Neutralizing antibodies targeting a novel epitope on envelope protein exhibited broad protection against flavivirus without risk of disease enhancement.

BACKGROUND: Flavivirus causes many serious public health problems worldwide. However, licensed DENV vaccine has restrictions on its use, and there is currently no approved ZIKV vaccine. Development of a potent and safe flavivirus vaccine is urgently needed. As a previous study revealed the epitope, RCPTQGE, located on the bc loop in the E protein domain II of DENV, in this study, we rationally designed and synthesized a series of peptides based on the sequence of JEV epitope RCPTTGE and DENV/ZIKV epitope RCPTQGE. METHODS: Immune sera were generated by immunization with the peptides which were synthesized by using five copies of RCPTTGE or RCPTQGE and named as JEV-NTE and DV/ZV-NTE. Immunogenicity and neutralizing abilities of JEV-NTE or DV/ZV-NTE-immune sera against flavivirus were evaluated by ELISA and neutralization tests, respectively. Protective efficacy in vivo were determined by passive transfer the immune sera into JEV-infected ICR or DENV- and ZIKV-challenged AG129 mice. In vitro and in vivo ADE assays were used to examine whether JEV-NTE or DV/ZV-NTE-immune sera would induce ADE. RESULTS: Passive immunization with JEV-NTE-immunized sera or DV/ZV-NTE-immunized sera could increase the survival rate or prolong the survival time in JEV-challenged ICR mice and reduce the viremia levels significantly in DENV- or ZIKV-infected AG129 mice. Furthermore, neither JEV -NTE- nor DV/ZV-NTE-immune sera induced antibody-dependent enhancement (ADE) as compared with the control mAb 4G2 both in vitro and in vivo. CONCLUSIONS: We showed for the first time that novel bc loop epitope RCPTQGE located on the amino acids 73 to 79 of DENV/ZIKV E protein could elicit cross-neutralizing antibodies and reduced the viremia level in DENV- and ZIKV-challenged AG129 mice. Our results highlighted that the bc loop epitope could be a promising target for flavivirus vaccine development.

The Bone-Protecting Efficiency of Chinese Medicines Compared With Western Medicines in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Comparative Studies.

Background: Rheumatoid Arthritis (RA) is a systemic autoimmune disease leading to joint destruction. The prevention of bone and cartilage destruction has received increased attention in recent years. Objective: To evaluate the current evidences regarding the bone-protecting efficacy of Chinese medicine or the combination of Chinese medicine and Western medicine for RA. Methods: We comprehensively searched PubMed, Embase, the Cochrane Library (www.thecochranelibrary.com), the China National Knowledge Infrastructure (CNKI), the Database for Chinese Technical Periodicals (VIP), and SinoMed. We then performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing the two therapy methods. Results: Sixteen studies including 1,171 patients were included in the final analysis. The results showed that Chinese medicine could significantly improve the bone mineral density (BMD) (mean difference [MD] = 0.05 /g·cm-2, 95% CI [0.03, 0.08], P < 0.00001), and decrease the serum matrix metalloproteinase 3 (MMP-3) ([SMD] = -2.84, 95% CI [-4.22, -1.47], P < 0.0001). Conclusions: Chinese medicine may provide an efficiently alternative choice for the treatment of RA in terms of the bone-protecting efficiency. Given the inherent limitations of the included studies, future well-designed RCTs are required to confirm and update the findings of this analysis.