PMID- 29617814 OWN - NLM STAT- MEDLINE DCOM- 20190912 LR - 20240328 IS - 1537-6613 (Electronic) IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 218 IP - 3 DP - 2018 Jul 2 TI - A Respiratory Syncytial Virus Vaccine Based on the Small Hydrophobic Protein Ectodomain Presented With a Novel Lipid-Based Formulation Is Highly Immunogenic and Safe in Adults: A First-in-Humans Study. PG - 378-387 LID - 10.1093/infdis/jiy177 [doi] AB - BACKGROUND: Respiratory syncytial virus infection can cause lower respiratory tract infection in older adults comparable to influenza, but no vaccines are available. METHODS: This was a randomized, observer-blinded, first-in-humans study of a novel synthetic RSV antigen based on the ectodomain of the small hydrophobic glycoprotein (SHe) of RSV subgroup A, formulated with either the lipid and oil-based vaccine platform DepoVax (DPX-RSV[A]) or alum (RSV[A]-Alum), in healthy, 50-64-year-old individuals. Two dose levels (10 or 25 microg) of SHe with each formulation were compared to placebo. A booster dose was administered on day 56. RESULTS: There was no indication that the vaccine was unsafe. Mild pain, drowsiness, and muscles aches were the most common solicited adverse events (AEs), and the frequencies of the AEs did not increase after dose 2. Robust anti-SHe-specific immune responses were demonstrated in the DPX-RSV(A) 10-mug and 25-mug groups (geometric mean titer, approximately 10-fold and 100-fold greater than that of placebo at days 56 and 236, respectively), and responses were sustained in the DPX-RSV(A) 25-mug group at day 421. Responses to the RSV(A)-Alum vaccines were very low. CONCLUSIONS: A novel antigen from the SH protein of RSV, formulated in a lipid and oil-based vaccine platform, was highly immunogenic, with sustained antigen-specific antibody responses, and had an acceptable safety profile. FAU - Langley, Joanne M AU - Langley JM AD - Canadian Center for Vaccinology (Dalhousie University, IWK Health Centre, and the Nova Scotia Health Authority). AD - Department of Pediatrics, Dalhousie University, Halifax, Canada. AD - Department of Community Health and Epidemiology, Dalhousie University, Halifax, Canada. FAU - MacDonald, Lisa D AU - MacDonald LD AD - Immunovaccine, Halifax, Canada. FAU - Weir, Genevieve M AU - Weir GM AD - Immunovaccine, Halifax, Canada. FAU - MacKinnon-Cameron, Donna AU - MacKinnon-Cameron D AD - Canadian Center for Vaccinology (Dalhousie University, IWK Health Centre, and the Nova Scotia Health Authority). FAU - Ye, Lingyun AU - Ye L AD - Canadian Center for Vaccinology (Dalhousie University, IWK Health Centre, and the Nova Scotia Health Authority). FAU - McNeil, Shelly AU - McNeil S AD - Canadian Center for Vaccinology (Dalhousie University, IWK Health Centre, and the Nova Scotia Health Authority). AD - Department of Pediatrics, Dalhousie University, Halifax, Canada. AD - Department of Community Health and Epidemiology, Dalhousie University, Halifax, Canada. AD - Department of Medicine, Dalhousie University, Halifax, Canada. FAU - Schepens, Bert AU - Schepens B AD - VIB-UGent Center for Medical Biotechnology, VIB, Ghent University, Ghent, Belgium. AD - Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium. FAU - Saelens, Xavier AU - Saelens X AD - VIB-UGent Center for Medical Biotechnology, VIB, Ghent University, Ghent, Belgium. AD - Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium. FAU - Stanford, Marianne M AU - Stanford MM AD - Canadian Center for Vaccinology (Dalhousie University, IWK Health Centre, and the Nova Scotia Health Authority). AD - Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada. AD - Immunovaccine, Halifax, Canada. FAU - Halperin, Scott A AU - Halperin SA AD - Canadian Center for Vaccinology (Dalhousie University, IWK Health Centre, and the Nova Scotia Health Authority). AD - Department of Pediatrics, Dalhousie University, Halifax, Canada. AD - Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada. LA - eng GR - CIHR/Canada PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Adjuvants, Immunologic) RN - 0 (Alum Compounds) RN - 0 (Antibodies, Viral) RN - 0 (Lipids) RN - 0 (Placebos) RN - 0 (Respiratory Syncytial Virus Vaccines) RN - 0 (Retroviridae Proteins, Oncogenic) RN - 0 (Vaccines, Subunit) RN - 0 (small hydrophobic protein, virus) RN - 34S289N54E (aluminum sulfate) SB - IM MH - Adjuvants, Immunologic/*administration & dosage MH - Alum Compounds/administration & dosage MH - Antibodies, Viral/*blood MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology MH - Female MH - Healthy Volunteers MH - Humans MH - Immunity, Humoral MH - Immunization Schedule MH - Lipids/*administration & dosage MH - Male MH - Middle Aged MH - Placebos/administration & dosage MH - Respiratory Syncytial Virus Infections/*prevention & control MH - Respiratory Syncytial Virus Vaccines/administration & dosage/adverse effects/*immunology MH - Respiratory Syncytial Virus, Human/*immunology MH - Retroviridae Proteins, Oncogenic/*immunology MH - Single-Blind Method MH - Vaccines, Subunit/administration & dosage/adverse effects/immunology PMC - PMC6049039 EDAT- 2018/04/05 06:00 MHDA- 2019/09/13 06:00 PMCR- 2018/03/30 CRDT- 2018/04/05 06:00 PHST- 2017/12/14 00:00 [received] PHST- 2018/03/28 00:00 [accepted] PHST- 2018/04/05 06:00 [pubmed] PHST- 2019/09/13 06:00 [medline] PHST- 2018/04/05 06:00 [entrez] PHST- 2018/03/30 00:00 [pmc-release] AID - 4956800 [pii] AID - jiy177 [pii] AID - 10.1093/infdis/jiy177 [doi] PST - ppublish SO - J Infect Dis. 2018 Jul 2;218(3):378-387. doi: 10.1093/infdis/jiy177.