Protection Against Influenza Virus Infection in Polymeric Ig Receptor Knockout Mice Immunized Intranasally with Adjuvant-Combined Vaccines

Abstract

The role of secretory IgA in conferring cross-protective immunity was examined in polymeric (p)IgR knockout (KO) mice immunized intranasally with different inactivated vaccines prepared from A/PR/8/34 (H1N1), A/Yamagata/120/86 (H1N1), A/Beijing/262/95 (H1N1), and B/Ibaraki/2/85 viruses and infected with the A/PR/8/34 virus in the upper respiratory tract (RT)-restricting volume. In wild-type mice, immunization with A/PR/8/34 or its variant (A/Yamagata/120/86 and A/Beijing/262/95) vaccines conferred complete protection or partial cross-protection against infection, while the B-type virus vaccine failed to provide protection. The protection or cross-protection was accompanied by an increase in the nasal A/PR/8/34 hemagglutinin-reactive IgA concentration, which was estimated to be >30 times the serum IgA concentration and much higher than the nasal IgG concentration. In contrast, the blockade of transepithelial transport of dimeric IgA in pIgR-KO mice reduced the degree of protection or cross-protection, in parallel with the marked increase in serum IgA concentration and the decrease in nasal IgA concentration (∼20 and 0.3 times those in wild-type mice, respectively). The degree of the reduction of protection or cross-protection was moderately reversed by the low but non-negligible level of nasal IgA, transudates from the accumulated serum IgA. These results, together with the absence of the IgA-dependent cross-protection in the lower RT and the unaltered level of nasal or serum IgG in wild-type and pIgR-KO mice, confirm that the actively secreted IgA plays an important role in cross-protection against variant virus infection in the upper RT, which cannot be substituted by serum IgG.

Two Doses of Parenterally Administered Split Influenza Virus Vaccine Elicited High Serum IgG Concentrations which Effectively Limited Viral Shedding upon Challenge in Mice

“…In contrast, S-IgA has been shown to be more cross-reactive with drifted strains [52] and an ideal influenza vaccine would also benefit from the induction of S-IgA.…”

Parenteral Nutrition Induces Organ Specific Alterations in Polymeric Immunoglobulin Receptor Levels

“…Densitometric measurements of protein bands were analyzed and quantified with the NIH Image J software. The anti-SC antibody used in this Western blot detected 2 bands at ∼120 kDa and ∼94 kDa representing pIgR and secretory component (SC), respectively [2,27]. The combined value of these two bands was determined for the quantitation of the pIgR protein expression in each case [1].…”

Sublingual vaccination with influenza virus protects mice against lethal viral infection

“…1B). Previous studies have shown that secretory IgA (SIgA) may play an important role in protecting against variant influenza virus infections in the upper respiratory tract (9). Thus, we used pIgR Ϫ/Ϫ mice in which the transepithelial transport of dimeric IgA is blocked to measure whether IgA Abs in the mucosal compartments induced by s.l.…”