Immunogenicity of Novel Consensus-Based DNA Vaccines Against Chikungunya Virus

Abstract

CHIKV is an emerging arbovirus and is an important human pathogen that causes a syndrome characterized by fever, headache, rash, nausea, vomiting, myalgia, arthralgia and occasionally neurological manifestations such as acute limb weakness. It is also associated with a fatal haemorrhagic condition. CHIKV is geographically distributed from Africa through Southeast Asia and South America, and its transmission to humans is mainly through Aedes species mosquitoes. The frequency of recent epidemics in the Indian Ocean islands suggests that something else was carrying the virus, as Aedes aegypti are not found there. In fact, the relative Asian tiger mosquito, Aedes albopictus, was present and has raised concern in the world health community regarding the potential for a CHIK virus pandemic. Efforts to monitor the disease will only provide minimal warning in a global society, and steps must be taken to prevent the morbidity and mortality associated with a possible pandemic. There is no specific treatment for Chikungunya virus and there is no vaccine currently available. We propose a novel consensus-based approach to vaccine development, employing a DNA vaccine strategy that can provide more highly cross-reactive cellular immunity against CHIK virus. The vaccine cassette was designed based on Capsid (Cap) and Envelope (E1) specific consensus sequences with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. The expression of Cap and envelope E1 was evaluated using T7-coupled transcription/translation and immuno blot analysis. A recently developed, adaptive constant-current electroporation technique was used to immunize mice (both Balb/C & C57BL/6 mice strain) with an intramuscular injection of plasmid coding for the CHICK-Cap and E1. We show such constructs can induce strong cellular immunity against CHIK-Cap and E1 antigens. The analysis of specific antibody responses suggested that CHIK-E1 could induce a strong E1 specific antibody response. Epitope mapping results indicated that there is an increase in the breadth and magnitude of cross-reactive cellular responses induced by both the Capsid and Envelope immunogen. These properties suggest that such a consensus immunogen deserves further examination for its potential to serve as a component antigen in a CHIK vaccine cocktail. 13th International Congress on Infectious Diseases Abstracts (Oral Presentations)International Journal of Infectious DiseasesVol. 12Preview Full-Text PDF Open Archive