dna疫苗
病毒学
生物
质粒
登革热病毒
重组DNA
登革热
表位
登革热疫苗
信号肽
抗体
病毒
基因
分子生物学
免疫学
遗传学
作者
Simoni Furtado da Costa,Marciano Viana Paes,Débora Ferreira Barreto,Angela Teixeira Pinhão,Ortrud Monika Barth,João Luiz Queiroz,Geraldo R. G. Armôa,Marcos S. Freire,Ada M. B. Alves
出处
期刊:Vaccine
[Elsevier]
日期:2006-01-01
卷期号:24 (2): 195-205
被引量:66
标识
DOI:10.1016/j.vaccine.2005.07.059
摘要
Dengue is one of the most important arboviral diseases in humans, and although efforts over the last decades have dealt with the development of a vaccine, this vaccine is not available yet. In order to evaluate the potential of a DNA vaccine based on the non-structural 1 (NS1) protein against dengue virus (DENV), we constructed the pcTPANS1 plasmid which contains the secretory signal sequence derived from human tissue plasminogen activator (t-PA) fused to the full length of the DENV-2 NS1 gene. Results indicate that pcTPANS1 promotes correct expression of NS1 in eukaryotic cells and drives secretion of the recombinant protein to the surrounding medium in a dimeric form. Balb/c mice, intramuscularly inoculated with this plasmid, presented high levels of antibodies, recognizing mainly surface-exposed conformational epitopes present in the NS1 protein expressed by insect cells. Long-term antibody response was observed in animals 56 weeks after the first plasmid inoculation, and a rapid, efficient secondary response was observed after a DNA boost. Vaccinated animals were challenged against DENV-2 in two murine models, based on intracerebral (i.c.) and intraperitoneal (i.p.) virus inoculations, and in both cases, pcTPANS1-immunized mice were protected. Overall, these results provide further support for the use of such a plasmid in a possible approach for the development of a vaccine against DENV.
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