Vaccines2014, 2(4), 832-840; doi:10.3390/vaccines2040832 (registering DOI) - published 26 November 2014 Show/Hide Abstract
Abstract: Vaccines are commonly used as a preventive medicine for infectious diseases worldwide; however, the trial for an amyloid beta vaccine against Alzheimer’s disease will open a new concept in vaccination. In case of therapeutic vaccines for cancer, their targets are usually specific antigens in cancer cells, allowing activated cytotoxic T cells (CTLs) to attach and remove the antigen-presenting cancer cells. In our therapeutic vaccines against hypertension, the target is angiotensin II (Ang II) and induced anti-Ang II antibodies could efficiently ameliorate high blood pressure. Similarly, we developed the therapeutic vaccine against DPP4 for diabetes mellitus. However, because Ang II or DPP4 is an endogenous hormone, we must avoid autoimmune disease induced by these vaccines. Therefore, our system was used to design a therapeutic vaccine that elicits anti-Ang II or DPP4 antibodies without CTL activation against Ang II or DPP4. In this review, we will describe our concept of therapeutic vaccines for hypertension and diabetes mellitus.
Abstract: Equine influenza (EI) is a major respiratory disease of horses, which is still causing substantial outbreaks worldwide despite several decades of surveillance and prevention. Alongside quarantine procedures, vaccination is widely used to prevent or limit spread of the disease. The panel of EI vaccines commercially available is probably one of the most varied, including whole inactivated virus vaccines, Immuno-Stimulating Complex adjuvanted vaccines (ISCOM and ISCOM-Matrix), a live attenuated equine influenza virus (EIV) vaccine and a recombinant poxvirus-vectored vaccine. Several other strategies of vaccination are also evaluated. This systematic review reports the advances of EI vaccines during the last few years as well as some of the mechanisms behind the inefficient or sub-optimal response of horses to vaccination.
Abstract: This special issue is focused on DNA vaccines, marking the two decades since the first demonstration of pre-clinical protection was published in Science (Ulmer et al.; Heterologous protection against influenza by injection of DNA encoding a viral protein. 1993). This introductory article provides an overview of the field and highlights the observations of the articles in this special issue while placing them in the context of other recent publications.
Abstract: In previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses (rRCN) expressing Yersinia pestis antigens (F1 and V307—a truncated version of the V protein) provided superior protection against plague challenge compared to individual single antigen constructs. To reduce costs of vaccine production and facilitate implementation of a sylvatic plague vaccine (SPV) control program for prairie dogs, a dual antigen construct is more desirable. Here we report the construction and characterization of a novel RCN-vectored vaccine that simultaneously expresses both F1 and V307 antigens. This dual antigen vaccine provided similar levels of protection against plague in both mice and prairie dogs as compared to simultaneous administration of the two single antigen constructs and was also shown to protect mice against an F1 negative strain of Y. pestis. The equivalent safety, immunogenicity and efficacy profile of the dual RCN-F1/V307 construct warrants further evaluation in field efficacy studies in sylvatic plague endemic areas.
Abstract: The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8+ T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8∆ expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8+ T-cells. Thus, the safety and efficacy of LC16m8∆ mean that it represents an outstanding platform for the development of human vaccine vectors.
Abstract: Dendritic cells (DC) play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA) carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitroand in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future.