Protection of mice against an influenza virus infection by oral vaccination with viral nucleoprotein incorporated into immunostimulating complexes

Abstract

Influenza A virus nucleoprotein (NP) was integrated into immunostimulating complexes (ISCOMs) after attachment of bacterial lipopolysaccharide to the antigen. Oral immunization with these NP-ISCOMs protected mice fully against an otherwise lethal challenge infection with an unrelated influenza virus subtype without the appearance of severe clinical signs or extensive pathological lesions in the lungs. Mice immunized with analogous bovine serum albumine-incorporated ISCOMs all died. After oral immunization, high titers of NP-specific antibodies, particularly IgA, could be detected in the bronchoalveolar fluid and in the blood serum. No cytotoxic lymphocytes could be demonstrated in the spleens or the lungs of vaccinated mice, and no anti-NP antibody-dependent cytolysis of infected host cells was mediated by complement or in the form of an antibody-dependent cell cytotoxicity. However, a vigorous delayed-type hypersensitivity reaction was produced after probing vaccinated animals with purified NP. No comparable protective immunity or antibody response was induced by a strictly intragastric administration of NP-ISCOMs. It appears, therefore, that the general and local immune response in the lungs was primarily stimulated through contact of NP-ISCOMs with the mucous membrane of the oro-pharyngeal cavity and that cytotoxic effects did not play a major role for the establishment of the protective immunity. Partial protection against a lethal challenge was observed in chickens immunized with NP-ISCOMs in the drinking water.

A Novel Role for Non-Neutralizing Antibodies against Nucleoprotein in Facilitating Resistance to Influenza Virus

“…Despite high titers of specific antibody generated by NP vaccination (9, 14, 17, 31, 35), the potential for these antibodies to facilitate influenza resistance has been underappreciated. In part, this disregard is due to early studies that failed to show protective effects of NP-specific antibodies in lymphopenic scid (4) and in BALB/c recipients (9).…”

Immune stimulating complexes as mucosal vaccines

“…Subsequent work has shown that the oral immunogenicity of ISCOMs is not confined to the model antigen OVA. Local and systemic immune responses which protected against challenge were seen after oral administration of ISCOMs containing subunit antigens derived from influenza virus, 50 , 51 surface sporozoite antigens from Eimeria falciformis 52 and somatostatin‐avidin 17 …”

Regulation of Antinucleoprotein IgG by Systemic Vaccination and Its Effect on Influenza Virus Clearance

“…NP vaccination accelerates viral clearance and prevents mortality in mice subsequently challenged with various influenza A virus strains (9,12,14,17,27,41,48,50,53,54,57). Thus, unlike inactivated virus vaccines, NP immunization provides cross-protection similar to that induced by prior influenza virus infection (heterosubtypic immunity [Het-I]) (12,14,17,27,53,54,57).…”