Single dose, polymeric, microparticle based vaccines: The influence of formulation conditions on the magnitude and duration of the immune response to a protein antigen

被引:75
作者
Coombes, AGA
Lavelle, EC
Jenkins, PG
Davis, SS
机构
[1] Dept. of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, University Park
[2] Proteus Molecular Design, Macclesfield, Lyme Green Business Park
基金
英国惠康基金;
关键词
D O I
10.1016/S0264-410X(96)00077-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ovalbumin-loaded poly(D,L-lactide co-glycolide) [OVA-loaded PLG] microparticles, produced by emulsion/solvent evaporation stimulated the production of high serum IgG antibody levels after a single subcutaneous (s.c.) administration in mice and the duration of the immune response paralleled the degradation rate of the carrier. Formulations based on slow, resorbing PLG maintained relatively constant peak antibody levels for 26 weeks and high titres for over 1 year at a level approximating the peak response to the faster resorbing, OVA-loaded particles which was of lower duration. Vaccine formulations prepared by simple mixing of blank PLG microparticles and OVA exhibited low primary immune responses which were only elevated by boosting. OVA-loaded PLG microparticles exhibited a substantial surface protein component amounting to ca 40% and 60% of the total protein loading for slow resorbing and fast resorbing PLG, respectively. These findings suggest that sustained presentation of surface protein to the immune system was a major factor in the induction and long-term maintenance of high antibody titres following a single s.c. administration of OVA-loaded microparticles. Copyright (C) 1996 Elsevier Science Ltd.
引用
收藏
页码:1429 / 1438
页数:10
相关论文
共 35 条
  • [1] CONTROLLED-RELEASE VACCINES - BIODEGRADABLE POLYLACTIDE POLYGLYCOLIDE (PL/PG) MICROSPHERES AS ANTIGEN VEHICLES
    AGUADO, MT
    LAMBERT, PH
    [J]. IMMUNOBIOLOGY, 1992, 184 (2-3) : 113 - 125
  • [2] DETERMINANTS OF RELEASE RATE OF TETANUS VACCINE FROM POLYESTER MICROSPHERES
    ALONSO, MJ
    COHEN, S
    PARK, TG
    GUPTA, RK
    SIBER, GR
    LANGER, R
    [J]. PHARMACEUTICAL RESEARCH, 1993, 10 (07) : 945 - 953
  • [3] ALPAR HO, 1994, EUR J PHARM BIOPHARM, V40, P198
  • [4] ADSORPTION OF D-NAL(2)6LHRH, A DECAPEPTIDE, ONTO GLASS AND OTHER SURFACES
    ANIK, ST
    HWANG, JY
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1983, 16 (02) : 181 - 190
  • [5] CHALLACOMBE SJ, 1992, IMMUNOLOGY, V76, P164
  • [6] THE PHARMACOKINETICS OF, AND HUMORAL RESPONSES TO, ANTIGEN DELIVERED BY MICROENCAPSULATED LIPOSOMES
    COHEN, S
    BERNSTEIN, H
    HEWES, C
    CHOW, M
    LANGER, R
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (23) : 10440 - 10444
  • [7] Coombes A. G. A., 1994, Clinical Materials, V17, P35
  • [8] BIODEGRADABLE AND BIOCOMPATIBLE POLY(DL-LACTIDE-CO-GLYCOLIDE) MICROSPHERES AS AN ADJUVANT FOR STAPHYLOCOCCAL ENTEROTOXIN-B TOXOID WHICH ENHANCES THE LEVEL OF TOXIN-NEUTRALIZING ANTIBODIES
    ELDRIDGE, JH
    STAAS, JK
    MEULBROEK, JA
    TICE, TR
    GILLEY, RM
    [J]. INFECTION AND IMMUNITY, 1991, 59 (09) : 2978 - 2986
  • [9] BIODEGRADABLE MICROSPHERES AS A VACCINE DELIVERY SYSTEM
    ELDRIDGE, JH
    STAAS, JK
    MEULBROEK, JA
    MCGHEE, JR
    TICE, TR
    GILLEY, RM
    [J]. MOLECULAR IMMUNOLOGY, 1991, 28 (03) : 287 - 294
  • [10] PARAMETERS AFFECTING THE IMMUNOGENICITY OF MICROENCAPSULATED TETANUS TOXOID
    ESPARZA, I
    KISSEL, T
    [J]. VACCINE, 1992, 10 (10) : 714 - 720