Strategies to improve the immunogenicity of prM+E dengue virus type-2 DNA vaccine.
Asian Pac J Allergy Immunol
; 35(1): 11-19, 2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-27001660
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.
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas do Envelope Viral
/
Vacinas contra Dengue
/
Anticorpos Antivirais
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article