Immunoglobulin-A antibodies in upper airway secretions may inhibit intranasal influenza virus replication in mice but not protect against clinical illness

Mice immunized intranasally with a formalin-inactivated A/PR/8/34 (H1N1) influenza whole virus vaccine adjuvanted with cholera toxin, outer membrane vesicles from group B meningococci or formalin-inactivated whole cell Bordetella pertussis were protected against replication of the homologous virus in the nasal cavity. Only some mice were protected against clinical illness measured as weight loss and lowered body temperature. All mice immunized subcutaneously with one-tenth the intranasal vaccine dose without adjuvant were protected against clinical illness but not against local mucosal viral replication. Replicating virus was primarily found in animals with low concentrations of immunoglobulin (Ig)-A antibodies in saliva regardless of concentrations of IgG antibodies in serum. Clinical illness was seen only in those with low serum antibodies regardless of antibody levels in saliva. Nonreplicating nasal vaccines may not be sufficiently protective unless they also have a substantial influence on systemic immunity.