Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines

Background Molecular adjuvants are a promising method to enhance virus-specific immune responses and protect against HIV-1 infection. Immune activation by ligands for receptors such as CD40 can induce dendritic cell activation and maturation. Here we explore the incorporation of two CD40 mimics, Epstein Barr Virus gene LMP1 or an LMP1-CD40 chimera, into a strain of SIV that was engineered to be limited to a single cycle of infection. Results Full length LMP1 or the chimeric protein LMP1-CD40 was cloned into the nef-locus of single-cycle SIV. Human and Macaque monocyte derived macrophages and DC were infected with these viruses. Infected cells were analyzed for activation surface markers by flow cytometry. Cells were also analyzed for secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12p70 and TNF by cytometric bead array. Conclusions Overall, single-cycle SIV expressing LMP1 and LMP1-CD40 produced a broad and potent T$_H$1-biased immune response in human as well as rhesus macaque macrophages and DC when compared with control virus. Single-cycle SIV-LMP1 also enhanced antigen presentation by lentiviral vector vaccines, suggesting that LMP1-mediated immune activation may enhance lentiviral vector vaccines against HIV-1

TRIF mobilizes unique primary defense against Gram-negative bacteria in intestinal interface

The gastrointestinal tract is the largest mucosal surface in our body. It houses diverse microorganisms that collectively form the commensal microbial community. The security of this community is kept by host-microbial interactions and is violated by foreign pathogens that induce local as well as systemic pathology. In most cases, gastrointestinal infections are caused by Gram-negative enteropathogens, which trigger host immune responses through the TLR4 signaling pathways. Although TRIF is one of the major pathways downstream of TLR4, very little is known about how the TRIF pathway contributes to intestinal defense against pathogenic infection. Recently, we reported a unique role of TRIF signaling in host response to an enterophathogen Yersinia enterocolitica, which consisted of IFN-β induction from regional macrophages followed by activation of NK cells in the mesenteric lymph nodes. In this addendum, we show distinct roles for TRIF-dependent host response in intestinal vs. systemic infection with Gram-negative enterophathogens