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LW50020, a bacterial immunomodulator, is a preparation consisting of seven bacteria, commonly causing respiratory disease. When given orally, LW50020 has been shown to enhance the host defense of the respiratory tract. Intestinal lamina propria lymphocytes (LPL), Peyer's patch lymphocytes (PPL), and splenocytes from BALB/c mice gavaged either with LW50020 or carrier alone were isolated, labeled with either H33342, a supravital nuclear fluorochrome, or 51Cr, and injected i.v. into untreated, age-matched BALB/c mice. Two hours later, spleen, liver, lung, kidneys, Peyer's patch, and mesenteric lymph nodes of the recipients were harvested and screened for the presence of labeled cells. LPL from mice gavaged with carrier only (controls) migrated preferentially to the lung, PPL equally well to the lung, and the spleen and splenocytes were found mostly in the spleen. LPL and PPL from LW50020-treated mice were found in significantly larger numbers in the lungs of recipients than LPL and PPL from control animals. Both labeling techniques gave roughly the same results. Sixty-five per cent of LPL in the lung were Thy-1.2+ and 20% B cells. These findings should contribute to the understanding of parameters necessary for the assessment of the mode of action and efficacy of immunomodulation and vaccination via the mucosa-associated lymphoid tissue.

Encouraged by recent findings showing the usefulness of nonreplicating antigen delivery systems in the induction of mucosal immune responses, we investigated microspheres as a means to deliver LW 50020, an immunomodulator consisting of lysates of seven common respiratory pathogens. BALB/c mice were orally immunized with LW 50020 encapsulated into poly-(D,L-lactide-co-glycolide) (PLG) and poly-(L-lactic acid) (PLA) microspheres prepared by either a solvent-evaporation or a solvent-extraction double-emulsion technique. Particle uptake into intestinal Peyer’s patches, induction of antibodies in sera and secretion of immunoglobulins by isolated Peyer’s patches, lungs and spleen lymphocytes were investigated. Our results revealed size and surface characteristic-dependent uptake of microspheres into Peyer’s patches. Microsphere translocation into Peyer’s patches was efficient for 0.8-µm microspheres, but poor for 2.0-µm and surface-modified microspheres. We showed an enhanced immune response in the lungs and sera following oral immunization with 0.8-µm PLG solvent-evaporation microspheres. The immunomodulation was statistically significant as compared to free LW 50020. In contrast, oral immunization with other preparations caused reduced or absent modulation of the immune response compared to 0.8-µm microspheres and free antigen. These findings indicate that microspheres displaying small particle sizes, rapid antigen release and high antigen content provide optimal tools to deliver orally applied antigens.

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