{"doi":"10.17615/qb4q-dk73","title":"Enhanced Control of Pathogenic Simian Immunodeficiency Virus SIVmac239 Replication in Macaques Immunized with an Interleukin-12 Plasmid and a DNA Prime-Viral Vector Boost Vaccine Regimen","abstract":"DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent “blips” in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication.","journal":"UNC Libraries","year":2020,"id":112199,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.946,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":532553,"name":"A. Schultz","orcid":null,"position":1,"is_corresponding":false},{"id":532554,"name":"G. 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King","orcid":null,"position":13,"is_corresponding":false},{"id":150754,"name":"J. W. Coleman","orcid":null,"position":14,"is_corresponding":false},{"id":532566,"name":"C.-D. Wu","orcid":null,"position":15,"is_corresponding":false},{"id":532567,"name":"B. K. Felber","orcid":null,"position":16,"is_corresponding":false},{"id":532568,"name":"Karla F Mullen","orcid":null,"position":17,"is_corresponding":false},{"id":532569,"name":"T. J. Zamb","orcid":null,"position":18,"is_corresponding":false},{"id":437137,"name":"M. G. Hudgens","orcid":null,"position":19,"is_corresponding":false},{"id":532570,"name":"H. Cassamasa","orcid":null,"position":20,"is_corresponding":false},{"id":532571,"name":"G. N. Pavlakis","orcid":null,"position":21,"is_corresponding":false},{"id":532572,"name":"I. Ouellette","orcid":null,"position":22,"is_corresponding":false},{"id":532573,"name":"F. Lin","orcid":null,"position":23,"is_corresponding":false},{"id":218075,"name":"Adrian B. 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