title: NYVAC vector modified by C7L viral gene insertion improves T cell immune responses and effectiveness against leishmaniasis.
abstract: The NYVAC poxvirus vector is used as vaccine candidate for HIV and other diseases, although there is only limited experimental information on its immunogenicity and effectiveness for use against human pathogens. Here we defined the selective advantage of NYVAC vectors in a mouse model by comparing the immune responses and protection induced by vectors that express the LACK (Leishmania-activated C-kinase antigen), alone or with insertion of the viral host range gene C7L that allows the virus to replicate in human cells. Using DNA prime/virus boost protocols, we show that replication-competent NYVAC-LACK that expresses C7L (NYVAC-LACK-C7L) induced higher-magnitude polyfunctional CD8(+) and CD4(+) primary adaptive and effector memory T cell responses (IFNγ, TNFα, IL-2, CD107a) to LACK antigen than non-replicating NYVAC-LACK. Compared to NYVAC-LACK, the NYVAC-LACK-C7L-induced CD8(+) T cell population also showed higher proliferation when stimulated with LACK antigen. After a challenge by subcutaneous Leishmania major metacyclic promastigotes, NYVAC-LACK-C7L-vaccinated mouse groups showed greater protection than the NYVAC-LACK-vaccinated group. Our results indicate that the type and potency of immune responses induced by LACK-expressing NYVAC vectors is improved by insertion of the C7L gene, and that a replication-competent vector as a vaccine renders greater protection against a human pathogen than a non-replicating vector.
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Sánchez-Sampedro
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Mejías-Pérez
authors.affiliation: Biocomputing Unit, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: Carlos Óscar
authors.initials: CÓ
authors.lastname: S Sorzano
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Nájera
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain. Electronic address: mesteban@cnb.csic.es.
authors.forename: M
authors.initials: M
authors.lastname: Esteban
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D018320:Leishmania major / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000469:parasitology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology; D014779:Virus Replication; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000953:Antigens, Protozoan; D007371:Interferon-gamma; D007376:Interleukin-2; D054332:Leishmaniasis Vaccines; D051907:Lysosomal Membrane Proteins; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; C082283:C7L protein, Vaccinia virus; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C093139:LACK antigen, Leishmania
keywords: C7L; LACK; Leishmania; NYVAC; Vaccine; Vaccinia virus