Induction of Heterosubtypic Immunity to Influenza Virus by Intranasal Immunization

Abstract

Recovery from live influenza virus infection is known to induce heterosubtypic immunity. In contrast, immunity induced by inactivated vaccines is predominantly subtype specific. In this study, we investigated the heterosubtypic protective immunity induced by inactivated influenza virus. Intranasal immunization of mice with inactivated influenza virus A/PR8 (H1N1) provided complete protection against the homologous virus and a drift virus within the same subtype, A/WSN (H1N1), but not against the heterosubtypic virus A/Philippines (H3N2). However, coadministration of inactivated virus with cholera toxin as an adjuvant conferred complete heterosubtypic protection, without observed illness, even under conditions of CD4+ or CD8+ T-cell depletion. Analysis of immune correlates prior to challenge and postchallenge indicated that humoral immune responses with cross-neutralizing activity in lungs and in sera play a major role in conferring protective immunity against heterosubtypic challenge. This study has significant implications for developing broadly cross-reactive vaccines against newly emerging pathogenic influenza viruses.

Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine

“…Influenza VLP vaccines can increase the speed of vaccine production in part because they are manufactured using cell culture instead of the cumbersome egg-based manufacturing methods in use today for inactivated virus-based vaccines (39). In this study, we propose that influenza VLP vaccination can be further expedited by administration using a microneedle patch applied to the skin.…”

Cytotoxic T Cells Are the Predominant Players Providing Cross-Protective Immunity Induced by γ-Irradiated Influenza A Viruses

“…Despite these observations, the immunological basis of heterosubtypic immunity against influenza A virus infection and the contribution of the Tc-cell response remain important areas of research. Importantly, in order to investigate the underlying mechanism for heterosubtypic immunity, many researchers have used low doses of live viruses to prime animals prior to heterosubtypic challenge (8,16,28,38,41,55). It has been reported that in vivo depletion of CD4 ϩ or CD8 ϩ T cells (8,14,28,30,41) or of both T-cell subsets (14) had only a minor effect on heterosubtypic protection.…”

Protective Effect of Korean Red Ginseng Extract on the Infections by H1N1 and H3N2 Influenza Viruses in Mice

“…A/PR/8/34 virus grown in egg allantoic fluids was purified using sucrose-gradient ultracentrifugation and inactivated using formalin (0.1%) as described. 30 Korean red ginseng extract (ginseng extract), a concentrated form of the commercial ginseng product for human use, was kindly provided by Korea Ginseng Corp. (Daejeon, Korea). In brief, fresh roots of P. ginseng that had grown for 6 years were washed, steamed at 100°C for 2-3 h, and dried.…”

“…30 In brief, lungs were collected at Day 4 postinfection with A/California/4/2009 virus or a mixture of A/California/4/2009 virus and ginseng extract. Serially diluted lung extracts were added to six-well plates containing confluent MDCK cell monolayers and incubated at 37°C for 1 h. Overlay medium containing DEAE dextran, nonessential amino acids, glutamine, and trypsin was added and incubated for 2 or 3 days.…”

“…Influenza viruses were grown in 11-day-old embryonated hens' eggs and harvested as described. 30 Egg allantoic fluids were harvested and stored at -80°C until use. Madin-Darby canine kidney (MDCK) cells purchased from the American Type Culture Collection (Manassas, VA, USA) were maintained in Dulbecco's modified Eagle's medium and used to determine virus titers from egg allantoic fluids and mouse lung homogenates by a plaque assay.…”