Adjuvant Activity of the Heat-Labile Enterotoxin from Enterotoxigenic Escherichia coli for Oral Administration of Inactivated Influenza Virus Vaccine

Abstract

Alternative strategies for vaccination against influenza that elicit both systemic antibody and mucosal IgA responses are needed to improve the efficacy in protection against infection. This study demonstrated that oral delivery of inactivated influenza vaccine with the heat-labile enterotoxin (LT) from enterotoxigenic Escherichia coli elicited the spectrum of humoral and cell-mediated responses in BALB/c mice critical for the protection and recovery from influenza virus infection. Coadministration of LT with oral influenza vaccine increased antiviral serum IgG and mucosal IgA responses compared with administration of oral influenza vaccine alone. Serum hemagglutination-inhibition and neutralizing antibodies were also augmented by LT. The adjuvant potentiated protection from infection with influenza A H3N2 viruses in mouse lower and upper respiratory tracts, enabling the use of lower doses of oral vaccine. Coadministration of LT with oral inactivated influenza vaccine induced influenza virus-specific proliferative T cells, interleukin-2 production, and major histocompatibility complex class I-restricted cytotoxic T cells.

Impact of Prior Seasonal H3N2 Influenza Vaccination or Infection on Protection and Transmission of Emerging Variants of Influenza A(H3N2)v Virus in Ferrets

“…Both upper respiratory tract (URT; sampled by tracheal/nasal wash) and lower respiratory tract (LRT; bronchoaveolar [lung] wash samples) were collected 5 weeks after prior infection or final vaccination using a novel protocol adapted from protocols established for mice (24). Ferrets were exsanguinated by cardiac puncture under ketamine anesthesia to best avoid blood contamination of the mucosal samples.…”

Protection of Mice and Poultry from Lethal H5N1 Avian Influenza Virus through Adenovirus-Based Immunization

“…The HI assay was performed using four HA units of virus and 1% horse red blood cells as described previously (32). H5N1 influenza virus-specific immunoglobulin G (IgG) antibodies were detected by enzyme-linked immunosorbent assay (ELISA) as previously described (20), except that 1 g/ml of purified baculovirus-expressed recombinant H5 HA protein from VN/1203/04 virus (Protein Sciences Corporation, Meriden, CT) was used to coat plates. ELISA end point titers were expressed as the highest dilution that yielded an optical density greater than twice the mean plus one standard deviation of that of similarly diluted negative control samples.…”

Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets Viral Attachment to Cells

“…HA binding assays were performed as previously described with slight modifications (15,19). Briefly, microtiter wells were coated with increasing concentrations of peptide (0 to 75 M) and washed with PBS containing 0.1% Tween-20, and nonspecific binding sites were blocked with 2% Fraction V BSA (Fisher Scientific) in PBS-0.1% Tween-20.…”