A tetravalent recombinant dengue domain III protein vaccine stimulates neutralizing and enhancing antibodies in mice

作者：Block Olivia K T; Rodrigo W W Shanaka I; Quinn Matthew; Jin Xia; Rose Robert C; Schlesinger Jacob J^*

来源：Vaccine, 2010, 28(51): 8085-8094.

DOI：10.1016/j.vaccine.2010.10.004

• Dengue
• Domain III
• Vaccine
• Enhancement

Dengue viruses co-circulate as four serologically distinct viruses (DENV1-4) that commonly infect individuals sequentially. Current DENV candidate vaccines incorporate the entire virion envelope E protein (E) ectodomain thereby stimulating both DENV serotype-specific and cross-reactive antibodies. Because the latter may enhance naturally acquired infection, such vaccine formulations must be tetravalent. We evaluated the neutralizing and enhancing antibody response to E domain III (dIII) proteins, in which serotype-specific neutralizing determinants are concentrated. Mice immunized with insect cell-secreted recombinant DENV-dIII proteins individually, and in tetravalent combination, produced serotype-specific IgG1 neutralizing antibodies that nevertheless exhibited measurable DENV enhancing activity in Fc gamma R-bearing cells. Vaccine strategies directed to DENV-dIII-targeted neutralizing antibody production remain attractive but will likely require further modifications to induce safe, protective immunity.

• 出版日期2010-11-29