Abstract

Many conventional vaccines are administered via a needle injection, while most pathogens primarily invade the host via mucosal surfaces. Moreover, protective IgA antibodies are insufficiently induced by parenteral vaccines. Mucosal immunity induces both local and systemic response to pathogens and typically lasts for long periods of time. Therefore, vaccination via mucosal routes has been increasingly explored. However, mucosal vaccines require potent adjuvants to become efficacious. Despite many efforts to develop safe and robust adjuvants for mucosal vaccines, only a few have been approved for use in human formulations. The aim of our study was to design, develop and characterize new silicone oil-based nanoadjuvant candidates for intranasal vaccines with potential to become mucosal adjuvants. We have developed an array of nanoadjuvant candidates (NACs), based on well-defined ingredients. NAC1, 2 and 3 are based on silicone oil, but differ in the used detergents and organic solvents, which results in variations in their droplet size and zeta potential. NACs’ cytotoxicity, Tumor Necrosis Factor α (TNF-α) induction and their effect on antigen engulfment by immune cells were tested in vitro. Adjuvant properties of NACs were verified by intranasal vaccination of mice together with ovalbumin (OVA). NACs show remarkable stability and do not require any special storage conditions. They exhibit bio-adhesiveness and influence the degree of model protein engulfment by epithelial cells. Moreover, they induce high specific anti-OVA IgG antibody titers after two intranasal administrations. Nanoadjuvant candidates composed of silicone oil and cationic detergents are stable, exhibit remarkable adjuvant properties and can be used as adjuvants for intranasal immunization.

Highlights

  • Adjuvants are vaccine components that are designed to enhance the development of prolonged humoral and/or cell-mediated immune response to the target antigen

  • Preliminary studies of formulations based on silicone oil and a mixture of cationic and non-ionic detergents have allowed the formation of a series of nanoadjuvant candidates (NACs)

  • We focused on droplet size and Zeta potential (ZP) as these parameters are crucial for biological interactions like bioadhesion and particle engulfment by immune cells [32,33,34]

Read more

Summary

Introduction

Adjuvants are vaccine components that are designed to enhance the development of prolonged humoral and/or cell-mediated immune response to the target antigen. Effective adjuvant should possess at least one of the following features: to “depot” antigen, facilitate antigen presentation and antigen sampling by mucosal dendritic cells, activate/modulate the immune response, and induce the cytotoxic T lymphocytes [1]. Food and Drug Administration for use in the human vaccine: Alum, AS01B, MF59TM, virosome, AS03, ASO4 and CpG 1018 [2,3]. They are used parenterally in influenza vaccines. That is widely used for parenteral immunizations, is unfit for mucosal vaccines since it does not induce mucosal immunity

Objectives
Methods
Results
Discussion
Conclusion

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 call

Disclaimer: 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.