Respiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possible to reduce the hospitalization rate for high-risk children by anti-RSV antibody prophylaxis. RSV has been shown to modify the immune response to infection, a feature linked in part to RSV G protein CX3C chemokine mimicry. This study determined if vaccination with G protein polypeptides or peptides spanning the central conserved region of the G protein could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and disease pathogenesis mediated by RSV infection. The results show that mice vaccinated with G protein peptides or polypeptides containing the CX3C motif generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis, reduce lung virus titers, and prevent body weight loss and pulmonary inflammation. The results suggest that RSV vaccines that induce antibodies that block G protein CX3C-CX3CR1 interaction may offer a new, safe, and efficacious RSV vaccine strategy.

Traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the reduction and control of infectious disease outbreaks. However, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. Recent discoveries that led to increased understanding of viral molecular biology and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agents. Due to their ability to effectively induce both humoral and cell-mediated immune responses, viral vectors are deemed as an attractive alternative to the traditional platforms to deliver vaccine antigens as well as to specifically target and kill tumor cells. With potential targets ranging from cancers to a vast number of infectious diseases, the benefits resulting from successful application of viral vectors to prevent and treat human diseases can be immense.

Respiratory syncytial virus (RSV) is a primary cause of severe lower respiratory tract disease in infants, young children, and the elderly worldwide, and despite decades of effort, there remains no safe and effective vaccine. RSV modifies the host immune response during infection by CX3C chemokine mimicry adversely affecting pulmonary leukocyte chemotaxis and CX3CR1+ RSV-specific T-cell responses. In this study we investigated whether immunization of mice with RSV G protein polypeptides from strain A2 could induce antibodies that block G protein-CX3CR1 interactions of both RSV A and B strains. The results show that mice immunized with RSV A2 G polypeptides generate antibodies that block binding of RSV A2 and B1 native G proteins to CX3CR1, and that these antibodies effectively cross-neutralize both A and B strains of RSV. These findings suggest that vaccines that induce RSV G protein-CX3CR1 blocking antibodies may provide a disease intervention strategy in the efforts to develop safe and efficacious RSV vaccines.

Nanoparticle vaccines were produced using layer-by-layer fabrication and incorporating respiratory syncytial virus (RSV) G protein polypeptides comprising the CX3C chemokine motif. BALB/c mice immunized with G protein nanoparticle vaccines produced a neutralizing antibody response that inhibited RSV replication in the lungs following RSV challenge. ELISPOT analysis showed that G nanoparticle vaccinated mice had increased levels of RSV G protein-specific IL-4 and IFN-γ secreting cells compared to controls following RSV challenge. Remarkably, RSV challenge of G protein nanoparticle vaccinated mice resulted in increased RSV M2-specific IL-4 and IFN-γ secreting T cells, and increased M2-specific H-2Kd-tetramer positive CD8+ T cells in the lungs compared to controls. Cell type analysis showed vaccination was not associated with increased pulmonary eosinophilia following RSV challenge. These results demonstrate that vaccination of mice with the RSV G protein nanoparticle vaccines induces a potent neutralizing antibody response, increased G protein- and M2- specific T cell responses, and a reduction in RSV disease pathogenesis.

Intervertebral disc (IVD) is the fibrocartilage between the vertebrae, allowing the spine to move steadily by bearing multidirectional complex loads. Aging or injury usually causes degeneration of IVD, which is one of the main reasons for low back pain prevalent worldwide and reduced quality of life. While various treatment strategies for degenerative IVD have been studied using in vitro studies, animal experiments, and clinical trials, there are unsolved limitations for endogenous regeneration of degenerative IVD. In this respect, several tissue engineering strategies that are based on the cell and scaffolds have been extensively researched with positive outcomes for regeneration of IVD tissues. Scaffolds made of functional polymers and their diverse forms mimicking the macro- and micro-structure of native IVD enhance the biological and mechanical properties of the scaffolds for IVD regeneration. In this review, we discuss diverse morphological and functional polymers and tissue engineering strategies for endogenous regeneration of degenerative IVD. Tissue engineering strategies using functional polymers are promising therapeutics for fundamental and endogenous regeneration of degenerative IVD.