Multistrain influenza protection induced by a nanoparticulate mucosal immunotherapeutic.
All commercial influenza vaccines elicit antibody responses that protect against seasonal infection, but this approach is limited by the need for annual vaccine reformulation that precludes efficient responses against epidemic and pandemic disease. In this study we describe a novel vaccination approach in which a nanoparticulate, liposome-based agent containing short, highly conserved influenza-derived peptides is delivered to the respiratory tract to elicit potent innate and selective T cell-based adaptive immune responses. Prepared without virus-specific peptides, mucosal immunostimulatory therapeutic (MIT) provided robust, but short-lived, protection against multiple, highly lethal strains of influenza in mice of diverse genetic backgrounds. MIT prepared with three highly conserved epitopes that elicited virus-specific memory T-cell responses but not neutralizing antibodies, termed MITpep, provided equivalent, but more durable, protection relative to MIT. Alveolar macrophages were more important than dendritic cells in determining the protective efficacy of MIT, which induced both canonical and non-canonical antiviral immune pathways. Through activation of airway mucosal innate and highly specific T-cell responses, MIT and MITpep represent novel approaches to antiviral protection that offer the possibility of universal protection against epidemic and pandemic influenza.
Tai
W
W
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Roberts
L
L
Seryshev
A
A
Gubatan
J M
JM
Bland
C S
CS
Zabriskie
R
R
Kulkarni
S
S
Soong
L
L
Mbawuike
I
I
Gilbert
B
B
Kheradmand
F
F
Corry
D B
DB
D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D018928:Immunity, Mucosal / Q000276:immunology; D007156:Immunologic Memory; D007167:Immunotherapy; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D053758:Nanoparticles; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D020545:Respiratory Mucosa / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D007252:Influenza Vaccines; D022223:Vaccines, Subunit