Viral vectors are promising tools for gene therapy and vaccines. Viral vector-based vaccines can enhance immunogenicity without an adjuvant and induce a robust cytotoxic T lymphocyte (CTL) response to eliminate virus-infected cells. During the last several decades, many types of viruses have been developed as vaccine vectors. Each has unique features and parental virus-related risks. In addition, genetically altered vectors have been developed to improve efficacy and safety, reduce administration dose, and enable large-scale manufacturing. To date, both successful and unsuccessful results have been reported in clinical trials. These trials provide important information on factors such as toxicity, administration dose tolerated, and optimized vaccination strategy. This review highlights major viral vectors that are the best candidates for clinical use.
The induction of T cell-mediated immunity is crucial in vaccine development. The most effective vaccine is likely to employ both cellular and humoral immune responses. The efficacy of a vaccine depends on T cells activated by antigen-presenting cells. T cells also play a critical role in the duration and cross-reactivity of vaccines. Moreover, pre-existing T-cell immunity is associated with a decreased severity of infectious diseases. Many technical and delivery platforms have been designed to induce T cell-mediated vaccine immunity. The immunogenicity of vaccines is enhanced by controlling the kinetics and targeted delivery. Viral vectors are attractive tools that enable the intracellular expression of foreign antigens and induce robust immunity. However, it is necessary to select an appropriate viral vector considering the existing anti-vector immunity that impairs vaccine efficacy. mRNA vaccines have the advantage of rapid and low-cost manufacturing and have been approved for clinical use as COVID-19 vaccines for the first time. mRNA modification and nanomaterial encapsulation can help address mRNA instability and translation efficacy. This review summarizes the T cell responses of vaccines against various infectious diseases based on vaccine technologies and delivery platforms and discusses the future directions of these cutting-edge platforms.
Adenoviruses are non-enveloped DNA viruses that cause a wide range of symptoms, from mild infections to life-threatening diseases in a broad range of hosts. Due to the unique characteristics of these viruses, they have also become a vehicle for gene-transfer and cancer therapeutic instruments. Adenovirus vectors can be used in gene therapy by modifying wild-type viruses to render them replication-defective. This makes it possible to swap out particular viral genes for segments that carry therapeutic genes and to employ the resultant vector as a means of delivering genes to specified tissues. In this review, we outline the progressive development of adenovirus vectors, exploring their characteristics, genetic modifications, and range of uses in clinical and preclinical settings. A significant emphasis is placed on their crucial role in advancing gene therapy, cancer therapy, immunotherapy, and the latest breakthroughs in vaccine development for various diseases.
Oncoprotein E6 of high-risk human papillomavirus (HPV) plays a critical role in inducing cell immortalization and malignancy. E6 downregulates caspase-dependent pathway through the degradation of p53. However, the effect of HPV E6 on other pathways is still under investigation. In the present study, we found that HPV E6 directly binds to all three forms (precursor, mature, and apoptotic) of apoptosis-inducing factor (AIF) and co-localizes with apoptotic AIF. This binding induced MG132-sensitive reduction of AIF expression in the presence of E6 derived from HPV16 (16E6), a cancer-causing type of HPV. Conversely, E6 derived from a non-cancer-causing type of HPV, HPV6 (6E6), did not reduce the levels of AIF despite its interaction with AIF. Flow cytometric analysis revealed that 16E6, but not 6E6, suppressed apoptotic AIF-induced chromatin degradation (an indicator of caspase-independent apoptosis) and staurosporine (STS, a protein kinase inhibitor)-induced apoptosis. AIF knockdown reduced STS-induced apoptosis in both of 16E6-expressing and 6E6-expressing cells; however, the reduction in 16E6-expressing cells was lower than that in 6E6-expressing cells. These findings indicate that 16E6, but not 6E6, blocks AIF-mediated apoptosis, and that AIF may represent a novel therapeutic target for HPV-induced cervical cancer.
Foot-and-mouth disease (FMD) is a highly contagious transboundary disease prevalent across the Asian continent, affecting both wild and domestic artiodactyls. The disease is caused by a virus belonging to the Aphthovirus genus of the Picornaviridae family which is categorized into seven serotypes: C, O, A, SAT1, SAT2, SAT3, and Asia1. The virus spreads through direct and indirect contact, including semen, meat, fomites, ingestion, and aerosols. FMD has a severe economic impact due to the high morbidity and mortality, especially in young animals. Prevention of the disease relies on vaccination with the prevalent serotype(s) or the slaughter and destruction of affected animals. This review discusses the prevalence of various FMD virus (FMDV) serotypes across Asia, along with the transmission modes, pathogenesis, immune response, and immune suppression by FMDV. Additionally, the review explores FMD diagnosis, prevention, and control strategies, and highlights future opportunities for research aimed at developing strain-specific viral and bacterial combined vaccines.