Protective effect of a RSV subunit vaccine candidate G1F/M2 was enhanced by a HSP70-Like protein in mice

Respiratory syncytial virus (RSV) is a major respiratory pathogen in newborns. Neonate vaccine should induce strong protective immunity. We have engineered a subunit vaccine candidate G1F/M2. A major problem in developing subunit vaccines is their limited immunogenicity. Aluminium adjuvants with a long history of use with routine childhood vaccines have some limitations, especially inability to elicit CTL response. There is a need for alternative adjuvants. Heat shock proteins (HSPs) are characterized as potent immunoadjuvants. In this study, HSP70-like protein 1 (HSP70L1) gene was cloned. The recombinant protein HSP70L1 was expressed in E. coli, purified and renaturated. We evaluated the potential of HSP70L1 used as the adjuvant of G1F/M2. G1F/M2 was chemically cross-linked with HSP70L1 (HSP-G1F/M2). HSP70L1 enhanced significantly the immunogenicity and protective effect of G1F/M2. HSP-G1F/M2 induced significant higher levels of antibodies, neutralizing antibodies and CTL activity than unadjuvanted G1F/M2. The antibody titers induced by HSP-G1F/M2 were similar to that by G1F/M2 + Alum. RSV-specific CTL activity induced by HSP-G1F/M2 was stronger than that by G1F/M2 + Alum. Interestingly, the protective effect of HSP-G1F/M2 against RSV was significantly stronger than that of G1F/M2 + Alum. The results suggest that HSP70L1 is a potent adjuvant of G1F/M2.     

Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice

Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract worldwide. There is currently no clinically approved vaccine against RSV infection. Recently, it has been shown that a replication-deficient first generation adenoviral vector (FGAd), which encodes modified RSV attachment glycoprotein (G), elicits long-term protective immunity against RSV infection in mice. The major problem in developing such a vaccine is that G protein lacks MHC-I-restricted epitopes. However, RSV fusion glycoprotein (F) is a major cytotoxic T-lymphocyte epitope in humans and mice, therefore, an FGAd-encoding F (FGAd-F) was constructed and evaluated for its potential as an RSV vaccine in a murine model. Intranasal (i.n.) immunization with FGAd-F generated serum IgG, bronchoalveolar lavage secretory IgA, and RSV-specific CD8+ T-cell responses in BALB/c mice, with characteristic balanced or mixed Th1/Th2 CD4+ T-cell responses. Serum IgG was significantly elevated after boosting with i.n. FGAd-F. Upon challenge, i.n. immunization with FGAd-F displayed an effective protective role against RSV infection. These results demonstrate FGAd-F is able to induce effective protective immunity and is a promising vaccine regimen against RSV infection.     

Effect of Cheonggukjang supplementation upon hepatic acyl-CoA synthase, carnitine palmitoyltransferase I, acyl-CoA oxidase and uncoupling protein 2 mRNA levels in C57BL/6J mice fed with high fat diet

This study investigated the effect of Cheonggukjang on mRNA levels of hepatic acyl-CoA synthase (ACS), carnitine palmitoyltransferase I (CPT-I), acyl-CoA oxidase (ACO) and uncoupling protein 2 (UCP2), and on serum lipid profiles in C57BL/6J mice. Thirty male C57BL/6J mice were divided into three groups; normal diet (ND), high fat diet (HD) and high fat diet with 40% Cheonggukjang (HDC). Energy intake was significantly higher in the HDC group than in the ND and HD groups. The HDC group normalized in weight gain, epididymal and back fat (g/100 g) accumulation which are increased by high fat diet. Serum concentrations of triglyceride and total cholesterol in the HDC were significantly lower than those in the HD group. These results were confirmed by hepatic mRNA expression of enzymes and protein (ACS, CPT-1, ACO, UCP2) which is related with lipid metabolism by RT-PCR. Hepatic CPT-I, ACO and UCP2 mRNA expression was increased by Cheonggukjang supplementation. We demonstrated that Cheonggukjang supplement leads to increased mRNA expressions of enzymes and protein involved in fatty acid oxidation in liver, reduced accumulation of body fat and improvement of serum lipids in high fat diet fed mice.