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

Abstract

e West Nile virus (WNV), currently the cause of a serious U.S. epidemic, is a mosquito-borne flavivirus and member of the Japanese encephalitis (JE) serocomplex. There is currently no approved human WNV vaccine, and treatment options remain limited, resulting in significant mortality and morbidity from human infection. Given the availability of approved human JE vaccines, this study asked whether the JE-ADVAX vaccine, which contains an inactivated cell culture JE virus antigen formulated with Advax delta inulin adjuvant, could provide heterologous protection against WNV infection in wild-type and ␤2-microglobulindeficient (␤2m ؊/؊ ) murine models. Mice immunized twice or even once with JE-ADVAX were protected against lethal WNV challenge even when mice had low or absent serum cross-neutralizing WNV titers prior to challenge. Similarly, ␤2m ؊/؊ mice immunized with JE-ADVAX were protected against lethal WNV challenge in the absence of CD8 ؉ T cells and prechallenge WNV antibody titers. Protection against WNV could be adoptively transferred to naive mice by memory B cells from JE-ADVAX-immunized animals. Hence, in addition to increasing serum cross-neutralizing antibody titers, JE-ADVAX induced a memory Bcell population able to provide heterologous protection against WNV challenge. Heterologous protection was reduced when JE vaccine antigen was administered alone without Advax, confirming the importance of the adjuvant to induction of cross-protective immunity. In the absence of an approved human WNV vaccine, JE-ADVAX could provide an alternative approach for control of a major human WNV epidemic.

Vaccinations for Neuroinfectious Disease: A Global Health Priority

“…In this study, WNV protection appeared to be mediated by the induction of cross-protective memory B cells [20]. The JE-ADVAX vaccine is a Vero cell-derived, formalin-inactivated JEV antigen with an Advax adjuvant [20]. Vero cells were originally derived from African green monkey kidney cells and are a widely used platform in vaccine production [21].…”

“…WNV first emerged in the USA in 1999, and over the next ten years there were 12,000 reported cases of West Nile neuroinvasive disease, with a mortality rate of approximately 10 % [20].…”

“…Research has demonstrated that infection with one JE serocomplex virus can provide protection against heterologous viruses, raising the question of harnessing cross-protection for WNV from existing JEV vaccines. In a 2013 study, Petrovsky et al [20] demonstrated that in mice, JE-ADVAX induced complete cross-protection of WNV, with a reduced viral burden and no CNS perivascular lymphocytic infiltrates. In this study, WNV protection appeared to be mediated by the induction of cross-protective memory B cells [20].…”

“…In a 2013 study, Petrovsky et al [20] demonstrated that in mice, JE-ADVAX induced complete cross-protection of WNV, with a reduced viral burden and no CNS perivascular lymphocytic infiltrates. In this study, WNV protection appeared to be mediated by the induction of cross-protective memory B cells [20]. The JE-ADVAX vaccine is a Vero cell-derived, formalin-inactivated JEV antigen with an Advax adjuvant [20].…”

Carbohydrate-Based Adjuvants for Vaccine Production

“…Вместе с тем существование определенных проблем без-опасного применения адъювантов на основе солей алюминия вызывает необходимость разработки новых перспективных адъювантов, отвечающих повышенным требованиям безопас-ности [14,15].…”