Virology & Mycology
Open Access

Serotype-specificity and immunogenicity of domain-swapped Virus Like Particles (VLPs) from dengue virus serotypes 1 and 2

10^th World Congress on Virology and Mycology

May 11-12, 2017 Singapore

Gielenny M Salem, Jedhan U Galula, Leslie Michelle M Dalmacio and Day-Yu Chao

University of the Philippines Manila, Philippines
National Chung Hsing University, Taiwan

Posters & Accepted Abstracts: Virol-mycol

Abstract :

The dengue virus (DENV) remains the most important and rapidly emerging mosquito-borne pathogen worldwide. While humans develop long-lived, strongly neutralizing antibodies (NtAbs) after initial or primary dengue infection, there is conflicting information on the specific targets of NtAbs on the envelope (E) glycoprotein, which confounds the development of more effective vaccines. To determine the specific target/s of NtAbs against DENV 1 and 2, we used dengue virus-like particles (VLP) consisting of E domains I/II and III from DENV type 1 (D1) and type 2 (D2) to produce two domain-swapped VLPs (D2-D1 I/II and D2-D1 III) and two parental VLPs (D1 and D2). DNA plasmid vaccine expressing the E proteins of parental and domain-swapped VLPs were intramuscularly administered to 25 female BALB/c mice, divided into five groups at three 4-week intervals. The dengue VLPs and DNA vaccines were characterized through immunofluorescence assay (IFA), antigen-capture (Ag-capture) ELISA and SDSPAGE. IFA detected that the parental and domain-swapped VLPs were intracellularly produced in COS-1 cells. SDS-PAGE confirmed the expected VLP structure and showed that the VLPs have comparable maturation states. Ag-capture ELISA showed that mice vaccinated with parental and domain-swapped (D2-D1 I/II) VLPs produced cross-reactive antibodies targeting different E domains (interdomain) and broad and high neutralization titers against DENV1 Hawaii. On the other hand, mice immunized with D2 and domain swapped VLPs generated type-specific and high neutralizing titers against DENV2 16681. This implies that the protective ability of immune mice sera against DENVs is serotype-dependent. Interestingly, there is loss of neutralization against DENV1 Hawaii in D2-D1 III immunized sera, suggesting that domain I/II determines the serotypespecificity of NtAbs. ELISA and focus reduction microneutralization test (FR�?¼NT) showed that the domain-swapped VLP antigens can be used to determine the dengue serotype in primary infection. Knowledge on the character and immunogenicity of the VLPs will lead to the development of nextgeneration, antigen-specific dengue vaccines.

Biography :

Email: gielennymsalem@yahoo.com.ph