TLR3-and MyD88-dependent signaling differentially influences the development of west nile virus-specific B cell responses in mice following immunization with RepliVAX WN, a single-cycle flavivirus vaccine candidate

Jingya Xia, Evandro R. Winkelmann, Summer R. Gorder, Peter W. Mason, Gregg Milligan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Recognition of conserved pathogen-associated molecular patterns (PAMPs) by host pattern recognition receptors (PRRs) results in the activation of innate signaling pathways that drive the innate immune response and ultimately shape the adaptive immune response. RepliVAX WN, a single-cycle flavivirus (SCFV) vaccine candidate derived from West Nile virus (WNV), is intrinsically adjuvanted with multiple PAMPs and induces a vigorous anti-WNV humoral response. However, the innate mechanisms that link pattern recognition and development of vigorous antigen-specific B cell responses are not completely understood. Moreover, the roles of individual PRR signaling pathways in shaping the B cell response to this live attenuated SCFV vaccine have not been established. We examined and compared the role of TLR3-and MyD88-dependent signaling in the development of anti-WNV-specific antibody-secreting cell responses and memory B cell responses induced by RepliVAX WN. We found that MyD88 deficiency significantly diminished B cell responses by impairing B cell activation, development of germinal centers (GC), and the generation of long-lived plasma cells (LLPCs) and memory B cells (MBCs). In contrast, TLR3 deficiency had more effect on maintenance of GCs and development of LLPCs, whereas differentiation of MBCs was unaffected. Our data suggest that both TLR3-and MyD88-dependent signaling are involved in the intrinsic adjuvanting of RepliVAXWNand differentially contribute to the development of vigorous WNV-specific antibody and B cell memory responses following immunization with this novel SCFV vaccine.

Original languageEnglish (US)
Pages (from-to)12090-12101
Number of pages12
JournalJournal of Virology
Volume87
Issue number22
DOIs
StatePublished - 2013

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Flavivirus
West Nile virus
B-lymphocytes
Immunization
immunization
B-Lymphocytes
Vaccines
vaccines
mice
Pattern Recognition Receptors
plasma cells
Plasma Cells
Antibody-Producing Cells
receptors
antibodies
Germinal Center
pathogens
Adaptive Immunity
Innate Immunity
humoral immunity

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Medicine(all)

Cite this

TLR3-and MyD88-dependent signaling differentially influences the development of west nile virus-specific B cell responses in mice following immunization with RepliVAX WN, a single-cycle flavivirus vaccine candidate. / Xia, Jingya; Winkelmann, Evandro R.; Gorder, Summer R.; Mason, Peter W.; Milligan, Gregg.

In: Journal of Virology, Vol. 87, No. 22, 2013, p. 12090-12101.

Research output: Contribution to journalArticle

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