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.
Block
Olivia K T
OK
Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Rodrigo
W W Shanaka I
WW
Quinn
Matthew
M
Jin
Xia
X
Rose
Robert C
RC
Schlesinger
Jacob J
JJ
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