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

• Published in: Vaccine Vol. 28; no. 51; pp. 8085 - 8094
• Main Authors: Block, Olivia K.T, Rodrigo, W.W. Shanaka I, Quinn, Matthew, Jin, Xia, Rose, Robert C, Schlesinger, Jacob J
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 29.11.2010; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Antibodies, Blocking - blood; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Applied microbiology; Arboviroses; Biological and medical sciences; Dengue; Dengue fevers; Dengue Vaccines - immunology; Dengue Virus - immunology; Domain III; Enhancement; Female; Fundamental and applied biological sciences. Psychology; Human viral diseases; Immunization; Immunoglobulin G - blood; Infectious diseases; Medical research; Medical sciences; Mice; Mice, Inbred BALB C; Microbiology; Proteins; Tropical viral diseases; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Subunit - immunology; Vector-borne diseases; Viral diseases; Viral Envelope Proteins - immunology; Viruses; Domain III; Vaccine; Enhancement; Dengue; Rodentia; Enhancing antibody; Neutralizing antibody; Infection; Vertebrata; Mammalia; Mouse; Viral disease; Arbovirus disease; Recombinant protein
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.10.004

Abstract 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 FcγR-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.