Musheng Bao

A CpG oligodeoxynucleotide acts as a potent adjuvant for inactivated rabies virus vaccine.

To develop a CpG containing oligodeoxynucleotide (CpG ODN)-enhanced rabies vaccine for stimulating an earlier production of rabies virus neutralizing antibody (RVNAb) with high titers, we designed a CpG ODN (BW006) and evaluated its adjuvant activities in enhancing the immune response to rabies vaccine with or without aluminum in mice. It was found that BW006 could facilitate the rabies vaccine to induce an earlier and more vigorous RVNAb response, resulting in more effective protection of mice from rabies virus challenge. In addition, three shots of rabies vaccine with BW006 induced compatible RVNAb level with that induced by five shots of aluminum-adjuvanted rabies vaccine. These data reveal that BW006 could be used as a promising adjuvant to replace of or combine with aluminum for developing more effective rabies vaccines.

Anti-SARS-CoV immunity induced by a novel CpG oligodeoxynucleotide.

Abstract To develop CpG oligodeoxynucleotides (CpG ODNs) based therapy for prevention and treatment of severe acute respiratory syndrome (SARS), we selected a novel CpG ODN (BW001), which displays B-type CpG ODN structure feature at the 5′ and A-type CpG ODN structure feature at the 3′, and tested for its anti-SARS-CoV activity. We found that the supernatants of human PBMCs stimulated by BW001 significantly protected Vero cells from SARS-CoV infection. BW001 could stimulate human PBMCs and pDCs to secrete high level of IFN-α and promote human PBMCs and B cells to proliferate. Furthermore, we demonstrated that BW001 could activate CD19+ B cells and CD56+ NK cells in human PBMCs. In addition, BW001 could enhance NK cytotoxicity and IFN-γ secretion in human PBMCs. Together, BW001 represents a novel type of CpG ODN and may have potential for the development of treatment and prevention for SARS as well as other viral associated diseases.

A human microsatellite DNA-mimicking oligodeoxynucleotide with CCT repeats negatively regulates TLR7/9-mediated innate immune responses via selected TLR pathways

Abstract A human microsatellite DNA-mimicking ODN (MS ODN) composed of CCT repeats, designated as SAT05f, has been studied for its capacity of negatively regulating innate immunity induced by TLR7/TLR9 agonists in vitro and in mice. The result showed that SAT05f could down-regulate TLR7/9-dependent IFN-α production in cultured human PBMC stimulated by inactivated Flu virus PR8 or HSV-1 or CpG ODN or imiquimod, protect d-GalN-treated mice from lethal shock induced by TLR9 agonist, not by TLR3/4 agonist. In addition, SAT05f significantly inhibit IFN-α production from purified human plasmacytoid cells (pDCs) stimulated by CpG ODN. Interestingly, SAT05f could up-regulate CD80, CD86, and HLA-DR on the pDCs in vitro, implying that SAT05f-mediated inhibition on IFN-α production could be related to the activation of pDCs. The data suggest that SAT05f could be developed as a candidate medicament for the treatment of TLR7/9 activation-associated diseases by inhibiting TLR7/9 signaling pathways.

A CpG oligodeoxynucleotide inducing anti-coxsackie B3 virus activity in human peripheral blood mononuclear cells

Abstract Coxsackie B3 virus (CVB3) is the most significant pathogen causing myocarditis in humans, and antiviral therapy would be most effective in the early stages of the disease. Here we provide evidence that BW001, a C‐type CpG oligodeoxynucleotide, induces anti‐CVB3 activity in human peripheral blood mononuclear cells (PBMCs). In parallel, we have demonstrated that BW001 induces human PBMCs to express mRNAs of multiple types of interferon (IFN), including IFN‐α, IFN‐β, IFN‐ω and IFN‐γ, and to express mRNAs of at least 11 subtypes of IFN‐α. The induced IFNs may contribute to the anti‐CVB3 activity. The results suggest that BW001 could be developed into a medication with the potential to treat CVB3 infectious diseases by inducing natural mixed IFNs.