A tetravalent recombinant dengue domain III protein vaccine stimulates neutralizing and enhancing antibodies in mice.
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.
Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Olivia K T
OK
Block
W W Shanaka I
WW
Rodrigo
Matthew
M
Quinn
Xia
X
Jin
Robert C
RC
Rose
Jacob J
JJ
Schlesinger
D000818:Animals; D019138:Antibodies, Blocking / Q000097:blood*; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D022223:Vaccines, Subunit / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D019138:Antibodies, Blocking; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins