title: Adjuvant-like effect of vaccinia virus 14K protein: a case study with malaria vaccine based on the circumsporozoite protein.
abstract: Development of subunit vaccines for malaria that elicit a strong, long-term memory response is an intensive area of research, with the focus on improving the immunogenicity of a circumsporozoite (CS) protein-based vaccine. In this study, we found that a chimeric protein, formed by fusing vaccinia virus protein 14K (A27) to the CS of Plasmodium yoelii, induces strong effector memory CD8(+) T cell responses in addition to high-affinity Abs when used as a priming agent in the absence of any adjuvant, followed by an attenuated vaccinia virus boost expressing CS in murine models. Moreover, priming with the chimeric protein improved the magnitude and polyfunctionality of cytokine-secreting CD8(+) T cells. This fusion protein formed oligomers/aggregates that led to activation of STAT-1 and IFN regulatory factor-3 in human macrophages, indicating a type I IFN response, resulting in NO, IL-12, and IL-6 induction. Furthermore, this vaccination regimen inhibited the liver stage development of the parasite, resulting in sterile protection. In summary, we propose a novel approach in designing CS based pre-erythrocytic vaccines against Plasmodium using the adjuvant-like effect of the immunogenic vaccinia virus protein 14K.
authors.affiliation: Departamento de Biología Celular y Molecular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, 28049 Madrid, Spain.
authors.forename: Aneesh
authors.initials: A
authors.lastname: Vijayan
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Gómez
authors.forename: Diego A
authors.initials: DA
authors.lastname: Espinosa
authors.forename: Alan G
authors.initials: AG
authors.lastname: Goodman
authors.forename: Lucas
authors.initials: L
authors.lastname: Sanchez-Sampedro
authors.forename: Carlos Oscar S
authors.initials: CO
authors.lastname: Sorzano
authors.forename: Fidel
authors.initials: F
authors.lastname: Zavala
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000138:chemical synthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D015800:Protozoan Proteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014616:Vaccinia virus / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C041595:circumsporozoite protein, Protozoan