Evaluation of ISCOM vaccines for mucosal immunization against hepatitis B

Abstract

Immune stimulating complexes (ISCOMs) incorporating recombinant hepatitis B surface antigen (HBsAg) was prepared for induction of humoral, cellular and mucosal immunity by intranasal administration. Prepared ISCOMs were characterized for its size, shape, incorporation efficiency, zeta potential, and antigen integrity. Designed ISCOMs possessed negative zeta potential (−21.7 mV) and an average size of 44.1 nm with antigen incorporation efficiency ∼ 39 %. Serum anti-HBsAg IgG titer after three high nasal doses of ISCOMs was comparable with titer recorded after alum-HBsAg administered subcutaneously. Similarly, modest but higher cellular response (cytokines level in spleen homogenates) and significantly higher secretory sIgA response in mucosal secretions was observed (P < 0.001) in case of HBsAg ISCOM vaccines. Whereas, alum-HBsAg vaccine did not elicit considerable cellular or mucosal response. Thus, ISCOMs produced humoral, mucosal, and cellular immune responses upon nasal administration although high and multidose administrations were required to elicit potent immune responses. These data demonstrate potential of ISCOMs in their use as a carrier adjuvant for nasal subunit vaccines against hepatitis B.

Keywords::

• Hepatitis B virus
• immune response
• nasal vaccine delivery
• Quil A
• ISCOMs

Acknowledgements

Authors are thankful to Shantha Biotechnics Ltd. (Hyderabad, India), Branntag Biosector Denmark and Lipoid GmBH, Germany for providing gift samples of recombinant HBsAg Quil A and lipids respectively. Authors are also thankful to All India Institute of Medical Sciences (AIIMS, New Delhi, India) and Prof (Dr.) S. C. Lakhotia, Cytogenetics research laboratory, Banaras Hindu University, Varanasi, India for providing Electron Microscopy and CLSM facility, respectively.

Declaration of interest: The authors report no conflicts of interests.