Evaluation of interferences between dengue vaccine serotypes in a monkey model.
Interferences between different antigens in the same vaccine formulation have been reported for some vaccines (e.g., polio vaccines, live attenuated dengue vaccine candidates). We examined interferences between the four serotypes of ChimeriVax dengue vaccines (CYDs) in a monkey model when present within a tetravalent formulation in equal concentrations (TV-5555). Immunoassays of vaccinated non-human primates showed that serotype 4 (DEN-4), and to a lesser extent, DEN-1 were dominant in terms of neutralizing antibody levels. Parameters that affected the interferences were identified, including 1) the simultaneous administration of two complementary bivalent vaccines at separate anatomical sites drained by different lymph nodes; 2) the sequential administration of two complementary bivalent vaccines; 3) the establishment of heterologous flavivirus pre-immunity before subsequent tetravalent immunization; 4) the adaptation of formulations by decreasing the dose of the immunodominant serotype; and 5) the administration of a 1-year booster. The applicability of these data to human responses is discussed.
Guy
Bruno
B
Research and Discovery Departments, Sanofi Pasteur, Marcy l'Etoile, France. bruno.guy@sanofipasteur.com
Barban
Veronique
V
Mantel
Nathalie
N
Aguirre
Marion
M
Gulia
Sandrine
S
Pontvianne
Jeremy
J
Jourdier
Therese-Marie
TM
Ramirez
Laurence
L
Gregoire
Veronique
V
Charnay
Christophe
C
Burdin
Nicolas
N
Dumas
Rafaele
R
Lang
Jean
J
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003715:Dengue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003716:Dengue Virus / Q000145:classification* / Q000276:immunology* / Q000472:pathogenicity; D004195:Disease Models, Animal; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008252:Macaca fascicularis; D008297:Male; D009500:Neutralization Tests; D012703:Serotyping; D014611:Vaccination; D014709:Vero Cells; D014762:Viral Interference; D014766:Viremia / Q000276:immunology / Q000517:prevention & control / Q000821:virology
D000914:Antibodies, Viral; D053059:Dengue Vaccines