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

An Inactivated Cell Culture Japanese Encephalitis Vaccine (JE-ADVAX) Formulated with Delta Inulin Adjuvant Provides Robust Heterologous Protection against West Nile Encephalitis via Cross-Protective Memory B Cells and Neutralizing Antibody

“…We have recently shown that the memory B-cell response elicited by immunization with JE-ADVAX provided durable homologous protection against JEV in the absence of both detectable preexposure serum neutralizing antibody and CD8 ϩ T cells (27). This protective function of memory B cells was demonstrated in mice lacking intact ␤2-microglobulin (␤2m Ϫ/Ϫ mice).…”

“…These mice display a deficiency in CD8 ϩ T cells (38) as well as markedly reduced serum IgG levels (39-41) as a result of the impaired ability, in the absence of ␤2m, of neonatal Fc receptor recycling of IgG (42). An additional advantage of the use of ␤2m Ϫ/Ϫ mice for studies of the immunological mechanism of WNV protection is their high susceptibility to viral challenge (27). Consistent with the previously observed high susceptibility to JEV infection, high mortality was seen in naive ␤2m Ϫ/Ϫ mice infected with a small s.c. dose (10 3 PFU) of virulent WNV, with all animals succumbing to lethal encephalitis by day 13 postinfection (Fig.…”

“…JEV protection (27) and suggests that memory B cells can play a role at least equal to that of cross-reactive serum neutralizing antibody in offering protection against homologous and heterologous flaviviruses. Indeed, when challenge occurs in the absence of preformed cross-reactive serum neutralizing antibody, such as in ␤2m Ϫ/Ϫ mice, memory B cells almost certainly assume a dominant role in cross-protection.…”

“…In preclinical models, Advax was shown to enhance the immunogenicity of a broad range of viral vaccines, including pandemic influenza virus (23), HIV (24), hepatitis B virus (25), African horse sickness virus (26), and JEV (18,27). JE-ADVAX is a recently developed JEV vaccine based on the combination of Advax adjuvant with a Vero cellderived, formalin-inactivated JEV antigen (28).…”

Carbohydrate-Based Adjuvants for Vaccine Production

“…При применении у мышей, крыс, морских свинок, кроликов, цыплят, собак, овец, обезьян, лошадей и верблюдов данный адъювант усиливал иммуногенность различных бел-ковых антигенов, выделенных из вирусных, бактериальных и протозойных патогенных микроорганизмов, токсинов, опу-холевых антигенов и аллергенов. Адъювант Advax™ усиливал иммуногенность вакцин, что было показано на моделях мы-шей, инфицированных вирусами гриппа H1N1 [21], японского энцефалита [22], лихорадки Западного Нила [14], гепатита В [23] и вирусом иммунодефицита человека [24]. Адъювантное действие Advax™ продемонстрировано также на моделях хорь-ков, зараженных вирусом гриппа птиц H5N1 [25], лошадей, инфицированных японским энцефалитом [26], и верблюдов, зараженных вирусом африканской конской чумы и сапа [27].…”