DNA vaccines against dengue virus based on the ns1 gene: The influence of different signal sequences on the protein expression and its correlation to the immune response elicited in mice

Abstract We analyzed four DNA vaccines based on DENV-2 NS1: pcENS1, encoding the C-terminal from E protein plus the NS1 region; pcENS1ANC, similar to pcENS1 plus the N-terminal sequence from NS2a (ANC); pcTPANS1, coding the t-PA signal sequence fused to NS1; and pcTPANS1ANC, similar to pcTPANS1 plus...

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Bibliographic Details
Published in:	Virology (New York, N.Y.) Vol. 358; no. 2; pp. 413 - 423
Main Authors:	Costa, S.M, Azevedo, A.S, Paes, M.V, Sarges, F.S, Freire, M.S, Alves, A.M.B
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 20-02-2007
Subjects:	Animals Antibodies, Viral - blood Antigens, Viral - genetics Antigens, Viral - immunology Antigens, Viral - metabolism Challenge dengue Dengue - immunology Dengue - prevention & control Dengue Vaccines - administration & dosage Dengue Vaccines - genetics Dengue virus Dengue Virus - immunology disease prevention DNA vaccine DNA vaccines gene expression glycoproteins human health immune response Immunization Infectious Disease Injections, Intramuscular Mice Mice, Inbred BALB C Mouse NS1 Plasmids - genetics plasminogen activator Plasminogen Activators - genetics recombinant vaccines signal peptide Vaccines, DNA - administration & dosage Vaccines, DNA - genetics viral envelope proteins Viral Envelope Proteins - genetics Viral Envelope Proteins - immunology viral nonstructural proteins Viral Nonstructural Proteins - genetics Viral Nonstructural Proteins - immunology Viral Nonstructural Proteins - metabolism viral proteins DNA vaccine Mouse Dengue virus NS1 Challenge
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Summary:	Abstract We analyzed four DNA vaccines based on DENV-2 NS1: pcENS1, encoding the C-terminal from E protein plus the NS1 region; pcENS1ANC, similar to pcENS1 plus the N-terminal sequence from NS2a (ANC); pcTPANS1, coding the t-PA signal sequence fused to NS1; and pcTPANS1ANC, similar to pcTPANS1 plus the ANC sequence. The NS1 was detected in lysates and culture supernatants from pcTPANS1-, pcENS1- and pcENS1ANC-transfected cells and not in cells with pcTPANS1ANC. Only the pcENS1ANC leads the expression of NS1 in plasma membrane, confirming the importance of ANC sequence for targeting NS1 to cell surface. High levels of antibodies recognizing conformational epitopes of NS1 were induced in mice immunized with pcTPANS1 and pcENS1, while only few pcENS1ANC-inoculated animals presented detectable anti-NS1 IgG. Protection against DENV-2 was verified in pcTPANS1- and pcENS1-immunized mice, although the plasmid pcTPANS1 induced slight higher protective immunity. These plasmids seem to activate distinct patterns of the immune system.
Bibliography:	http://dx.doi.org/10.1016/j.virol.2006.08.052 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0042-6822 1096-0341
DOI:	10.1016/j.virol.2006.08.052