Evaluation of Interferences between Dengue Vaccine Serotypes in a Monkey Model

被引:119
作者
Guy, Bruno [1 ]
Barban, Veronique
Mantel, Nathalie
Aguirre, Marion
Gulia, Sandrine
Pontvianne, Jeremy
Jourdier, Therese-Marie
Ramirez, Laurence
Gregoire, Veronique
Charnay, Christophe
Burdin, Nicolas
Dumas, Rafaele
Lang, Jean
机构
[1] Sanofi Pasteur, Res Dept, F-69280 Marcy Letoile, France
关键词
CLINICAL LABORATORY RESPONSES; YELLOW-FEVER; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; IMMUNOGENICITY; SAFETY; FORMULATIONS; INFECTION; IMMUNIZATION; PATHOGENESIS;
D O I
10.4269/ajtmh.2009.80.302
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
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 I-year booster. The applicability of these data to human responses is discussed.
引用
收藏
页码:302 / 311
页数:10
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