Safety and Immunogenicity of a Shigella flexneri 2a Invaplex 50 Intranasal Vaccine in Adult Volunteers

摘要

Shigellosis is a leading cause of diarrhea worldwide prompting vaccine development The Shigella flexneri lnvaplex 50 is a macromolecular complex containing lpaB, lpaC, and LPS, formulated from an aqueous extract of virulent Shigella delivered via nasal administration. Preclinical vaccine testing demonstrated safety, immunogenicity and efficacy. An open-label dose- escalating phase 1 study evaluated a 3-dose (2-week intervals) regimen via nasal pipette delivery. Thirty-two subjects were enrolled into one of four vaccine dose groups ( 10, 50, 240, or 480 micrograms). The vaccine was well tolerated with minor short-lived nasal symptoms without evidence of dose effect. Antibody-secreting cell (ASC) responses were elicited at doses >equal 50 micrograms with the highest lgG ASC, Invaplex 50 (100%) and S.flexneri 2a LPS (71%), as well as. serologic responses (43%) occurring with the 240 micrograms dose. FecallgA responses, Invaplex 50 (38.5%) and LPS (30.8%) were observed at doses >=240 micrograms. The lnvaplex 50 nasal vaccine was safe with encouraging mucosal immune responses. Follow-on studies will optimize dose, delivery mechanism and assess efficacy in aS. flexneri 2a challenge study.