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{"title"=>"A Single Vaccination with an Improved Nonspreading Rift Valley Fever Virus Vaccine Provides Sterile Immunity in Lambs", "type"=>"journal", "authors"=>[{"first_name"=>"Nadia", "last_name"=>"Oreshkova", "scopus_author_id"=>"52663966100"}, {"first_name"=>"Lucien", "last_name"=>"van Keulen", "scopus_author_id"=>"6701619847"}, {"first_name"=>"Jet", "last_name"=>"Kant", "scopus_author_id"=>"55171043500"}, {"first_name"=>"Rob J.M.", "last_name"=>"Moormann", "scopus_author_id"=>"7006536560"}, {"first_name"=>"Jeroen", "last_name"=>"Kortekaas", "scopus_author_id"=>"35280439500"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84886043555", "pui"=>"370089728", "doi"=>"10.1371/journal.pone.0077461", "sgr"=>"84886043555", "pmid"=>"24167574"}, "id"=>"39a1d7a8-9126-30bd-934d-7a7f77b4d978", "abstract"=>"Rift Valley fever virus (RVFV) is an important pathogen that affects ruminants and humans. Recently we developed a vaccine based on nonspreading RVFV (NSR) and showed that a single vaccination with this vaccine protects lambs from viremia and clinical signs. However, low levels of viral RNA were detected in the blood of vaccinated lambs shortly after challenge infection. These low levels of virus, when present in a pregnant ewe, could potentially infect the highly susceptible fetus. We therefore aimed to further improve the efficacy of the NSR vaccine. Here we report the expression of Gn, the major immunogenic protein of the virus, from the NSR genome. The resulting NSR-Gn vaccine was shown to elicit superior CD8 and CD4-restricted memory responses and improved virus neutralization titers in mice. A dose titration study in lambs revealed that the highest vaccination dose of 10(6.3) TCID50/ml protected all lambs from clinical signs and viremia. The lambs developed neutralizing antibodies within three weeks after vaccination and no anamnestic responses were observed following challenge. The combined results suggest that sterile immunity was achieved by a single vaccination with the NSR-Gn vaccine.", "link"=>"http://www.mendeley.com/research/single-vaccination-improved-nonspreading-rift-valley-fever-virus-vaccine-provides-sterile-immunity-l", "reader_count"=>19, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>3, "Other"=>2, "Student > Master"=>4, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>3, "Other"=>2, "Student > Master"=>4, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>4, "Veterinary Science and Veterinary Medicine"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>2}}, "group_count"=>0}

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• http://doi.org/10.1016/j.vaccine.2014.07.037
• http://doi.org/10.1016/j.molimm.2015.02.001
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• http://doi.org/10.1371/journal.pntd.0008942
• http://doi.org/10.1186/s13567-018-0516-z
• http://doi.org/10.1002/biot.201800238
• http://doi.org/10.3390/v11030237
• http://doi.org/10.1128/JVI.00961-14
• http://doi.org/10.1371/journal.pone.0142670
• http://doi.org/10.1099/vir.0.067660-0
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• http://doi.org/10.1089/vbz.2014.1650

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1254916"], "description"=>"<p>(A) Schematic representation of the S segment of RVFV (upper panel) and the S segment in which the NSs gene is replaced for the codon-optimized Gn gene (lower panel). Distribution of Gn in Rep-Gn cells (B and E) and in BHK cells infected with NSR-Gn at an MOI of 0.5 (C and F). Panels D and G represent BHK control cells. Upper panels represent permeabilized cells and lower panels represent nonpermeabilized cells. The cells were stained with an anti-Gn monoclonal antibody and a Texas Red-labeled secondary antibody. Nuclei were visualized by DAPI staining.</p>", "links"=>[], "tags"=>["s-gn"], "article_id"=>830081, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Lucien van Keulen", "Jet Kant", "Rob J. M. Moormann", "Jeroen Kortekaas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0077461.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Construction_of_the_S_Gn_segment_and_expression_of_Gn_/830081", "title"=>"Construction of the S-Gn segment and expression of Gn.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-22 03:12:34"}
• {"files"=>["https://ndownloader.figshare.com/files/1254917"], "description"=>"<p>(A) VNT titers in sera collected from mice vaccinated with NSR or NSR-Gn before vaccination (DPV -1) and 13, 22 and 29 DPV. Bars represent average titers (n = 6) of each group with standard deviation. The detection limit of the assay is depicted by the interrupted line. (B) Detection of IFN-γ-producing splenocytes isolated from mice vaccinated with NSR or NSR-Gn. Splenocytes were isolated and seeded at a density of 5×10⁵ cells/well in triplicate and stimulated for 12 hours with the indicated peptides or the ectodomain of Gn. Bars represent an average number of IFN-γ producing cells (n = 4) per group with standard deviation. The non-parametric Mann-Whitney test was used for statistical analysis and statistical significance between the groups is depicted by asterisks (*p<0.05; **p<0.01).</p>", "links"=>[], "tags"=>["cellular", "responses", "elicited", "vaccination", "mice", "nsr"], "article_id"=>830082, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Lucien van Keulen", "Jet Kant", "Rob J. M. Moormann", "Jeroen Kortekaas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0077461.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Humoral_and_cellular_immune_responses_elicited_by_vaccination_of_mice_with_NSR_or_NSR_Gn_/830082", "title"=>"Humoral and cellular immune responses elicited by vaccination of mice with NSR or NSR-Gn.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-22 03:12:34"}
• {"files"=>["https://ndownloader.figshare.com/files/1254918"], "description"=>"<p>Fever was defined as a rectal body temperature above 40.5°C (interrupted line). Body temperatures of mock-vaccinated lambs (C1–C8) and lambs vaccinated with a low dose (L1–L8), medium dose (M1–M8) or high dose (H1–H7) of NSR-Gn are depicted individually.</p>", "links"=>[], "tags"=>["temperatures", "vaccinated", "mock-vaccinated", "lambs"], "article_id"=>830083, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Lucien van Keulen", "Jet Kant", "Rob J. M. Moormann", "Jeroen Kortekaas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0077461.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rectal_temperatures_of_vaccinated_and_mock_vaccinated_lambs_before_and_after_challenge_with_RVFV_/830083", "title"=>"Rectal temperatures of vaccinated and mock-vaccinated lambs before and after challenge with RVFV.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-22 03:12:34"}
• {"files"=>["https://ndownloader.figshare.com/files/1254919"], "description"=>"<p>Plasma samples were collected daily at the first 7 days post challenge (DPC) and subsequently on DPC 9, 11, 14 and 21. Viral RNA copy numbers detected in individual animals of the mock-vaccinated group (C1–C8), low-dose group (L1–L8), medium-dose group (M1–M8) and high-dose group (H1–H7) are depicted.</p>", "links"=>[], "tags"=>["viral", "rna", "plasma"], "article_id"=>830084, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Lucien van Keulen", "Jet Kant", "Rob J. M. Moormann", "Jeroen Kortekaas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0077461.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_viral_RNA_in_plasma_by_qRT_PCR_/830084", "title"=>"Detection of viral RNA in plasma by qRT-PCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-22 03:12:34"}
• {"files"=>["https://ndownloader.figshare.com/files/1254920"], "description"=>"<p>Sera were obtained from lambs of the mock group, low-dose group, medium-dose group and high-dose group. The white bars represent VNT titers determined 21 days post vaccination (DPV) and the black bars represent the VNT titers determined 21 days post challenge (DPC). Results obtained from analysis of each individual animal from the mock-group (C1–C8), low-dose group (L1–L8), medium-dose group (M1–M8) and high-dose group (H1–H7) are depicted. The detection limit of the assay is represented by an interrupted line. Lamb C3 died 7 days after challenge, therefore no serum sample was collected at 21 DPC.</p>", "links"=>[], "tags"=>["neutralization"], "article_id"=>830085, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Lucien van Keulen", "Jet Kant", "Rob J. M. Moormann", "Jeroen Kortekaas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0077461.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virus_neutralization_test_VNT_/830085", "title"=>"Virus neutralization test (VNT).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-22 03:12:34"}
• {"files"=>["https://ndownloader.figshare.com/files/1254921"], "description"=>"<p>Sera were obtained 7, 14 and 21 days post vaccination (DPV) and at 0, 7, 14 and 21 days post challenge (DPC). Titers are expressed as percentage competition ratio of the optical densities (OD) of the sample and the OD of the negative control (%S/N). All values lower than 40% are considered positive, between 40–50% are considered doubtful and above 50% are considered negative. The 40% and 50% cut-offs are represented by solid and interrupted lines, respectively. Results obtained from analysis of each individual animal from the mock-group (C1–C8), low-dose group (L1–L8), medium-dose group (M1–M8) or high-dose group (H1–H7) are depicted.</p>", "links"=>[], "tags"=>["anti-n", "antibodies"], "article_id"=>830086, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Lucien van Keulen", "Jet Kant", "Rob J. M. Moormann", "Jeroen Kortekaas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0077461.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_anti_N_antibodies_by_ELISA_/830086", "title"=>"Detection of anti-N antibodies by ELISA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-22 03:12:34"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime