title: An adenoviral vector expressing lipoprotein A, a major antigen of Mycoplasma mycoides subspecies mycoides, elicits robust immune responses in mice.
abstract: Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides small colony type (MmmSC), is a devastating respiratory disease of cattle. In sub-Saharan Africa, where CBPP is enzootic, live attenuated vaccines are deployed but afford only short-lived protection. In cattle, recovery from experimental MmmSC infection has been associated with the presence of CD4(+) T lymphocytes that secrete interferon gamma in response to MmmSC, and in particular to the lipoprotein A (LppA) antigen. In an effort to develop a better vaccine against CBPP, a viral vector (Ad5-LppA) that expressed LppA was generated from human adenovirus type 5. The LppA-specific immune responses elicited by the Ad5-LppA vector were evaluated in mice, and compared to those elicited by recombinant LppA formulated with a potent adjuvant. Notably, a single administration of Ad5-LppA, but not recombinant protein, sufficed to elicit a robust LppA-specific humoral response. After a booster administration, both vector and recombinant protein elicited strong LppA-specific humoral and cell-mediated responses. Ex vivo stimulation of splenocytes induced extensive proliferation of CD4(+) T cells for mice immunized with vector or protein, and secretion of T helper 1-associated and proinflammatory cytokines for mice immunized with Ad5-LppA. Our study - by demonstrating the potential of a viral-vectored prototypic vaccine to elicit prompt and robust immune responses against a major antigen of MmmSC - represents a first step in developing a recombinant vaccine against CBPP.
authors.affiliation: Centre International de Recherche en Agronomie pour le Développement, UMR CMAEE, Montpellier, France; INRA, UMR 1309 CMAEE, Montpellier, France; INRA, UMR 1161 Virologie, 7 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; ANSES, UMR Virologie, 23 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, UMR Virologie, Maisons-Alfort F-94704, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Carozza
authors.affiliation: Centre International de Recherche en Agronomie pour le Développement, UMR CMAEE, Montpellier, France; INRA, UMR 1309 CMAEE, Montpellier, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Rodrigues
authors.affiliation: INRA, UMR 1161 Virologie, 7 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; ANSES, UMR Virologie, 23 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, UMR Virologie, Maisons-Alfort F-94704, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Unterfinger
authors.affiliation: INRA, UMR 1161 Virologie, 7 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; ANSES, UMR Virologie, 23 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, UMR Virologie, Maisons-Alfort F-94704, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Galea
authors.affiliation: INRA, UMR 1161 Virologie, 7 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; ANSES, UMR Virologie, 23 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, UMR Virologie, Maisons-Alfort F-94704, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Coulpier
authors.affiliation: INRA, UMR 1161 Virologie, 7 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; ANSES, UMR Virologie, 23 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, UMR Virologie, Maisons-Alfort F-94704, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Klonjkowski
authors.affiliation: Centre International de Recherche en Agronomie pour le Développement, UMR CMAEE, Montpellier, France; INRA, UMR 1309 CMAEE, Montpellier, France.
authors.forename: François
authors.initials: F
authors.lastname: Thiaucourt
authors.affiliation: Centre International de Recherche en Agronomie pour le Développement, UMR CMAEE, Montpellier, France; INRA, UMR 1309 CMAEE, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Totté
authors.affiliation: INRA, UMR 1161 Virologie, 7 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; ANSES, UMR Virologie, 23 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, UMR Virologie, Maisons-Alfort F-94704, France. Electronic address: jrichardson@vet-alfort.fr.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Richardson
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D017270:Lipoprotein(a) / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009176:Mycoplasma mycoides / Q000235:genetics / Q000276:immunology*; D011002:Pleuropneumonia, Contagious / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D004337:Drug Carriers; D017270:Lipoprotein(a)
keywords: Adenovirus type 5; Contagious bovine pleuropneumonia; Mycoplasma mycoides subspecies mycoides