Specificity and Breadth of the Neutralizing Antibody Response to a Live-Attenuated Tetravalent Dengue Vaccine
Christina R. DeMaso, Lovkesh Karwal, Melissa Zahralban-Steele, David Ernesto Marón Domínguez, Zhang-Li Springer, Maima Kaiser, Sunil Palani, Tim Rindfleisch, Kelly Bohning, Greg Hather, Subash C. Das, Mayuri Sharma, Hansi Dean
Abstract
BACKGROUND: An effective dengue vaccine should ideally induce broadly neutralizing antibody (nAb) responses against all 4 dengue virus (DENV) serotypes. METHODS: We characterized the specificity and breadth of the nAb response to TAK-003, a live-attenuated tetravalent dengue vaccine, in serum samples from phase 2 and 3 clinical trials. RESULTS: Microneutralization tests using postvaccination serum showed comparable neutralization against diverse DENV-1-4 genotypes. Reporter virus particle neutralization assays after depletion of anti-DENV-2 nAbs demonstrated that the nAb response to DENV-1, -3, and -4 comprises both type-specific (TS) and cross-reactive (CR) nAbs. CONCLUSIONS: Therefore, TAK-003 induces broad tetravalent TS and CR nAb responses.