Defining levels of dengue virus serotype-specific neutralizing antibodies induced by a live attenuated tetravalent dengue vaccine (TAK-003)

• Published in: PLoS neglected tropical diseases Vol. 15; no. 3; p. e0009258
• Main Authors: White, Laura J., Young, Ellen F., Stoops, Mark J., Henein, Sandra R., Adams, Elizabeth C., Baric, Ralph S., de Silva, Aravinda M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2021; Public Library of Science (PLoS)
• Subjects: Adult; Amino acids; Animals; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antigens; Attenuation; Biology and Life Sciences; Chlorocebus aethiops; Clinical trials; Dengue; Dengue fever; Dengue Vaccines - immunology; Dengue Virus - immunology; Dengue viruses; Disease control; Epitopes - immunology; Fc receptors; Fetal calf serum; Genetic aspects; Genotype & phenotype; Glutamine; Haplorhini; Human diseases; Humans; Identification and classification; Immunity; Immunological research; Infections; Medicine and Health Sciences; Penicillin; Receptors; Research and Analysis Methods; Serogroup; Serotypes; Serum; Streptomycin; Target cells; Tropical diseases; Vaccination; Vaccines; Vector-borne diseases; Vero Cells; Viral antibodies; Viruses; Thailand
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0009258

The four dengue virus serotypes (DENV1-4) infect several hundred million people each year living in tropical and sub-tropical regions. Clinical development of DENV vaccines is difficult because immunity to a single serotype increases risk of severe disease during a second infection with a new serotype. Leading vaccines are based on tetravalent formulations to induce simultaneous and balanced protective immunity to all 4 serotypes. TAK-003 is a tetravalent live attenuated dengue vaccine candidate developed by Takeda Vaccines Inc, which is currently being evaluated in phase 3 efficacy trials. Here, we use antibody depletion methods and chimeric, epitope transplant DENVs to characterize the specificity of neutralizing antibodies in dengue-naïve adults and non-human primates immunized with TAK-003. Our results demonstrate that TAK-003 induced high levels of DENV2 neutralizing antibodies that recognized unique (type-specific) epitopes on DENV2. In contrast, most vaccinated subjects developed lower levels of DENV1, DENV3 and DENV4 neutralizing antibodies that mainly targeted epitopes that were conserved (cross-reactive) between serotypes. Trial Registration: ClinicalTrials.gov NCT02425098 .