Top Reads

Previous work demonstrated the adjuvant monophosphoryl lipid A (MPL) and synthetic cord factor, trehalose-6,6′-dicorynomycolate (TDCM) induced type 1 IFN and significantly increased Ag-specific IgM and IgG. In this Top Read, Spurrier et al. (p. 148) demonstrated that type 1 IFN signaling is required for T cell–independent type 2 Ag (TI-2) responses, but MPL/TDCM can elicit IFN-independent responses. The pneumococcal vaccine, Pneumovax23, was used to study B cell responses with and without MPL/TDCM. Mice deficient in the type I IFN receptor (IFNAR^−/−) or mice treated with an IFNAR antagonist Ab, produced less vaccine-specific IgG and IgM following vaccination, compared with wild-type mice. IgG and IgM responses to TI-2 Ag were similar in the mice with B cell–specific IFNAR deficiency compared with the IFNAR^−/− mice, suggesting that IFNAR expression on B cells was required for TI-2 Ag responses. The addition of MPL/TDCM to vaccination restored the IgG and IgM responses in IFNAR^−/− mice. Although B-1b cells were most responsive to vaccination, the inclusion of MPL/TDCM significantly increased TI-2 Ab responses in these cells, and to a lesser extent in CD23^- B cells, depending on route of vaccine administration, indicating MPL/TDCM mainly enhanced innate B cells responses. These data reveal the importance of IFN signaling in B cell TI-2 Ag responses and provide evidence of an effective adjuvant that activates IFN-alternative pathways to enhance innate B cell response to vaccination.

CD47–signal regulatory protein (SIRP)α modulates myeloid cell activity and is an attractive target for enhancing antitumor immunity. In this Top Read, Yang et al. (p. 204) developed AL008, an Ab that triggers SIRPα degradation. Furthermore, AL008 promotes myeloid cell activation via Fc binding to FcγR. Compared to another SIRPα Ab, AL008 better induced human macrophage phagocytosis of solid tumor and lymphoma cells via FcγR2A in vitro. In addition, AL008 stimulated dendritic cell–mediated T cell proliferation. In a humanized mouse model, AL008 treatment alone slowed tumor growth and enhanced the effects of anti–PD-L1 therapy. This study identified AL008 as a potential antitumor therapeutic that stimulates both the innate and adaptive immune responses.