Modified Pulmonary Surfactant Is a Potent Adjuvant That Stimulates the Mucosal IgA Production in Response to the Influenza Virus Antigen

Abstract

The intranasal administration of influenza hemagglutinin (HA) vaccine with Surfacten, a modified pulmonary surfactant free of antigenic c-type lectins, as a mucosal adjuvant induced the highest protective mucosal immunity in the airway. The intranasal immunization of mice with HA vaccine (0.2 μg)-Surfacten (0.2 μg) selectively induced the neutralizing anti-HA IgA, but not IgG, and conferred nearly maximal protection in the airway, without inducing a systemic response. In contrast, intranasal inoculation of vaccine with 0.2 μg of the potent mucosal adjuvant cholera toxin B* (CT-B*), prepared by adding 0.2% native CT to the B subunit of CT, induced both anti-HA IgA and IgG in the airway and in the serum. The intranasal administration of HA vaccine alone induced a limited amount of mucosal IgA against influenza virus. Although the s.c. administration of HA vaccine prominently induced serum IgG and IgA, Surfacten and CT-B* did not enhance their induction, and the concentrations of Abs leaking into the airways were insufficient to prevent viral multiplication. The intranasal administration of HA-Surfacten stimulated the expression of MHC class II, CD40, and CD86 molecules in the CD11c-positive cells isolated from the nasal mucosa, but not the expression of cells from the lungs or spleens. Lymphocytes isolated from the airway mucosa after intranasal HA-Surfacten immunization prominently induced TGF-β1 which, compared with inoculation without Surfacten, promoted an Ag-specific mucosal IgA response. Surfacten alone, however, did not induce TGF-β1. Our observations suggest that Surfacten, by mimicking the natural surfactant, is an effective mucosal adjuvant in the process of airway immunization.

Selection of Adjuvants for Enhanced Vaccine Potency

“…DDA was found equally effective as Adju-Phos when used with BBG2Na for protection against viral challenge in mice and rats [395,396]. Intranasal administration of influenza hemagglutinin (HA) vaccine with Surfacten, a modified pulmonary surfactant, induced higher protective mucosal immunity in the airway without inducing a systemic response in mice [283].…”

“…Options to bypass their toxicities include use of subunits of toxins, toxoids, or structurally modified versions [281]. The toxin subunits could be still effective [282,283] but a less adjuvantation effect would be expected relative to the complete toxin [284]. Several non-toxic LT mutants have been recently reviewed [285].…”

Oral Clarithromycin Enhances Airway Immunoglobulin A (IgA) Immunity through Induction of IgA Class Switching Recombination and B-Cell-Activating Factor of the Tumor Necrosis Factor Family Molecule on Mucosal Dendritic Cells in Mice Infected with Influenza A Virus

“…At days 8 and 12 after infection, nasal washes (NWs), bronchoalveolar fluids (BALF), and plasma were collected as described previously (27,45) and subjected to enzyme-linked immunosorbent assay (ELISA) to determine anti IAV-specific S-IgA and IgG levels (27,33,39). Mononuclear cells isolated from the MeLNs, lungs, NPs, and spleen were subjected to an enzyme-linked immunosorbent spot (ELISPOT) assay to determine the numbers of IgA and IgG antibody (Ab)-forming cells (AFCs), as described previously (15,17,39).…”

Intranasal Immunization with a Formalin-Inactivated Human Influenza A Virus Whole-Virion Vaccine Alone and Intranasal Immunization with a Split-Virion Vaccine with Mucosal Adjuvants Show Similar Levels of Cross-Protection

“…However, the toxin causes severe diarrhea and nasal discharge, so a safer and more effective adjuvant is needed for intranasal influenza virus vaccines in clinical use. Recent studies have demonstrated that synthetic double-stranded RNA polyriboinosinic acid-polyribocytidylic acid [poly(I·C)], modified pulmonary surfactant, and poly(␥-glutamic acid) nanoparticles (␥-PGA-NPs) are safe and potent candidates for use as an adjuvant in mucosal influenza virus vaccines (8,13,14). These materials induce dendritic cell (DC) activation, which plays an important role in mucosal adjuvant activity.…”