title: Deciphering the protective role of adaptive immunity to CHIKV/IRES a novel candidate vaccine against Chikungunya in the A129 mouse model.
abstract: Chikungunya virus (CHIKV), a mosquito-borne alphavirus, recently re-emerged in Africa and spread to islands in the Indian Ocean, the Indian subcontinent, and to South East Asia. Viremic travelers have also imported CHIKV to the Western hemisphere highlighting the importance of CHIKV in public health. In addition to the great burden of arthralgic disease, which can persist for months or years, epidemiologic studies have estimated case-fatality rates of ∼0.1%, principally from neurologic disease in older patients. There are no licensed vaccines or effective therapies to prevent or treat human CHIKV infections. We have developed a live CHIKV vaccine (CHIKV/IRES) that is highly attenuated yet immunogenic in mouse models, and is incapable of replicating in mosquito cells. In this study we sought to decipher the role of adaptive immunity elicited by CHIKV/IRES in protection against wild-type CHIKV infection. A single dose of vaccine effectively activated T cells with an expansion peak on day 10 post immunization and elicited memory CD4(+) and CD8(+) T cells that produced IFN-γ, TNF-α and IL-2 upon restimulation with CHIKV/IRES. Adoptive transfer of CHIKV/IRES-immune CD4(+) or CD8(+) T cells did not confer protection against wtCHIKV-LR challenge. By contrast, passive immunization with anti-CHIKV/IRES immune serum provided protection, and a correlate of a minimum protective neutralizing antibody titer was established. Overall, our findings demonstrate the immunogenic potential of the CHIKV/IRES vaccine and highlight the important role that neutralizing antibodies play in protection against an acute CHIKV infection.
authors.affiliation: Inviragen, Inc., Madison, WI 53719, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.forename: Subash C
authors.initials: SC
authors.lastname: Das
authors.forename: Jeremy F
authors.initials: JF
authors.lastname: Fuchs
authors.forename: M
authors.initials: M
authors.lastname: Suresh
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.forename: Dan T
authors.initials: DT
authors.lastname: Stinchcomb
authors.forename: Charalambos D
authors.initials: CD
authors.lastname: Partidos
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D018354:Alphavirus Infections / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D065632:Chikungunya Fever; D002646:Chikungunya virus; D004195:Disease Models, Animal; D005260:Female; D007106:Immune Sera / Q000276:immunology; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D057507:Mice, 129 Strain; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007106:Immune Sera; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D007371:Interferon-gamma
keywords: A129 mice; Cellular immunity; Chikungunya (CHIKV); Humoral immunity; Interferon (IFN); Protection