Molecular Evaluation of Oral Immunogenicity of Hepatitis B Antigen Delivered by Hydrogel Microparticles

Xiang Yi Chen, Adeel Masood Butt, Mohd Cairul Iqbal Mohd Amin

Research output: Contribution to journalArticle

Abstract

The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4+ T lymphocytes and CD19+ B lymphocytes in splenocytes from mice orally vaccinated with antigen-loaded hydrogel MPs was comparable to that of the intramuscular vaccinated control, indicating early activation of lymphocytes elicited by our oral vaccine formulation in just two doses. These results demonstrated the potential of antigen-loaded hydrogel MPs as an oral vaccination method for hepatitis B.

Original languageEnglish
Pages (from-to)3853-3872
Number of pages20
JournalMolecular Pharmaceutics
Volume16
Issue number9
DOIs
Publication statusPublished - 3 Sep 2019

Fingerprint

Hepatitis B Antigens
Hydrogel
carbopol 940
Antigens
Vaccines
Mass Vaccination
Immunization Programs
Lymphocyte Activation
Hepatitis B
Pharmaceutical Preparations
Immunoglobulin A
Interleukin-2
Immunity
Permeability
Vaccination
B-Lymphocytes
Cytokines
T-Lymphocytes
Proteins

Keywords

  • bacterial nanocellulose
  • hepatitis B
  • hydrogel microparticles
  • oral vaccine carrier

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Molecular Evaluation of Oral Immunogenicity of Hepatitis B Antigen Delivered by Hydrogel Microparticles. / Chen, Xiang Yi; Butt, Adeel Masood; Mohd Amin, Mohd Cairul Iqbal.

In: Molecular Pharmaceutics, Vol. 16, No. 9, 03.09.2019, p. 3853-3872.

Research output: Contribution to journalArticle

@article{014a9fdc45db451994981ff8320c88ff,
title = "Molecular Evaluation of Oral Immunogenicity of Hepatitis B Antigen Delivered by Hydrogel Microparticles",
abstract = "The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4+ T lymphocytes and CD19+ B lymphocytes in splenocytes from mice orally vaccinated with antigen-loaded hydrogel MPs was comparable to that of the intramuscular vaccinated control, indicating early activation of lymphocytes elicited by our oral vaccine formulation in just two doses. These results demonstrated the potential of antigen-loaded hydrogel MPs as an oral vaccination method for hepatitis B.",
keywords = "bacterial nanocellulose, hepatitis B, hydrogel microparticles, oral vaccine carrier",
author = "Chen, {Xiang Yi} and Butt, {Adeel Masood} and {Mohd Amin}, {Mohd Cairul Iqbal}",
year = "2019",
month = "9",
day = "3",
doi = "10.1021/acs.molpharmaceut.9b00483",
language = "English",
volume = "16",
pages = "3853--3872",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "9",

}

TY - JOUR

T1 - Molecular Evaluation of Oral Immunogenicity of Hepatitis B Antigen Delivered by Hydrogel Microparticles

AU - Chen, Xiang Yi

AU - Butt, Adeel Masood

AU - Mohd Amin, Mohd Cairul Iqbal

PY - 2019/9/3

Y1 - 2019/9/3

N2 - The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4+ T lymphocytes and CD19+ B lymphocytes in splenocytes from mice orally vaccinated with antigen-loaded hydrogel MPs was comparable to that of the intramuscular vaccinated control, indicating early activation of lymphocytes elicited by our oral vaccine formulation in just two doses. These results demonstrated the potential of antigen-loaded hydrogel MPs as an oral vaccination method for hepatitis B.

AB - The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4+ T lymphocytes and CD19+ B lymphocytes in splenocytes from mice orally vaccinated with antigen-loaded hydrogel MPs was comparable to that of the intramuscular vaccinated control, indicating early activation of lymphocytes elicited by our oral vaccine formulation in just two doses. These results demonstrated the potential of antigen-loaded hydrogel MPs as an oral vaccination method for hepatitis B.

KW - bacterial nanocellulose

KW - hepatitis B

KW - hydrogel microparticles

KW - oral vaccine carrier

UR - http://www.scopus.com/inward/record.url?scp=85071783746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071783746&partnerID=8YFLogxK

U2 - 10.1021/acs.molpharmaceut.9b00483

DO - 10.1021/acs.molpharmaceut.9b00483

M3 - Article

C2 - 31398038

AN - SCOPUS:85071783746

VL - 16

SP - 3853

EP - 3872

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 9

ER -