title: Exploring mucosal immunization with a recombinant influenza virus carrying an HIV-polyepitope in mice with pre-existing immunity to influenza.
abstract: HIV-1 vaccines based on recombinant vectors have been developed to elicit immune responses; however, the failure of the STEP HIV-1 vaccine trial has caused concern regarding the impact on vaccine efficacy of pre-existing vector seropositivity in humans. By using a mouse model of infection, we evaluated the immune responses elicited by intranasal and vaginal immunization with the recombinant influenza virus WSN/CKG carrying the PCLUS3-P18 peptide and a Gag epitope in its hemagglutinin, and the impact of pre-existing vector immunity on protection against recombinant vaccinia virus challenge. We found that despite the protective immunity induced in naïve mice by the WSN/CKG virus via either route, the vaginal immunization of mice with pre-existing influenza immunity restricted vPE16 replication more significantly in the ovaries than intranasal immunization. Thus, successful vaccination strategies under limiting conditions, such as pre-existing vector immunity, require the local induction of mucosal immunity at the site of virus infection.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy; Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome 00185 Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Garulli
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Mario
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Stillitano
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA; Division of Virology, Department of Microbiology and Immunology, and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Japan; Infection-Induced Host Responses Project, Exploratory Research for Advanced Technology, Saitama 332-0012, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy. Electronic address: mariarita.castrucci@iss.it.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Castrucci
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000281:Administration, Intranasal; D000282:Administration, Intravaginal; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae; D011994:Recombinant Proteins / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D000939:Epitopes; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic
keywords: AIDS vaccine; CD8+ T cell responses; Mucosal immunity; Pre-existing antibody; Viral vector