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Evaluation of Interferences between Dengue Vaccine Serotypes in a Monkey Model

Bruno GuyResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Veronique BarbanResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Nathalie MantelResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Marion AguirreResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Sandrine GuliaResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Jeremy PontvianneResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Therese-Marie JourdierResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Laurence RamirezResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Veronique GregoireResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Christophe CharnayResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Nicolas BurdinResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Rafaele DumasResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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Jean LangResearch and Discovery Departments, Sanofi Pasteur, Marcy l’Etoile, France

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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.

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