title: JE-ADVAX vaccine protection against Japanese encephalitis virus mediated by memory B cells in the absence of CD8(+) T cells and pre-exposure neutralizing antibody.
abstract: JE-ADVAX is a new, delta inulin-adjuvanted, Japanese encephalitis (JE) candidate vaccine with a strong safety profile and potent immunogenicity that confers efficient immune protection not only against JE virus but also against related neurotropic flaviviruses such as West Nile virus. In this study, we investigated the immunological mechanism of protection by JE-ADVAX vaccine using knockout mice deficient in B cells or CD8(+) T cells and poor persistence of neutralizing antibody or by adoptive transfer of immune splenocyte subpopulations. We show that memory B cells induced by JE-ADVAX provide long-lived protection against JE even in the absence of detectable pre-exposure serum neutralizing antibodies and without the requirement of CD8(+) T cells. Upon virus encounter, these vaccine-induced memory B cells were rapidly triggered to produce neutralizing antibodies that then protected immunized mice from morbidity and mortality. The findings suggest that the extent of the B-cell memory compartment might be a better immunological correlate for clinical efficacy of JE vaccines than the currently recommended measure of serum neutralizing antibody. This may explain the paradox where JE protection is observed in some subjects even in the absence of detectable serum neutralizing antibody. Our investigation also established the suitability of a novel flavivirus challenge model (β(2)-microglobulin-knockout mice) for studies of the role of B-cell memory responses in vaccine protection.
authors: Department of Emerging Pathogens and Vaccines, John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors: Maximilian
authors: M
authors: Larena
authors: Natalie A
authors: NA
authors: Prow
authors: Roy A
authors: RA
authors: Hall
authors: Nikolai
authors: N
authors: Petrovsky
authors: Mario
authors: M
authors: Lobigs
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004672:Encephalitis, Japanese / Q000276:immunology / Q000517:prevention & control*; D007444:Inulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines; C576871:delta inulin; D007444:Inulin
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