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Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice

Authors :
Connor A. P. Scott
Alberto A. Amarilla
Summa Bibby
Natalee D. Newton
Roy A. Hall
Jody Hobson-Peters
David A. Muller
Keith J. Chappell
Paul R. Young
Naphak Modhiran
Daniel Watterson
Source :
Viruses, Vol 13, Iss 9, p 1843 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

The use of dengue virus (DENV) vaccines has been hindered by the complexities of antibody dependent enhancement (ADE). Current late-stage vaccine candidates utilize attenuated and chimeric DENVs that produce particles of varying maturities. Antibodies that are elicited by preferentially exposed epitopes on immature virions have been linked to increased ADE. We aimed to further understand the humoral immunity promoted by DENV particles of varying maturities in an AG129 mouse model using a chimeric insect specific vaccine candidate, bDENV-2. We immunized mice with mature, partially mature, and immature bDENV-2 and found that immunization with partially mature bDENV-2 produced more robust and cross-neutralizing immune responses than immunization with immature or mature bDENV-2. Upon challenge with mouse adapted DENV-2 (D220), we observed 80% protection for mature bDENV-2 vaccinated mice and 100% for immature and partially mature vaccinated mice, suggesting that protection to homotypic challenge is not dependent on maturation. Finally, we found reduced in vitro ADE at subneutralising serum concentrations for mice immunized with mature bDENV-2. These results suggest that both immature and mature DENV particles play a role in homotypic protection; however, the increased risk of in vitro ADE from immature particles indicates potential safety benefits from mature DENV-based vaccines.

Details

Language :
English
ISSN :
19994915
Volume :
13
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
edsdoj.3f3606dab2fa4ab5b55e85340982d4f5
Document Type :
article
Full Text :
https://doi.org/10.3390/v13091843