title: Prime-boost immunization strategies against Chikungunya virus.
abstract: Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development and testing of novel DNA replicon and protein CHIKV vaccine candidates and evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous and heterologous prime-boost immunization strategies using novel and previously developed CHIKV vaccine candidates. Immunogenicity and efficacy were studied in a mouse model of CHIKV infection and showed that the DNA replicon and protein antigen were potent vaccine candidates, particularly when used for priming and boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral and cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine candidates and immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies and will form the basis for further preclinical and clinical evaluation of these vaccine candidates.
  
  
  OBJECTIVE
  As of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine candidates, a vaccine that could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully understand the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different candidates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine candidates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden david.hallengard@ki.se peter.liljestrom@ki.se.
authors.forename: David
authors.initials: D
authors.lastname: Hallengärd
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.
authors.forename: Fok-Moon
authors.initials: FM
authors.lastname: Lum
authors.affiliation: University of Bonn Medical Centre, Bonn, Germany.
authors.forename: Beate M
authors.initials: BM
authors.lastname: Kümmerer
authors.affiliation: Institute of Technology, University of Tartu, Tartu, Estonia.
authors.forename: Aleksei
authors.initials: A
authors.lastname: Lulla
authors.affiliation: Institute of Technology, University of Tartu, Tartu, Estonia.
authors.forename: Valeria
authors.initials: V
authors.lastname: Lulla
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: García-Arriaza
authors.affiliation: Institute of Virology, The Pirbright Institute, Pirbright, United Kingdom.
authors.forename: John K
authors.initials: JK
authors.lastname: Fazakerley
authors.affiliation: Division of Immuno-Virology, iMETI, CEA, Paris, France UMR-E1, University Paris-Sud XI, Orsay, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roques
authors.affiliation: Division of Immuno-Virology, iMETI, CEA, Paris, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.affiliation: Institute of Technology, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Merits
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore.
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden david.hallengard@ki.se peter.liljestrom@ki.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Liljeström
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D065632:Chikungunya Fever / Q000276:immunology / Q000517:prevention & control*; D002646:Chikungunya virus / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines