Intranasal Vaccination with 1918 Influenza Virus-Like Particles Protects Mice and Ferrets from Lethal 1918 and H5N1 Influenza Virus Challenge

What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens?

“…immunizations of H1N1 influenza virus-like particles (VLPs) were protected against a lethal challenge with both the 1918 H1N1 virus and the heterotypic H5N1 virus (60). In addition, mucosal immunization was able to induce a higher level of cross-reactive IgG and IgA Abs compared with parenteral vaccination with the same vaccine (60). Mice immunized i.m.…”

“…Mucosal vaccination with H1N1 VLPs in ferrets also provided complete protection against lethal challenge with the H5N1 virus, whereas only 50% of ferrets survived infection after i.m. vaccination (60). Pulmonary immunization with extremely low doses (375-fold reduction in Ag dose) of influenza vaccine with the ISCOMATRIX adjuvant induced significantly higher titer serum Abs, and neutralizing anti-hemagglutinin Abs were only present in the lung after vaccination via the respiratory tract (61).…”

Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection

“…The titers of virus stocks were determined by plaque assay on MDCK cells, and stocks were maintained in Dulbecco's modified Eagle's medium (DMEM) (Gibco, Grand Island, NY) supplemented with 10% fetal calf serum (FCS) (HyClone, Logan, UT) and 1% penicillin/streptomycin (Gibco). The reconstructed 1918 and VN/1203 viruses were grown as previously described (33). All virus challenge experiments were performed under the guidance of the U.S. National Select Agent Program in negative-pressure HEPAfiltered biosafety level 3 enhanced (BSL-3ϩ) laboratories and with the use of a battery-powered Racal HEPA filter respirator (Racal Health and Safety Inc., Frederick, MD) according to Biomedical Microbiological and Biomedical Laboratory procedures (35).…”

Immunization with Biodegradable Nanoparticles Efficiently Induces Cellular Immunity and Protects against Influenza Virus Infection

“…Systemic delivery of vaccines induces a high titer of neutralizing Abs that prevent the disease but are not sufficient to prevent the infection at the mucosal entry site. Delivery strategies that mimic the natural process of infection by stimulating the innate and adaptive immune system with TLRs and viral Ags are currently under investigation (9)(10)(11). Nanoparticles (NPs) offer a new method for the design of vaccine systems.…”