{"doi":"10.1101/2022.06.02.494515","title":"Control of SIV infection in prophylactically vaccinated, ART-naïve macaques is required for the most efficacious CD8 T cell response during treatment with the IL-15 superagonist N-803","abstract":"Abstract The IL-15 superagonist N-803 has been shown to enhance the function of CD8 T cells and NK cells. We previously found that in a subset of vaccinated, ART-naïve, SIV+ rhesus macaques, N-803 treatment led to a rapid but transient decline in plasma viremia that positively correlated with an increase in the frequency of CD8 T cells. Here we tested the hypothesis that prophylactic vaccination was required for N-803 mediated suppression of SIV plasma viremia. We vaccinated rhesus macaques with a DNA prime/Ad5 boost regimen using vectors expressing SIVmac239 gag, with or without a plasmid expressing IL-12, or left them unvaccinated. Animals were then intravenously infected with SIVmac239M. Six months after infection, animals were treated with N-803. We found no differences in control of plasma viremia during N-803 treatment between vaccinated and unvaccinated macaques. Furthermore, the SIV-specific CD8 T cells displayed no differences in frequency or ability to traffic to the lymph nodes. Interestingly, when we divided the SIV+ animals based on plasma viral load set-point prior to N-803 treatment, N-803 increased the frequency of SIV-specific T cells expressing ki-67+ and granzyme B+ in animals with low plasma viremia (<10 4 copies/mL; SIV controllers) compared to animals with high plasma viremia (>10 4 copies/mL;SIV non-controllers). In addition, Gag-specific CD8 T cells from the SIV+ controllers had a greater increase in CD107a+CD8+ T cells when compared to SIV+ non-controllers. Overall, our results indicate that N-803 is most effective in SIV+ animals with a pre-existing immunological ability to control SIV replication.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303495,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473624,"name":"Alexis J. Balgeman","orcid":"0000-0003-2627-7975","position":1,"is_corresponding":false},{"id":560501,"name":"Olivia E. Harwood","orcid":"0000-0002-0315-9645","position":2,"is_corresponding":false},{"id":372354,"name":"Ryan V. Moriarty","orcid":"0000-0001-7100-1906","position":3,"is_corresponding":false},{"id":247223,"name":"Jeffrey T. Safrit","orcid":"0000-0001-7441-4423","position":4,"is_corresponding":false},{"id":332158,"name":"Andrea M. Weiler","orcid":"0000-0002-7130-8235","position":5,"is_corresponding":false},{"id":332162,"name":"Thomas C. Friedrich","orcid":"0000-0001-9831-6895","position":6,"is_corresponding":false},{"id":333888,"name":"Shelby L. O’Connor","orcid":"0000-0003-0183-5010","position":7,"is_corresponding":false},{"id":473623,"name":"Amy Ellis","orcid":"0000-0002-6503-1399","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:24.307938Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}