_of_infection_damage_/1116519", "title"=>"Histopathological representation and analysis of infection damage.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607541"], "description"=>"<p>Virus titers in the nose (nasal turbinates) 5 days after challenge with either A/Tokyo/3/67 (triangles) or A/California/1/66 (circles). The virus titers in the homogenized samples were determined by end-point titration on MDCK cells using a 5 fold serial dilution. Presented are the individual log<sub>10</sub> transformed titers and the average is presented by a bar. * indicates a significant difference (p≤0.05)and dotted line indicates limit of detection.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "titers"], "article_id"=>1116515, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g008", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virus_titers_in_the_nose_/1116515", "title"=>"Virus titers in the nose.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607535"], "description"=>"<p>Animals were vaccinated twice with 17/Cal/395 (blue) using a low dose (diamonds) or a high dose (inverted triangles) or with 17/Tok/326 (green) using a low dose (triangles) or a high dose (squares). Placebo animals are indicated by circles. The animals were challenged 21 days after second vaccination with 100 MID<sub>50</sub> of either A/California/1/66 (lower panel) or A/Tokyo/3/67 (upper panel) wild-type virus on day 42 after the first immunization. Five mice in each group were weighed and monitored daily until 14 days after challenge.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "mice", "challenged", "h2n2", "wild-type"], "article_id"=>1116509, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentage_weight_loss_of_mice_challenged_with_H2N2_wild_type_viruses_/1116509", "title"=>"Percentage weight loss of mice challenged with H2N2 wild-type viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607549"], "description"=>"<p>n/t, not tested.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "temperatures", "eggs", "median", "h2n2", "laiv", "candidates"], "article_id"=>1116523, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.t002", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reproductive_capacity_at_different_temperatures_in_eggs_and_median_mouse_infection_dose_MID_50_of_H2N2_LAIV_candidates_and_their_parental_viruses_/1116523", "title"=>"Reproductive capacity at different temperatures in eggs and median mouse infection dose (MID<sub>50</sub>) of H2N2 LAIV candidates and their parental viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607534"], "description"=>"<p>The animals were challenged with 100 MID<sub>50</sub> of either A/California/1/66 (left panel) or A/Tokyo/3/67 (right panel) wild-type virus on day 42 after the first immunization. Three days after challenge, respiratory (lung and nasal turbinates) and systemic (spleen and brain – not shown) organs were collected from four mice in each group. Virus titers in the organs were determined by end-point titration in eggs and expressed as log<sub>10</sub>EID<sub>50</sub>/ml. The depicted vaccine groups represent the low (100MID<sub>50</sub>) and high (1000MID<sub>50</sub>) dose as these were all below detection limit.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "h2n2", "organs", "immunized"], "article_id"=>1116508, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g003", "stats"=>{"downloads"=>4, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_of_H2N2_challenge_viruses_in_organs_of_immunized_mice_/1116508", "title"=>"Replication of H2N2 challenge viruses in organs of immunized mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607548"], "description"=>"1<p>The Area Under Curve was deduced from the area under curve (after challenge) above the baseline (38.0 ± 0.7 °C) temperature (before challenge);</p>2<p>The maximum temperature increase represents the highest recorded increase in temperature above the baseline during any of the measurements after challenge;</p>3<p>Number of the temperature loggers used for the calculations. Initially all ferrets we implanted with a transponder, but after recovery the measurements of some of the transponders could not be retrieved, due to battery or recording failure;</p><p>*indicates significant difference compared to placebo group (p<0.05).</p><p>The body temperature was recorded at intervals of 30 minutes by an intraperitoneally implanted temperature transponder.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "days", "ferrets", "immunized", "h2n2", "laiv"], "article_id"=>1116522, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.t004", "stats"=>{"downloads"=>4, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_the_body_temperature_during_five_days_after_challenge_of_ferrets_immunized_with_H2N2_LAIV_strains_/1116522", "title"=>"Analysis of the body temperature during five days after challenge of ferrets immunized with H2N2 LAIV strains.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607539"], "description"=>"<p>Ferrets vaccinated with either placebo (squares), 17/Cal/395 (triangles), 17/Tok/326 (inverted triangles) or Len/17 (diamonds) were challenged 21 days after vaccination with either A/Tok/67 wt (upper panel) or A/Cal/66 wt (lower panel) virus. Throat swabs were taken prior to the challenge and 2, 3 and 5 days after challenge. The virus titer (TCID<sub>50</sub>) in the transport buffer was determined by end-point titration on MDCK cells using a 5 fold serial dilution. Presented are the average log<sub>10</sub> transformed titers. Bars represent the standard deviation and the dotted line indicates limit of detection.</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "titers", "swabs", "ferrets", "challenged", "wt", "h2n2"], "article_id"=>1116513, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g007", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virus_titers_in_the_throat_swabs_of_ferrets_challenged_with_wt_H2N2_viruses_/1116513", "title"=>"Virus titers in the throat swabs of ferrets challenged with wt H2N2 viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607537"], "description"=>"<p>Homologous and cross-reactive antibody responses in ferrets 14 (hatched boxes) and 21 (open boxes) days after vaccination represented by HI-titers (upper panel) and VN<sub>50</sub> titers (lower panel). Titers induced by the 17/Cal/395 (blue), 17/Tok/326 (green) and Len/17 (red) vaccines are grouped by the respective antigens indicated at the top of the panels. Titers were measured against the vaccine strain as a representative of haemagglutinin of the wild type viruses (HI-titer determination) and against the wild-type strains (VN<sub>50</sub> determination). Serum was titrated against 4HAU of the respective virus using 0.5% turkey erythrocytes (HI-titer determination) and against 100 TCID<sub>50</sub> of the respective wild type virus (VN<sub>50</sub> determination). In sera of placebo-vaccinated animals and sera prior to vaccination, no titers above detection limit were detected (not shown). Presented are box plots of log<sub>2</sub> transformed HI-titers and log<sub>10</sub> transformed 50% Virus Neutralization titers. Bars indicate the 5–95 percentile and black dots indicate the average titer. Significant lower titers with respect to the homologous titers are indicated by * (p<0,05) or ** (p<0,0001) and significant lower titers compared with the other heterologous strain are indicated by <sup>#</sup> (p<0,05) or <sup>##</sup> (p<0,0001).</p>", "links"=>[], "tags"=>["immunology", "Immune system", "Acquired immune system", "immunity", "Humoral immunity", "Vaccination and immunization", "microbiology", "Virology", "Viral transmission and infection", "Viral clearance", "Viral load", "Emerging viral diseases", "Viral classification", "Viral vaccines", "Animal models of infection", "organisms", "viruses", "RNA viruses", "Pathology and laboratory medicine", "pathogenesis", "Model organisms", "Animal models", "Mouse models", "inhibition", "neutralization", "titers"], "article_id"=>1116511, "categories"=>["Biological Sciences"], "users"=>["Irina Isakova-Sivak", "Jørgen de Jonge", "Tatiana Smolonogina", "Andrey Rekstin", "Geert van Amerongen", "Harry van Dijken", "Justin Mouthaan", "Paul Roholl", "Victoria Kuznetsova", "Elena Doroshenko", "Vadim Tsvetnitsky", "Larisa Rudenko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102339.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Haemagglutination_Inhibition_and_Virus_Neutralization_titers_in_ferrets_/1116511", "title"=>"Haemagglutination Inhibition and Virus Neutralization titers in ferrets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:54:27"}

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