Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees
Summary: 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 perfor...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720312158 |
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| author | David R. Martinez Boyd Yount Usha Nivarthi Jennifer E. Munt Matthew J. Delacruz Stephen S. Whitehead Anna P. Durbin Aravinda M. de Silva Ralph S. Baric |
| author_facet | David R. Martinez Boyd Yount Usha Nivarthi Jennifer E. Munt Matthew J. Delacruz Stephen S. Whitehead Anna P. Durbin Aravinda M. de Silva Ralph S. Baric |
| author_sort | David R. Martinez |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-12T21:27:46Z |
| format | Article |
| id | doaj.art-f08922d8a3db45c9993b10a150269f7f |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T21:27:46Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f08922d8a3db45c9993b10a150269f7f2022-12-22T00:11:25ZengElsevierCell Reports2211-12472020-10-01331108226Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in VaccineesDavid R. Martinez0Boyd Yount1Usha Nivarthi2Jennifer E. Munt3Matthew J. Delacruz4Stephen S. Whitehead5Anna P. Durbin6Aravinda M. de Silva7Ralph S. Baric8Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Corresponding authorDepartment of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Microbiology and Immunology, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USADepartment of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Microbiology and Immunology, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USALaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USAJohns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USADepartment of Microbiology and Immunology, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USADepartment of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720312158dengue virus 2prM and E protein genetic variationgenotypeantibodyneutralizationvaccines |
| spellingShingle | David R. Martinez Boyd Yount Usha Nivarthi Jennifer E. Munt Matthew J. Delacruz Stephen S. Whitehead Anna P. Durbin Aravinda M. de Silva Ralph S. Baric Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees Cell Reports dengue virus 2 prM and E protein genetic variation genotype antibody neutralization vaccines |
| title | Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees |
| title_full | Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees |
| title_fullStr | Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees |
| title_full_unstemmed | Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees |
| title_short | Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees |
| title_sort | antigenic variation of the dengue virus 2 genotypes impacts the neutralization activity of human antibodies in vaccinees |
| topic | dengue virus 2 prM and E protein genetic variation genotype antibody neutralization vaccines |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720312158 |
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