Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination

Jennifer E Munt; Sandra Henein; Cameron Adams; Ellen Young; Yixuan J Hou; Helen Conrad; Deanna Zhu; Stephanie Dong; Nurgun Kose; Boyd Yount; Rita M Meganck; Long Ping V Tse; Guillermina Kuan; Angel Balmaseda; Michael J Ricciardi; David I Watkins; James E Crowe Jr; Eva Harris; Aravinda M DeSilva; Ralph S Baric

doi:10.1016/j.chom.2023.10.004

Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination

Cell Host Microbe. 2023 Nov 8;31(11):1850-1865.e5. doi: 10.1016/j.chom.2023.10.004. Epub 2023 Oct 30.

Authors

Jennifer E Munt¹, Sandra Henein², Cameron Adams², Ellen Young¹, Yixuan J Hou¹, Helen Conrad¹, Deanna Zhu¹, Stephanie Dong¹, Nurgun Kose³, Boyd Yount¹, Rita M Meganck¹, Long Ping V Tse¹, Guillermina Kuan⁴, Angel Balmaseda⁵, Michael J Ricciardi⁶, David I Watkins⁷, James E Crowe Jr³, Eva Harris⁸, Aravinda M DeSilva², Ralph S Baric⁹

Affiliations

¹ Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
² Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.
³ Vanderbilt Vaccine Center, Nashville, TN, USA.
⁴ Health Center Socrates Flores Vivas, Ministry of Health, Managua, Nicaragua; Sustainable Sciences Institute, Managua, Nicaragua.
⁵ Sustainable Sciences Institute, Managua, Nicaragua; National Virology Laboratory, National Center for Diagnosis and Reference, Ministry of Health, Managua, Nicaragua.
⁶ George Washington University, Washington, DC, USA.
⁷ University of Massachusetts Medical School, Worcester, MA, USA.
⁸ Division of Infectious Diseases and Vaccinology, School of Public Health, University of California Berkeley, Berkeley, CA, USA.
⁹ Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: rbaric@email.unc.edu.

PMID: 37909048
DOI: 10.1016/j.chom.2023.10.004

Abstract

The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or III. However, the relative contribution of these domain-specific antibodies is unclear. To identify the primary DENV3 nAb targets in sera after natural infection or vaccination, chimeric DENV1 recombinant encoding DENV3 EDI, EDII, or EDIII were generated. DENV3 EDII is the principal target of TS polyclonal nAb responses and encodes two or more neutralizing epitopes. In contrast, some were individuals vaccinated with a DENV3 monovalent vaccine-elicited serum TS nAbs targeting each ED in a subject-dependent fashion, with an emphasis on EDI and EDIII. Vaccine responses were also sensitive to DENV3 genotypic variation. This DENV1/3 panel allows the measurement of serum ED TS nAbs, revealing differences in TS nAb immunity after natural infection or vaccination.

Keywords: RNA; antibody; dengue virus; immunity; monoclonal; natural infection; polyclonal; sera; structural targets; vaccine.

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
Dengue Vaccines*
Dengue Virus*
Dengue*
Glycoproteins
Humans
Vaccination
Viral Envelope Proteins / genetics

Substances

Antibodies, Viral
Antibodies, Neutralizing
Dengue Vaccines
Viral Envelope Proteins
Glycoproteins