Human Vaccines & Immunotherapeutics (Sep 2019)

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

  • Susan B. Manoff,
  • Michele Sausser,
  • Amy Falk Russell,
  • Jason Martin,
  • David Radley,
  • Donna Hyatt,
  • Christine C. Roberts,
  • Jason Lickliter,
  • Janakan Krishnarajah,
  • Andrew Bett,
  • Sheri Dubey,
  • Tyler Finn,
  • Beth-Ann Coller

DOI
https://doi.org/10.1080/21645515.2018.1546523
Journal volume & issue
Vol. 15, no. 9
pp. 2195 – 2204

Abstract

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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.

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