Development of Soluble Inulin Microparticles as a Potent and Safe Vaccine Adjuvant and Delivery System

被引:23
作者
Kumar, Sunny [1 ]
Tummala, Hemachand [1 ]
机构
[1] S Dakota State Univ, Coll Pharm, Brookings, SD 57006 USA
关键词
vaccine; vaccine adjuvant; vaccine delivery; polymers; soluble inulin; ovalbumin; microparticles; DENDRITIC CELLS; PLGA NANOPARTICLES; IMMUNE-RESPONSES; STABILIZATION; FORMULATIONS; IMMUNIZATION; INDUCTION; MOLECULES; INFECTION; PROTEINS;
D O I
10.1021/mp3006374
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The goal of the present study is to develop a potent and safe vaccine adjuvant that can also stabilize vaccine formulations during lyophilization and storage. Inulin is a safe plant polysaccharide, and in its water soluble isoform, it is known to stabilize protein formulations during storage. However, soluble inulins have never been shown to stimulate the immune system. In this study, for the first time, we showed that water soluble inulins could be developed into vaccine adjuvants by formulating as antigen encapsulated microparticles. A method was developed to prepare soluble inulin microparticles (sIMs) with high encapsulation efficiency (similar to 75%) and loading (similar to 75 mu g/mg) of the antigen. When immunized in mice, sIMs have generated robust Th2-type antibody titers (IgG1: 500,000) compared to unadjuvanted antigens (IgG1: 17,500) or alum adjuvanted antigens (IgG1: 80,000). In vitro assays showed that a higher proportion of antigen presenting cells (APC's) have taken up the antigen when presented in sIMs versus in solution (99 % vs 22 %). In addition, the amount of antigen taken up per cell has also been enhanced by more than 25 times when antigen was presented in sIMs. Efficient uptake of the antigen by APCs through sIMS was attributed to the observed enhancement in the immune response by antigen loaded sIMs. The sIMs neither caused any granuloma/tissue damage at the injection site in mice nor were they toxic to the APC's in cell culture. In conclusion, the current study has developed a safe, soluble inulin based vaccine adjuvant and delivery system.
引用
收藏
页码:1845 / 1853
页数:9
相关论文
共 37 条
[1]   Vaccine adjuvants revisited [J].
Aguilar, J. C. ;
Rodriguez, E. G. .
VACCINE, 2007, 25 (19) :3752-3762
[2]   Comparison of numerous delivery systems for the induction of cytoxic T lymphocytes by immunization [J].
Allsopp, CEM ;
Plebanski, M ;
Gilbert, S ;
Sinden, RE ;
Harris, S ;
Frankel, G ;
Dougan, G ;
Hioe, C ;
Nixon, D ;
Paoletti, E ;
Layton, G ;
Hill, AVS .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (08) :1951-1959
[3]   ADJUVANTS - CURRENT STATUS, CLINICAL PERSPECTIVES AND FUTURE-PROSPECTS (REPRINTED FROM TRENDS IN PHARMACOLOGICAL SCIENCES, VOL 14, PG 174-178, 1993) [J].
AUDIBERT, FM ;
LISE, LD .
IMMUNOLOGY TODAY, 1993, 14 (06) :281-284
[4]   Development of a dried influenza whole inactivated virus vaccine for pulmonary immunization [J].
Audouy, Sandrine A. L. ;
van der Schaaf, Gieta ;
Hinrichs, Wouter L. J. ;
Frijlink, Henderik W. ;
Wilschut, Jan ;
Huckriede, Anke .
VACCINE, 2011, 29 (26) :4345-4352
[5]   PLGA nanoparticles in drug delivery: The state of the art [J].
Bala, I ;
Hariharan, S ;
Kumar, MNVR .
CRITICAL REVIEWS IN THERAPEUTIC DRUG CARRIER SYSTEMS, 2004, 21 (05) :387-422
[6]  
Barclay T., 2010, Journal of Excipients and Food Chemicals, V1, P27
[7]   Plant glycans: friend or foe in vaccine development? [J].
Bosch, Dirk ;
Schots, Arjen .
EXPERT REVIEW OF VACCINES, 2010, 9 (08) :835-842
[8]   VIROLOGICAL AND IMMUNOLOGICAL CHARACTERIZATION OF LONG-TERM SURVIVORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION [J].
CAO, YZ ;
QIN, LM ;
ZHANG, LQ ;
SAFRIT, J ;
HO, DD .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (04) :201-208
[9]   Rational design of stable lyophilized protein formulations: Some practical advice [J].
Carpenter, JF ;
Pikal, MJ ;
Chang, BS ;
Randolph, TW .
PHARMACEUTICAL RESEARCH, 1997, 14 (08) :969-975
[10]   A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles [J].
Cohen-Sela, Einat ;
Chorny, Michael ;
Koroukhov, Nickolay ;
Danenberg, Haim D. ;
Golomb, Gershon .
JOURNAL OF CONTROLLED RELEASE, 2009, 133 (02) :90-95