Development of a Novel Assay to Assess the Avidity of Dengue Virus-Specific Antibodies Elicited in Response to a Tetravalent Dengue Vaccine

• Published in: The Journal of infectious diseases Vol. 225; no. 9; pp. 1533 - 1544
• Main Authors: Tsuji, Isamu, Dominguez, David, Egan, Michael A, Dean, Hansi J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 04.05.2022
• Subjects: Adolescent; Adult; Affinity; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antigens; Antiviral drugs; Avidity; Child; Clinical trials; Dengue - prevention & control; Dengue fever; Dengue Vaccines; Dengue Virus; Humans; Major and Brief Reports; Monoclonal antibodies; Vaccination; Vaccines; Vaccines, Combined; Virions; Virus-like particles; avidity; vaccine; antibody; virus-like particle; biolayer interferometry; TAK-003; VLP; dengue; BLI
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiab064

Abstract 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. Clinical Trials Registration NCT01511250 and NCT02302066. 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.