Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses

Repeated homologous antigen immunization has been hypothesized to hinder antibody diversification, whereas sequential immunization with heterologous immunogens can educate B cell differentiations towards conserved residues thereby facilitating the generation of cross-reactive immunity. In this study...

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Published inFrontiers in immunology Vol. 11; p. 585133
Main Authors Hou, Jue, Ye, Weijian, Loo, Hooi Linn, Wong, Lan Hiong, Chen, Jianzhu
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 25.09.2020
Subjects
dengue virus
epitope-decreasing
immunoglobulin diversification
Immunology
sequential immunization
vaccine development
vaccine development
epitope-decreasing
immunoglobulin diversification
dengue virus
sequential immunization
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Summary:Repeated homologous antigen immunization has been hypothesized to hinder antibody diversification, whereas sequential immunization with heterologous immunogens can educate B cell differentiations towards conserved residues thereby facilitating the generation of cross-reactive immunity. In this study, we developed a sequential vaccination strategy that utilized epitope-decreasing antigens to reinforce the cross-reactivity of T and B cell immune responses against all four serotypes dengue virus. The epitope-decreasing immunization was implemented by sequentially inoculating mice with antigens of decreasing domain complexity that first immunized with DENV1 live-attenuated virus, following by the Envelope protein (Env), and then Env domain III (EDIII) subunit protein. When compared to mice immunized with DENV1 live-attenuated virus three times, epitope-decreasing immunization induced higher TNF-α CD8 T cell immune response against consensus epitopes. Epitope-decreasing immunization also significantly improved neutralizing antibody response to heterologous serotypes. Moreover, this sequential approach promoted somatic hypermutations in the immunoglobulin gene of antigen-specific memory B cells in comparison to repeated immunization. This proof-of-concept work on epitope-decreasing sequential vaccination sheds light on how successively exposing the immune system to decreasing-epitope antigens can better induce cross-reactive antibodies.
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This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology
Reviewed by: Srijayaprakash Babu Uppada, University of Nebraska Medical Center, United States; Marc Paul Girard, Université Paris Diderot, France
Edited by: Neeltje van Doremalen, Rocky Mountain Laboratories (NIAID), United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2020.585133