A DNA vaccine against chikungunya virus is protective in mice - induces neutralizing antibodies in mice and nonhuman primates
Autor(es): Mallilankaraman Karthik, Shedlock Devon J, Bao Huihui, Kawalekar Omkar U, Fagone Paolo, Ramanathan Aarthi A, Ferraro Bernadette, Stabenow Jennifer, Vijayachari Paluru, Sundaram Senthil G, Muruganandam Nagarajan, Sarangan Gopalsamy, Srikanth Padma, Khan Amir S, Lewis Mark G, Kim J Joseph, Sardesai Niranjan Y, Muthumani Karuppiah, Weiner David B
Resumo: Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus indigenous to tropical Africa - Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, - sometimes arthritis. Relatively little is known about the antigenic targets for immunity, - no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. - Europe. Considering the potential for p-emic spread, underst-ing the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient - developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis - develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP) that expresses a component of the CHIKV envelope glycoprotein - used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular - humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease - support further study of envelope-based CHIKV DNA vaccines.
Imprenta: PLoS Neglected Tropical Diseases, v. 5, n. 1, p. e928, 2011
Identificador do objeto digital: 10.1371/journal.pntd.0000928
Descritores: Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2011
