BackgroundPresenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation.FindingsWe describe ferritin-based protein nanoparticles that display multiple copies of native-like HIV-1 envelope glycoprotein trimers (BG505 SOSIP.664). Trimer-bearing nanoparticles were significantly more immunogenic than trimers in both mice and rabbits. Furthermore, rabbits immunized with the trimer-bearing nanoparticles induced significantly higher neutralizing antibody responses against most tier 1A viruses, and higher responses (but not significantly), to several tier 1B viruses and the autologous tier 2 virus than when the same trimers were delivered as soluble proteins.ConclusionsThis or other nanoparticle designs may be practical ways to improve the immunogenicity of envelope glycoprotein trimers.

C-type lectin receptors (CLRs) are important pattern recognition receptors involved in recognition and induction of adaptive immunity to pathogens. Certain CLRs play an important role in viral infections as they efficiently interact with viruses. However, it has become clear that deadly viruses subvert the function of CLRs to escape antiviral immunity and promote infection. In particular, viruses target CLRs to suppress or modulate type I interferons that play a central role in the innate and adaptive defense against viruses. In this review, we discuss the function of CLRs in binding to enveloped viruses like HIV-1 and Dengue virus, and how uptake and signaling cascades have decisive effects on the outcome of infection.

Strong innate and adaptive immune responses are paramount in combating viral infections. Dendritic cells (DCs) detect viral infections via cytosolic RIG-I like receptors (RLRs) RIG-I and MDA5 leading to MAVS-induced immunity. The DEAD-box RNA helicase DDX3 senses abortive human immunodeficiency virus 1 (HIV-1) transcripts and induces MAVS-dependent type I interferon (IFN) responses, suggesting that abortive HIV-1 RNA transcripts induce antiviral immunity. Little is known about the induction of antiviral immunity by DDX3-ligand abortive HIV-1 RNA. Here we synthesized a 58 nucleotide-long capped RNA (HIV-1 Cap-RNA 58) that mimics abortive HIV-1 RNA transcripts. HIV-1 Cap-RNA 58 induced potent type I IFN responses in monocytederived DCs, monocytes, macrophages and primary CD1c + DCs. Compared with RLR agonist poly-I:C, HIV-1 Cap-RNA 58 induced comparable levels of type I IFN responses, identifying HIV-1 Cap-RNA 58 as a potent trigger of antiviral immunity. In monocyte-derived DCs, HIV-1 Cap-RNA 58 activated the transcription factors IRF3 and NF-κB. Moreover, HIV-1 Cap-RNA 58 induced DC maturation and the expression of proinflammatory cytokines. HIV-1 Cap-RNA 58-stimulated DCs induced proliferation of CD4 + and CD8 + T cells and differentiated naïve T helper (T H) cells toward a T H 2 phenotype. Importantly, treatment of DCs with HIV-1 Cap-RNA 58 resulted in an efficient antiviral innate immune response that reduced ongoing HIV-1 replication in DCs. Our data strongly suggest that HIV-1 Cap-RNA 58 induces potent innate and adaptive immune responses, making it an interesting addition in vaccine design strategies.