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Asian Pac J Allergy Immunol. 2017 Mar;35(1):11-19. doi: 10.12932/AP0728.

Strategies to improve the immunogenicity of prM+E dengue virus type-2 DNA vaccine.

Author information

1
Dengue Vaccine Research Unit, Chula Vaccine Research Center (Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
2
Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
3
Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
4
Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok, Thailand.
5
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
6
Biomedical Technology Research Center, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok, Thailand.
7
Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.
8
Vaccine and Cellular Immunology Laboratory, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Abstract

BACKGROUND:

An important goal for dengue vaccines is to induce a high and durable level of neutralizing antibody.

OBJECTIVE:

Three strategies were investigated for improving the immunogenicity of a prM+E dengue serotype 2 (DENV-2) DNA vaccine: 1) expression in two different plasmids; 2) adjustment of dose; and, 3) introduction of the E sequence of Japanese encephalitis virus (JEV) at the carboxy-terminal portion of DENV-2 E.

METHOD:

Expression cassettes were designed to encode a full-length prM+E sequence of DENV-2 virus employing human-preferred codons (D2prMEopt), or a chimeric prM+E sequence in which the 100-residue carboxy-terminal region of E was derived from JEV (D2prMEJE20opt). pHIS and pCMVkan in the presence and absence of CpG motif, respectively, were used for cassette expression. The immunogenicity was compared in mice.

RESULTS:

Three injections of full-length-D2prMEopt in pHIS and pCMVkan induced a comparable neutralizing antibody titer at post-week-2-injection and post-week-4-injection. The 100-μg DNA dose induced a numerically but not statistically higher neutralizing antibody titer than the 10-μg dose. The chimeric-D2prMEJE20opt produced higher extracellular prM and E protein levels in transfected Vero cells, but had a tendency to induce a lower neutralizing antibody titer in mice when compared with the full-length-D2prMEopt. To optimize the immunogenicity of D2prMEopt-DNA candidate, both expression plasmids can be used to generate reproducible high neutralizing titer. A higher dose of DNA immunogen may induce a higher neutralizing antibody response.

CONCLUSION:

The strategy of the C-terminal region chimeric counterpart with JE20 did not improve but may have reduced the induction of neutralizing antibodies.

PMID:
27001660
DOI:
10.12932/AP0728
[Indexed for MEDLINE]
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