Development of a CD8 T-Cell Priming Vaccine Against Chikungunya Virus

点击翻译按钮获取中文摘要

Chikungunya virus (CHIKV) imparts a high public health burden with more than a billion people living in endemic areas. CHICKV infection is spread to people by the bite of an infected mosquito. It is not often fatal but is very debilitating, with the potential for mother to child transmission. CHIKV. Outbreaks have occurred in countries in Africa, Asia, the Americas, the Indian and Pacific Oceans, and Europe. CHIKV is considered an emerging pathogen of concern because it poses a threat to temperate regions and there is a risk that the virus will be imported to new areas by infected travelers. The virus has been able to adapt to different mosquito vectors, and genetic analysis suggests that the increased severity of recent outbreaks may be due to viral mutation that enables the virus to multiply more easily in a mosquito vector. During outbreaks, due to the high concentration of virus in the blood of those in the acute phase of infection, the virus can readily circulate from humans to mosquitoes and back to humans. There is no vaccine to prevent or medicine to treat CHIKV infection.The proposed effort will generate a fully synthetic CD8 T-Cell priming vaccine candidate for human use. The vaccine will utilize an established platform comprised of two technologies: a combinatorial library of specific MHC Class 1-restricted viral peptides, and a self-adjuvating gold nanoparticle carrier (GNP) system. When combined, these technologies constitute a fully synthetic vaccine construct with a simple chemical synthesis, minimal cold chain requirements (stability demonstrated for \>3 months at ambient temperature) and is delivered subcutaneously using micro-needle patches. These characteristics enable rapid manufacturing and needle-free delivery by relatively untrained individuals in a diversity of low resourced care settings. Emergex has completed preclinical toxicology and initiated human clinical studies with several vaccine constructs utilizing the same technology.In contrast to the majority of antibody-stimulating vaccines, Emergex's vaccine strategy is to 'prime' CD8+ T 'killer' cells. The vaccine is designed to promote the natural cellular immune response to infection. A post-vaccination pathogen exposure is then rapidly met by virus-specific effector CD8 T-Cells, resulting in the killing of infected cells and preventing the ability to produce infectious virus particles that may contribute to disease transmission. This vaccine strategy is anticipated to provide decades-long immune memory, be less prone to viral escape mutation, and may offer 'cross reactive' immunity against more than one virus in the same family.