Autor(es): Muthumani Karuppiah, Lankaraman Katthikbabu M, Laddy Dominick J, Sundaram Senthil G, Chung Christopher W, Sako Eric, Wu Ling, Khan Amir, Sardesai Niranjan, Kim Joseph J, Vijayachari Paluru, Weiner David B

Resumo: Chikungunya virus (CHIKV) is an emerging arbovirus - is an important human pathogen. Infection of humans by CHIKV can cause a syndrome characterized by fever, headache, rash, nausea, vomiting, myalgia, arthralgia - 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 - South America, - its transmission to humans is mainly through the Aedes aegypti species mosquitoes. The frequency of recent epidemics in the Indian Ocean - La Reunion isl-s suggests that a new vector perhaps is carrying the virus, as A. aegypti are not found there. In fact, a relative the Asian tiger mosquito, Aedes albopictus, may be the culprit which has raised concerns in the world health community regarding the potential for a CHIK virus p-emic. Accordingly steps should be taken to develop methods for the control of CHIKV. Unfortunately, currently there is no specific treatment for Chikungunya virus - there is no vaccine currently available. Here we present data of a novel consensus-based approach to vaccine design for CHIKV, employing a DNA vaccine strategy. The vaccine cassette was designed based on CHIKV capsid- - envelope-specific consensus sequences with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, - a substituted immunoglobulin E leader sequence. The expression of capsid, envelope E1 - E1 was evaluated using T7-coupled transcription/translation - immunoblot analysis. A recently developed, adaptive constant-current electroporation technique was used to immunize C57BL/6 mice with an intramuscular injection of plasmid coding for the CHIK-Capsid, E1 - E2. Analysis of cellular immune responses, including epitope mapping, demonstrates that electroporation of these constructs induces both potent - broad cellular immunity. In addition, antibody ELISAs demonstrate that these synthetic immunogens are capable of inducing high titer antibodies capable of recognizing native antigen. Taken together, these data support further study of the use of consensus CHIK antigens in a potential vaccine cocktail.

Palavras-Chave: Chikungunya virus (CHIKV); DNA vaccination; Envelope; Capsid; Electroporation

Imprenta: Vaccine, v. 26, n. 40, p. 5128-5134, 2008

Identificador do objeto digital: 10.1016/j.vaccine.2008.03.060

Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - DNA ; Chikungunya virus - Genome ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Antibodies ; Chikungunya virus - T lymphocytes ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Transmission ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology ; Chikungunya virus - Public health

Data de publicação: 2008

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