Active synthesis of hemagglutinin-specific immunoglobulin A by lung cells of mice that were immunized intragastrically with inactivated influenza virus vaccine

Abstract

Intragastric inoculation with whole-virion vaccine of inactivated influenza virus resulted in production of hemagglutinin (HA)-specific immunoglobulin A (IgA) and IgG both in lung lavage fluids and in serum samples of mice. HA-specific IgA was the predominant isotypic antibody secreted in the lung lavage fluids (average IgA/IgG ratio, 13:1), whereas HA-specific IgG was the major antibody class in serum (average IgA/IgG ratio, 0.3:1). These responses were similar to the antibody responses stimulated by intranasal infection with live influenza virus. In vitro cultures of lymphoid cells from lungs and Peyer's patches, but not from spleens, in the presence of homologous antigen, from mice vaccinated intragastrically synthesized mostly HA-specific IgA. Mice immunized parenterally with inactivated influenza virus produced only IgG in lung lavage fluids and sera. Cultures of lymphoid cells from their spleens, but not their lungs, synthesized HA-specific IgG upon antigenic stimulation in vitro; neither synthesized IgA. These in vitro cell culture results, as well as the inverse relationship of IgA/IgG ratios in lung lavage fluids and sera, demonstrated that the IgA antibody in lung lavage fluids was actively synthesized locally in the lungs of intragastrically immunized mice. This finding was consistent with the migratory distribution of antigen-primed lymphoid cells from Peyer's patches to distant lymphoid tissue such as lung. Intragastric vaccination conferred protection against intranasal challenge with a lethal dose of virulent virus.

A novel particulate influenza vaccine induces long-term and broad-based immunity in mice after oral immunization

“…Liew and coworkers (14) have reported, using radioimmunoassay, the presence of cross-reactive IgA against whole-virus antigen in the lung washings, which correlated with protection between heterotypic challenge. Our study shows that the presence of virus-specific cross-reactive IgA antibodies in the nasal washings supports a role for this antibody within the upper respiratory tract, which is consistent with previous studies (3,7). Although the level of IgA antibodies does not corre-late with protection as well as IgG antibodies did, this appears likely due to the concentrations of virus present in the nasal washings, which interferes with the ELISA or the induction of high dose tolerance.…”

Protection against Influenza Virus Infection of Mice Fed Bifidobacterium breve YIT4064

“…The various dilutions of the allantoic fluid were used for oral immunization and nasal infection. Oral immunization with various concentrations of live PR8 via a stomach tube was performed in mice that had been pretreated with an intramuscular injection of cimetidine (Tagamet; Smith Kline & French Laboratories, Philadelphia, Pa.) (1.2 mg per mouse) 1 h before (2) and with 3% NaHCO 3 via a stomach tube just before the oral immunization. Nasal infection was performed by dropping 10 or 1 l of fluid containing various concentrations of PR8 into each nostril (injection with 20 or 2 l per mouse) after the mice were anesthetized by an intraperitoneal injection of sodium amobarbital (0.25 g per mouse).…”

The Regulation of Pulmonary Immunity

“…(Ckdenas and Clements, 1992). Ample evidence has documented that IgA precursors generated in the gut home to bronchial mucosa (Weisz-Carrington et al, 1987;Chen et al, 1987;Rued1 et al, 1994), although the converse does not appear to occur to an appreciable extent (McDermott and Bienenstock, 1979;Joel and Chanana, 1987;VanCott et d . , 1994).…”