Induction of neutralizing antibodies and T cell responses by dengue virus type 2 envelope domain III encoded by plasmid and adenoviral vectors.
Dengue is a re-emerging public health problem in many developing nations. There is neither a specific antiviral therapy to treat nor a licensed vaccine to prevent dengue infections. In recent years, the carboxy-terminal region of the major dengue virion envelope (E) protein, known as domain III, has emerged as a significant sub-unit vaccine candidate. In this study, we created a recombinant adenovirus capable of expressing the E domain III (EDIII) of dengue virus type 2 (DEN-2) and tested it in combination with a plasmid encoding the same domain to determine its potential as a possible dengue vaccine candidate. We examined the relative efficacies of plasmid prime/Ad boost (P/A) and Ad prime/plasmid boost (A/P) regimens in eliciting DEN-2 virus-specific immune responses. Both regimens resulted in the induction of antibodies that specifically bound to and neutralized the infectivity of DEN-2 virus. Splenocytes from immunized mice, stimulated in vitro, manifested a significant proliferative response accompanied by the production of high levels of interferon-gamma, but moderately elevated levels of interleukin-4, indicative of a predominantly Th1 type response. Based on a comparison of the parameters investigated, the immune response induced by the A/P regimen appeared to be relatively more potent. Our data suggest that EDIII may be valuable in the efforts to develop plasmid- and Ad-vectored dengue vaccines.
Khanam
Saima
S
International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
Khanna
Navin
N
Swaminathan
Sathyamangalam
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000096:biosynthesis / Q000276:immunology; D003716:Dengue Virus / Q000235:genetics* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006462:Hemolytic Plaque Technique; D008055:Lipids; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010957:Plasmids / Q000235:genetics* / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology*
D000914:Antibodies, Viral; D016207:Cytokines; D004279:DNA, Viral; C051821:E-glycoprotein, Dengue virus type 2; D008055:Lipids; C086724:Lipofectamine; D014759:Viral Envelope Proteins; D014765:Viral Vaccines