title: Enhancement of T cell-mediated immune responses to whole inactivated influenza virus by chloroquine treatment in vivo.
abstract: Current influenza vaccines induce poor cross-reactive CD8+ T cell responses. Cellular immunity is generally specific for epitopes that are remarkably conserved among different subtypes, suggesting that strategies to improve the cross-presentation of viral antigens by dendritic cells (DC) could elicit a broadly protective immune response. Previous studies have shown that limited proteolysis within the endocytic pathway can favorably influence antigen processing and thus immune responses. Herein, we demonstrate that chloroquine improves the cross-presentation of non-replicating influenza virus in vitro and T cell responses in mice following a single administration of inactivated HI-X31 virus. CD8+ T cells were also recruited to lymph nodes draining the site of infection and able to reduce viral load following pulmonary challenge with the heterologous PR8 virus. These findings may have implications for vaccination strategies aimed at improving the cross-presentation capacity of DCs and thus the size of effector and memory CD8+ T cells against influenza vaccines.
authors: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors: Bruno
authors: B
authors: Garulli
authors: Giuseppina
authors: G
authors: Di Mario
authors: Ester
authors: E
authors: Sciaraffia
authors: Daniele
authors: D
authors: Accapezzato
authors: Vincenzo
authors: V
authors: Barnaba
authors: Maria R
authors: MR
authors: Castrucci
mesh_terms: D000818:Animals; D002738:Chloroquine / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009975:Orthomyxoviridae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D007155:Immunologic Factors; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D002738:Chloroquine