The immunostimulating complex (ISCOM) is an efficient mucosal delivery system for respiratory syncytial virus (RSV) envelope antigens inducing high local and systemic antibody responses

Abstract

SUMMARYISCOM is an efficient mucosal delivery system for RSV envelope proteins as measured by antibody responses in respiratory tract secretions and in sera of mice following two intranasal (i.n.) administrations. Intranasally administered RSV ISCOMs induced high levels of IgA antibodies both in the upper respiratory tract and in the lungs. In the lungs, a prominent and long-lasting IgA response was recorded, which still persisted 22 weeks after the second i.n. immunization when the experiment ended. Subcutaneous (s.c.) immunization only induced low IgA titres in the upper respiratory tract and no measurable response to RSV was found in the lungs. Differences were also noticed in serum between the i.n. and s.c. modes of immunization. ISCOMs given intranasally induced earlier, higher and longer lasting IgM and IgG1 serum anti-RSV antibody responses than those induced by the s.c. mode of administration. A low serum IgE response was only detectable at 2 weeks after i.n. immunization with ISCOMs and after s.c. immunization with an inactivated virus, but no IgE response was detectable after s.c. injection of ISCOMs. The serum IgA response was more pronounced following s.c. injection of inactivated virus than after i.n. application of ISCOMs, and a clear-cut booster effect was obtained with a second immunization. Virtually no serum IgA response was detected after the s.c. administration of ISCOMs. In conclusion, the high immune responses induced by RSV ISCOMs in the respiratory tract and serum after i.n. administration indicate prominent mucosal delivery and adjuvant properties of the ISCOMs, warranting further studies.

Recurrent Respiratory Syncytial Virus Infections in Allergen-Sensitized Mice Lead to Persistent Airway Inflammation and Hyperresponsiveness

“…This suggests that the enhanced IgE response observed in ASRSV mice is probably due to the increase in IgE Abs specific to RSV. This inference is consistent with previous reports that RSV is capable of inducing an IgE class switch (31,32). The RSV G protein especially mounts an IgE response (33,34).…”

Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge

“…Conversely, a third study using G peptides and CT reported complete lung protection associated with serum IgG levels comparable to those evoked by live RSV infection, but failed to demonstrate secretory IgA [26]. Use of iRSV encapsulated in immunostimulating complexes (ISCOM) has also been documented and evokes strong mucosal and systemic humoral responses, although a clear comparison with immunity following live RSV immunisation is still lacking [27,28]. Finally, studies using intranasally delivered MHC class I peptides have allowed the development of protective RSV-specific CTL, but those appeared to be either short-lived [29] or linked with enhanced disease upon RSV challenge [30].…”

Mucosal delivery of vaccines in domestic animals

“…Intranasal immunization with respiratory syncytial virus (RSV) antigens in ISCOM induced high levels of IgA in the upper respiratory tract and in the lungs of mice [70]. Antigens from Mycoplasma mycoides subspecies mycoides, a cause of severe lung disease in cattle, were incorporated in ISCOM and induced mucosal and systemic IgG1, IgG2a and IgG2b antibody responses in mice [1].…”