Mature B cell deficient-BAFFR^−/− mice can be protected from a lethal WNV-Tx (WNV) infection by vaccination with an anti-CD180 (RP105) antibody - WNVEnv protein conjugate (αCD180-WNVE)

Abstract

BAFFR−/− mice are a model of humoral immunodeficiency since they lack mature B cells. We found that in contrast to WT mice BAFFR^−/− mice were highly susceptible to WNV. BAFFR^−/− mice infected with 100pfu WNV succumbed to infection between 8 to 12 days post-infection and higher virus titers were found in their brains compared to WT mice. Infected BAFFR^−/− mice had substantially reduced WNVE-specific IgG responses and delayed but still detectable WNV neutralizing Ab compared to WT mice. Passive transfer of immune sera from previously infected WT mice rescued BAFFR^−/− mice as well as μMT mice lacking all B cells, but in contrast to μMT mice that all died around 30 days post-infection, BAFFR^−/− mice survived and were able to overcome a second WNV challenge. Furthermore, rescued BAFFR^−/− mice receiving immune sera later produced their own WNVE-specific IgG, although at much lower levels than WT mice. These data suggested that protective immunity could be induced in these mature B cell-deficient mice. Indeed, one injection of αCD180-WNVE 30 days prior to WNV infection induced strong neutralizing Ab responses in BAFFR^−/− mice and significant protective immunity against a normally lethal infection. In contrast, μMT mice could not be protected by αCD180-WNVE immunization confirming that the vaccination requires B cells to induce protective immunity to WNV infection. BAFFR^−/− mice have a profound reduction in mature B cells but, unlike μMT mice, have normal numbers of T1 B cells, which our laboratory has shown previously can make IgG Abs. Interestingly, αCD180 immunization rapidly expands T1/T2 B cells. Thus a CD180-based vaccine may be useful to induce protective immunity in immune compromised individuals. (Supported by NIH grants AI83109 and AI52203).