Immunogenicity and Safety of a Tetravalent Recombinant Subunit Dengue Vaccine in Adults Previously Vaccinated with a Live Attenuated Tetravalent Dengue Vaccine: Results of a Phase-I Randomized Clinical Trial

Am J Trop Med Hyg. 2020 Aug;103(2):855-863. doi: 10.4269/ajtmh.20-0042. Epub 2020 May 7.

Abstract

New dengue vaccines are needed to prevent this globally expanding vector-borne disease. The V180 vaccine candidate consists of four recombinant, soluble, dengue virus envelope glycoproteins and has been previously evaluated in two clinical trials for safety and immunogenicity in Flavivirus-naive participants (NCT01477580 and NCT0093642). Here, we report on a randomized, placebo-controlled, double-blind study of the safety and immunogenicity of the V180 vaccine in subjects who have previously received the live attenuated tetravalent vaccine (LATV) developed by the National Institute of Allergy and Infectious Diseases (protocol #V180-002 [CIR-301]). The study was designed to evaluate whether this recombinant subunit vaccine could boost the neutralizing antibody responses induced by dengue LATV. Twenty participants who had previously received one or two doses of dengue LATV were randomized and received a single dose of V180 nonadjuvanted (N = 8), V180 adjuvanted with Alhydrogel™ (aluminum hydroxide gel, Brenntag Biosector, Frederikssund, Denmark) (N = 8), or placebo (N = 4). Immunogenicity was measured using a plaque reduction neutralization test at days 1, 15, 28, and 180 after vaccination. In addition, vaccine safety (solicited and unsolicited adverse events) was assessed using a vaccination report card for 28 days following vaccination, and serious adverse events were captured from the time of informed consent through the final study visit at 6 months after vaccination. The results of the study demonstrate that the V180 vaccine is generally well tolerated and immunogenic in these dengue-seropositive volunteers.

Trial registration: ClinicalTrials.gov NCT00936429 NCT01477580.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Aluminum Hydroxide / therapeutic use
  • Antibodies, Neutralizing / immunology
  • Dengue / prevention & control*
  • Dengue Vaccines / therapeutic use*
  • Dengue Virus / immunology
  • Double-Blind Method
  • Female
  • Humans
  • Immunization, Secondary*
  • Immunogenicity, Vaccine
  • Injection Site Reaction
  • Male
  • Middle Aged
  • Neutralization Tests
  • Vaccines, Attenuated / therapeutic use
  • Vaccines, Subunit / therapeutic use
  • Vaccines, Synthetic / therapeutic use
  • Viral Envelope Proteins / immunology
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Dengue Vaccines
  • Vaccines, Attenuated
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • Aluminum Hydroxide

Associated data

  • ClinicalTrials.gov/NCT00936429
  • ClinicalTrials.gov/NCT01477580