Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees

• Published in: Cell reports (Cambridge) 2020-10, Vol.33 (1), p.108226-108226, Article 108226
• Main Authors: Martinez, David R., Yount, Boyd, Nivarthi, Usha, Munt, Jennifer E., Delacruz, Matthew J., Whitehead, Stephen S., Durbin, Anna P., de Silva, Aravinda M., Baric, Ralph S.
• Format: Article
• Language: English
• Subjects: Antibodies, Neutralizing - metabolism; antibody; Antigenic Variation; Dengue Virus - genetics; dengue virus 2; Genotype; Humans; neutralization; prM and E protein genetic variation; Vaccination - methods; vaccines
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108226

Dengue virus (DENV) infects an estimated 390 million people each year worldwide. As tetravalent DENV vaccines have variable efficacy against DENV serotype 2 (DENV2), we evaluated the role of genetic diversity within the pre-membrane (prM) and envelope (E) proteins of DENV2 on vaccine performance. We generated a recombinant DENV2 genotype variant panel with contemporary prM and E isolates that are representative of global genetic diversity. The DENV2 genotype variants differ in growth kinetics, morphology, and virion stability. Importantly, the DENV2 genotypic variants are differentially neutralized by monoclonal antibodies, polyclonal serum neutralizing antibodies from DENV2-infected human subjects, and vaccine-elicited antibody responses from the TV003 NIH DENV2 monovalent and DENV tetravalent vaccines. We conclude that DENV2 prM and E genetic diversity significantly modulates antibody neutralization activity. These findings have important implications for dengue vaccines, which are being developed under the assumption that intraserotype variation has minimal impact on neutralizing antibodies. [Display omitted] •Dengue virus serotype 2 (DENV2) genotypic variants have distinct characteristics•DENV2 genotypic variants exhibit variation in proteins prM and E•DENV2 prM and E variation modulates the neutralization activity of human mAbs•DENV2 genotypes are differentially neutralization-susceptible to vaccine antibodies Martinez et al. demonstrate that dengue virus serotype 2 (DENV2) genetic variation modulates neutralizing antibody activity from infection and vaccination. This observation underlines that genotypic variation impacts dengue virus 2 evasion from humoral immunity, suggesting that intraserotype genotypic variation should be considered in designing dengue vaccines.