Role of B cell memory immunity in secondary heterotypic dengue virus infection in mice (67.2)

Abstract

Abstract While severe dengue disease has been associated with heterotypic secondary (2°) DENV infection, most 2° infections result in asymptomatic or mild disease. The role of the memory B cell response in mediating cross-protection against a 2° heterotypic infection is not well understood. DENV infection of AG129 (interferon-a/b and -g receptor-deficient) mice reproduces features of human disease. Prior infection with DENV1 protects mice against a lethal 2° infection with DENV2 strain D2S10. DENV1-immune mice treated with cyclophosphamide (CP) and infected with D2S10 died on day 7.5-8.5, demonstrating a role for the cellular immune response in protection. In contrast, naïve CP-treated mice experiencing a 1° infection with D2S10, died on day 4, suggesting that pre-formed Ab play a role in protection. Adoptive transfer of immune memory B cells into naïve mice prior to 2° infection delayed mortality but was not sufficient to protect against a lethal infection. Mice depleted of T cells developed sign of disease but recovered after 2° infection. We are further investigating the respective role of B cells by treating mice with anti-CD20 and by comparing the avidity of post-1°, pre-2° infection serum (LPC response) with that of the supernatant obtained after polyclonal B cell stimulation (B cell memory response). Understanding the role of immune memory in protection will be useful for dengue vaccine development and evaluation.