{"id":"doi:10.1038/s41467-024-54289-9","kind":"article","title":"A self-amplifying RNA RSV prefusion-F vaccine elicits potent immunity in pre-exposed and naïve non-human primates","authors":["Vijayan A","Vogels R","Groppo R","Jin Y","Khan S","Van Kampen M","Jorritsma S","Boedhoe S","Baert M","van Diepen H","Kuipers H","Serroyen J","Del Valle JR","Broman A","Nguyen L","Ray S","Jarai B","Arora J","Lifton M","Mildenberg B","Morton G","Santra S","Grossman TR","Schuitemaker H","Custers J"],"author_count":26,"year":2024,"published":"2024-11-14","venue":"Nature communications","cited_by":15,"doi":"10.1038/s41467-024-54289-9","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-024-54289-9","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-024-54289-9","updated":null,"pmid":"39543172","pmcid":"PMC11564874","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC11564874/pdf","abstract":"Newly approved subunit and mRNA vaccines for respiratory syncytial virus (RSV) demonstrate effectiveness in preventing severe disease, with protection exceeding 80% primarily through the generation of antibodies. An alternative vaccine platform called self-amplifying RNA (saRNA) holds promise in eliciting humoral and cellular immune responses. We evaluate the immunogenicity of a lipid nanoparticle (LNP)-formulated saRNA vaccine called SMARRT.RSV.preF, encoding a stabilized form of the RSV fusion protein, in female mice and in non-human primates (NHPs) that are either RSV-naïve or previously infected. Intramuscular vaccination with SMARRT.RSV.preF vaccine induces RSV neutralizing antibodies and cellular responses in naïve mice and NHPs. Importantly, a single dose of the vaccine in RSV pre-exposed NHPs elicits a dose-dependent anamnestic humoral immune response comparable to a subunit RSV preF vaccine. Notably, SMARRT.RSV.preF immunization significantly increases polyfunctional RSV.F specific memory CD4 + and CD8 + T-cells compared to RSV.preF protein vaccine. Twenty-four hours post immunization with SMARRT.RSV.preF, there is a dose-dependent increase in the systemic levels of inflammatory and chemotactic cytokines associated with the type I interferon response in NHPs, which is not observed with the protein vaccine. We identify a cluster of analytes including IL-15, TNFα, CCL4, and CXCL10, whose levels are significantly correlated with each other after SMARRT.RSV.preF immunization. These findings suggest saRNA vaccines have the potential to be developed as a prophylactic RSV vaccine based on innate, cellular, and humoral immune profiles they elicit.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"A self-amplifying RNA RSV prefusion-F vaccine elicits potent immunity in pre-exposed and naïve non-human primates\" by Vijayan A, Vogels R, Groppo R et al., https://doi.org/10.1038/s41467-024-54289-9, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}