Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells.

Published online

Journal Article

How previous immunity influences immune memory recall and protection against related flaviviruses is largely unknown, yet encounter with multiple flaviviruses in a lifetime is increasingly likely. Using sequential challenges with dengue virus (DENV), yellow fever virus (YFV), and Japanese encephalitis virus (JEV), we induced cross-reactive cellular and humoral immunity among flaviviruses from differing serocomplexes. Antibodies against JEV enhanced DENV replication; however, JEV immunity was protective in vivo during secondary DENV1 infection, promoting rapid gains in antibody avidity. Mechanistically, JEV immunity activated dendritic cells and effector memory T cells, which developed a T follicular helper cell phenotype in draining lymph nodes upon secondary DENV1 infection. We identified cross-reactive epitopes that promote recall from a pool of flavivirus serocomplex cross-reactive memory CD4 T cells and confirmed that a similar serocomplex cross-reactive immunity occurs in humans. These results show that sequential immunizations for flaviviruses sharing CD4 epitopes should promote protection during a subsequent heterologous infection.

Full Text

Duke Authors

Cited Authors

  • Saron, WAA; Rathore, APS; Ting, L; Ooi, EE; Low, J; Abraham, SN; St John, AL

Published Date

  • July 2018

Published In

Volume / Issue

  • 4 / 7

Start / End Page

  • eaar4297 -

PubMed ID

  • 29978039

Pubmed Central ID

  • 29978039

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.aar4297

Language

  • eng

Conference Location

  • United States