Immunogenicity and efficacy of flagellin-envelope fusion dengue vaccines in mice and monkeys

Clinical and Vaccine Immunology : CVI
Ge LiuLynda Tussey

Abstract

The envelope (E) protein of flaviviruses includes three domains, EI, EII, and EIII, and is the major protective antigen. Because EIII is rich in type-specific and subcomplex-specific neutralizing epitopes and is easy to express, it is particularly attractive as a recombinant vaccine antigen. VaxInnate has developed a vaccine platform that genetically links vaccine antigens to bacterial flagellin, a Toll-like receptor 5 ligand. Here we report that tetravalent dengue vaccines (TDVs) consisting of four constructs, each containing two copies of EIII fused to flagellin (R3.2x format), elicited robust and long-lived neutralizing antibodies (geometric mean titers of 200 to 3,000), as measured with a 50% focus reduction neutralization test (FRNT50). In an immunogenicity study, rhesus macaques (n = 2) immunized subcutaneously with 10 μg or 90 μg of TDV three or four times, at 4- to 6-week intervals, developed neutralizing antibodies to four dengue virus (DENV) serotypes (mean post-dose 3 FRNT50 titers of 102 to 601). In an efficacy study, rhesus macaques (n = 4) were immunized intramuscularly with 16 μg or 48 μg of TDV or a placebo control three times, at 1-month intervals. The animals that received 48-μg doses of TDV developed neutrali...Continue Reading

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Citations

Oct 2, 2015·Vaccine·Kirsten S VanniceJoachim Hombach
Sep 8, 2018·Frontiers in Immunology·Nagesh K Tripathi, Ambuj Shrivastava
Jan 19, 2019·PeerJ·Yao LeiYongguang Zhang
Apr 2, 2020·Applied Microbiology and Biotechnology·Abhishek Singh RathoreRinkoo Devi Gupta
Mar 11, 2020·Frontiers in Immunology·Kyle SaylorChenming Zhang
Apr 9, 2020·Acta Biomaterialia·Prateek BhardwajRinti Banerjee
Aug 26, 2021·Scientific Reports·Sathishkumar Arumugam, Prasad Varamballi

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