title: Could an experimental dengue virus infection fail to induce solid immunity against homologous viral challenge in non-human primates?
abstract: There are several dengue vaccine candidates at advanced stages of development, but none of them are licensed. Despite the reactogenicity and immunogenicity profile in humans of the tetravalent ChimeriVax™ dengue vaccine candidate, in efficacy trials, it has failed to confer complete protection against dengue virus (DENV)-1 and DENV-2. However, full protection against the four serotypes had been observed previously in monkeys immunized with this vaccine candidate. Some authors have tried to explain this contradiction by hypothesizing that protection rates in non-human primates (NHPs) are associated with a lack of post-challenge anamnestic immune responses. Here, we studied the protection and anamnestic response patterns after homologous challenge in NHPs previously infected with DENV-2. Two immunization schemes were used, varying the viral doses and the intervals between them. Animals developed immunity against DENV-2 that provided full protection against reinfection with a homologous virus. However, all monkeys showed a significant increase in antiviral and neutralizing antibody titers after challenge. Our results suggest that sterilizing immunity could not be induced by infection with the virus despite the lack of detectable viremia in some animals in which an increase in antibody titer was observed. For this reason, we propose that the lack of an anamnestic neutralizing antibody response after challenge, as suggested by some authors, should be carefully reviewed as a criterion for evaluating the functionality of vaccine candidates.
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Iris
authors.initials: I
authors.lastname: Valdés
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba. lazaro.gil@cigb.edu.cu.
authors.forename: Lázaro
authors.initials: L
authors.lastname: Gil
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Laura
authors.initials: L
authors.lastname: Lazo
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Marcos
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Jorge
authors.initials: J
authors.lastname: Martín
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Edith
authors.initials: E
authors.lastname: Suzarte
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Jorge
authors.initials: J
authors.lastname: Castro
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Yaremis
authors.initials: Y
authors.lastname: Romero
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guillén
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba. lisset.hermida@cigb.edu.cu.
authors.forename: Lisset
authors.initials: L
authors.lastname: Hermida
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D003715:Dengue / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D003716:Dengue Virus / Q000276:immunology*; D007156:Immunologic Memory; D018419:Primate Diseases / Q000517:prevention & control*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
keywords: Dengue virus; Immunity; Non-human primates; Solid protection; Sterilizing immunity; Vaccine