An experimental influenza subunit vaccine (iscom): induction of protective immunity to challenge infection in mice after intranasal or subcutaneous administration

Abstract

SUMMARYAn experimental influenza virus {A/PR/8/34{HINI)) vaccine was icstcd and evaluated in mice. The mice were inoculated once or twice intranasally or Bubcutancously with I or lO/igofiscoms prior to ehallenge with high doses oflive virus. It was demonstrated that two intranasal administrations were as efficient as two s.e. administrations, both routes inducing high levels of aniibody and protection against challenge infection. With a one-dose regimen, the s.e. route induced a somewhat higher antibody response than ihe inlranasal route; this might be explained by technical difficulties connected with an inlranasal administration.

Lipid-Based Particles: Versatile Delivery Systems for Mucosal Vaccination against Infection

“…Several studies have reported potent induction of mucosal immune responses, including robust IgA production in nasal washes and the lung, after nasal/pulmonary vaccination with ISCOMs harboring antigenic entities from Influenza virus ( 191 – 194 ), respiratory syncitial virus ( 195 ), Hepatitis B virus ( 196 ) and measles ( 197 ). Protective efficacy was observed as well after vaccination with an Influenza subunit vaccine composed of ISCOMs ( 198 ), adjuvanted ISCOM-based anti- M. tuberculosis and anti-Influenza vaccines ( 199 , 200 ) and Helicobacter pylori -Ags delivered via ISCOMs ( 201 ). In some cases, such immunization proved more efficient than parenteral injection ( 196 , 202 ).…”

Mouse models for the study of mucosal vaccination against otitis media

“…Influenza vaccines tested in murine models include live topical vaccines, inactivated vaccines, and subunit vaccines consisting of antigens from pathogenic organisms, including the major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA) [47,[156][157][158][159][160][161][162][163][164]. In addition, a number of influenza DNA vaccine candidates are in various stages of development, with the hope that this vaccine approach induces a broad spectrum of immunity against multiple strains of influenza virus.…”

“…OM, mucosal vaccines have been shown to provide effective protection against influenza virus, RSV and PIV in the respiratory tract (Table 5). Vaccine-induced protection against viral infections is likely to be associated with both humoral (S-IgA, serum IgG antibodies) and cellmediated (CTLs) immunity [157,135,184]. Renegar et al [185] demonstrated that S-IgA prevents influenza virus-induced pathology in the upper respiratory tract but serum IgG antibody failed to prevent viral infection of the nose although it did neutralize newly replicated virus after infection had been initiated.…”

“…A variety of mucosal antigen delivery systems have been developed to increase uptake of antigen at mucosal surfaces, including biodegradable nanoparticles [160] and biopolymers such as chitosan [134], liposomes [158,159,132], and ISCOMs [156,157,166,169]. Studies with recombinant bacterial [115,206] and viral [191] vector systems have demonstrated the feasibility of creating live delivery systems that express recombinant DNA encoding foreign antigens but without the ability to allow reversion to a virulent phenotype [115,206].…”

“…Studies with recombinant bacterial [115,206] and viral [191] vector systems have demonstrated the feasibility of creating live delivery systems that express recombinant DNA encoding foreign antigens but without the ability to allow reversion to a virulent phenotype [115,206]. ISCOMs have shown the potential to induce a full range of humoral and CTL responses, both of which appear to be important for antiviral protection [156,157,166,169]. Other strategies include the incorporation of antigens into various microparticles [134,160] or membrane-bound vesicles [158,133,159], procedures that promote antigen uptake and provide protection against proteolytic digestion.…”