Immunogenicity and safety of an investigational tetravalent recombinant subunit vaccine for dengue: results of a Phase I randomized clinical trial in flavivirus-naïve adults

• Main Authors: Susan B. Manoff (Author), Michele Sausser (Author), Amy Falk Russell (Author), Jason Martin (Author), David Radley (Author), Donna Hyatt (Author), Christine C. Roberts (Author), Jason Lickliter (Author), Janakan Krishnarajah (Author), Andrew Bett (Author), Sheri Dubey (Author), Tyler Finn (Author), Beth-Ann Coller (Author)
• Format: Book
• Published: Taylor & Francis Group, 2019-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2164-5515; 2164-554X; 10.1080/21645515.2018.1546523
• Keywords: dengue vaccine; recombinant; subunit; immunogenicity; safety; Immunologic diseases. Allergy; RC581-607; Therapeutics. Pharmacology; RM1-950
• Source: Human Vaccines & Immunotherapeutics, Vol 15, Iss 9, Pp 2195-2204 (2019)

There is an unmet medical need for vaccines to prevent dengue. V180 is an investigational recombinant subunit vaccine that consists of truncated dengue envelope proteins (DEN-80E) for all 4 serotypes. Three dosage levels of the tetravalent DEN-80E antigens were assessed in a randomized, placebo-controlled, Phase I dose-escalation, first-in-human proof-of-principle trial in healthy, flavivirus-naïve adults in Australia (NCT01477580). The 9 V180 formulations that were assessed included either ISCOMATRIX™ adjuvant (2 dosage levels), aluminum-hydroxide adjuvant, or were unadjuvanted, and were compared to phosphate-buffered saline placebo. Volunteers received 3 injections of assigned product on a 0, 1, 2 month schedule, and were followed for safety through 1 year after the last injection. Antibody levels were assessed at 6 time-points: enrollment, 28 days after each injection, and 6 and 12 months Postdose 3 (PD3). Of the 98 randomized participants, 90 (92%) received all 3 injections; 83 (85%) completed 1-year follow-up. Immunogenicity was measured by a qualified Focus Reduction Neutralization Test with a 50% neutralization cutoff (FRNT50). All 6 V180 formulations with ISCOMATRIX™ adjuvant showed robust immunogenicity, while the 1 aluminum-adjuvanted and 2 unadjuvanted formulations were poorly immunogenic. Geometric mean antibody titers generally declined at 6 months and 1 year PD3. All 9 V180 formulations were generally well tolerated. Formulations with ISCOMATRIX™ adjuvant were associated with more adverse events than aluminum-adjuvanted or unadjuvanted formulations.