AAPS PharmSciTech

, Volume 19, Issue 3, pp 1168–1181 | Cite as

Lipid A adjuvanted Chylomicron Mimicking Solid Fat Nanoemulsions for Immunization Against Hepatitis B

Research Article

Abstract

Traditional parenteral recombinant hepatitis B virus (HBV) vaccines have effectively reduced the disease burden despite being able to induce seroprotective antibody titers in 5–10% vaccinated individuals (non-responders). Moreover, an estimated 340 million chronic HBV cases are in need of treatment. Development of safe, stable, and more effective hepatitis B vaccine formulation would address these challenges. Recombinant hepatitis B surface antigen (rHBsAg) entrapped solid fat nanoemulsions (SFNs) containing monophosphoryl lipid A (MPLA) that was prepared and optimized by quality by design (QbD) using response surface methodology (RSM), i.e., central composite design (CCD). Its immune potential was evaluated with preset immunization protocol in a murine model. Dose escalation study revealed that formulation containing 1 μg of rHBsAg entrapped SFNs with MPLA-induced significant higher humoral, and cellular response compared to the marketed vaccine (Genvac B) administered intramuscularly. SFNs with nanometric morphology and structural similarity with chylomicrons assist in improved uptake and processing to lymphatics. Moreover, the presence of an immunogenic component in its structure further augments delivery of rHBsAg to immune cells with induction of danger signals. This multi-adjuvant based approach explores new prospect for the dose sparing. Improved cellular immune response induced by this vaccine formulation suggests that it could be tested as an immunotherapeutic vaccine as well.

Key Words

quality by design dose sparing hepatitis B surface antigen solid fat nanoemulsions 

Notes

Acknowledgements

One of the authors Ms. Sunita Minz (SRF-RGNF) appreciates University Grants Commission, New Delhi, India for providing financial assistance. Authors are also grateful to Serum Institute of Pune, India for providing gift sample (rHBsAg). All India Institute of Medical Sciences (AIIMS, New Delhi, India) for providing electron microscopy facility and National Institute of Pharmaceutical Education and Research (NIPER, Mohali, India) for fluorescence spectroscopy and circular dichroism.

Compliance with Ethical Standards

The study was carried out as per guidelines issued by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA, Ministry of Social Empowerment and Justice, Government of India). The experimental protocol on animals was approved by the Institutional animal ethics committee (IAEC).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  1. 1.Department of PharmacyIndira Gandhi National Tribal UniversityAmarkantakIndia
  2. 2.SLT Institute of Pharmaceutical sciencesGuru Ghasidas VishwavidyalayaBilaspurIndia

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