Abstract
Murabutide (MB) is a synthetic immunomodulator recognized by the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptor on mammalian cells. MB has previously been approved for testing in multiple human clinical trials to determine its value as an antiviral therapeutic, and as an adjuvant for injected vaccines. We have found a new use for this immunomodulator; it functions as a mucosal adjuvant that enhances immunogenicity of virus-like particles (VLP) administered intranasally. MB enhanced Norwalk virus (NV) VLP-specific IgG systemically and IgA production at distal mucosal sites following intranasal (IN) vaccination. A dose escalation study identified 100 µg as the optimal MB dosage in mice, based on the magnitude of VLP-specific IgG, IgG1, IgG2a and IgA production in serum and VLP-specific IgA production at distal mucosal sites. IN vaccination using VLP with MB was compared to IN delivery VLP with cholera toxin (CT) or gardiquimod (GARD) and to parenteral VLP delivery with alum; the MB groups were equivalent to CT and GARD and superior to alum in inducing mucosal immune responses and stimulated equivalent systemic VLP-specific antibodies. These data support the further testing of MB as a potent mucosal adjuvant for inducing robust and durable antibody responses to non-replicating subunit vaccines.
Highlights
IntroductionThe majority of US FDA approved vaccines are administered parenterally (subcutaneous or intramuscular routes) and induce systemic immune responses (measured by serum antibody production)
The majority of US FDA approved vaccines are administered parenterally and induce systemic immune responses
Serum IgG1 titers following boosting increased by 23, 14, and 23-fold for the virus-like particles (VLP) codelivered with MB (25 mg, 100 mg, and 250 mg) groups, respectively, while titers following boosting increased by 44- fold for the VLP and alum group, and 25-fold for the VLP alone group, and all levels remained consistently elevated throughout the duration of the study (Fig. 1C)
Summary
The majority of US FDA approved vaccines are administered parenterally (subcutaneous or intramuscular routes) and induce systemic immune responses (measured by serum antibody production). This systemic IgG may participate in local immune responses at distal mucosal sites, with reduced efficacy relative to secretory IgA (sIgA). Since many pathogens gain entry through mucosal sites, efforts have been made to induce robust sIgA throughout the common mucosal immune system (CMIS) by mucosal vaccination The development of these mucosal vaccines has been limited by the lack of mucosal adjuvants that are both safe and potent inducers of mucosal and systemic immune responses. Adjuvants containing alum, in the form of crystalline aluminum oxyhydroxide, amorphous aluminum hydroxyl-phosphate, or a formulation of anhydrous aluminum hydroxycarbonate (ImjectH alum) differ from each other in the exact mechanisms that result in systemic immune responses to the target antigen [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
