Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 225, Issue 9, Pages 1533-1544Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab064
Keywords
dengue; TAK-003; vaccine; BLI; biolayer interferometry; avidity; antibody; virus-like particle; VLP
Categories
Funding
- Takeda Vaccines, Inc.
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A novel avidity assay using biolayer interferometry and dengue virus-like particles was developed to assess antibody affinity maturation. Vaccination with tetravalent dengue vaccine candidate (TAK-003) increased avidity index, which remained high throughout 1 year postvaccination.
Antibody affinity maturation is a critical step in development of functional antiviral immunity; however, accurate measurement of affinity maturation of polyclonal serum antibody responses to particulate antigens such as virions is challenging. We describe a novel avidity assay employing biolayer interferometry and dengue virus-like particles. After validation using anti-dengue monoclonal antibodies, the assay was used to assess avidity of antibody responses to a tetravalent dengue vaccine candidate (TAK-003) in children, adolescents, and adults during two phase 2 clinical trials conducted in dengue-endemic regions. Vaccination increased avidity index and avidity remained high through 1 year postvaccination. Neutralizing antibody titers and avidity index did not correlate overall; however, a correlation was observed between neutralizing antibody titer and avidity index in those subjects with the highest degree of antibody affinity maturation. Therefore, vaccination with TAK-003 stimulates polyclonal affinity maturation and functional antibody responses, including neutralizing antibodies. To assess antibody affinity maturation, a novel dengue virus avidity assay was developed employing biolayer interferometry and dengue virus-like particles. Vaccination with tetravalent dengue vaccine candidate (TAK-003) increased avidity index, which remained high throughout 1 year.
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