Document 0616
 DOCN  M9440616
 TI    New advances in vaccine delivery systems.
 DT    9404
 AU    Eldridge JH; Staas JK; Chen D; Marx PA; Tice TR; Gilley RM; Department
       of Medicine, University of Alabama at Birmingham.
 SO    Semin Hematol. 1993 Oct;30(4 Suppl 4):16-24; discussion 25. Unique
       Identifier : AIDSLINE MED/94135267
 AB    Successful application of the next generation of vaccines will require
       that protection be induced with a minimal number of administrations, and
       that a practical approach to inducing immunity at mucosal surfaces be
       developed. For these reasons, vaccine-containing microspheres were
       formulated from the biodegradable and biocompatible copolymer
       poly(DL-lactide-co-glycolide) [DL-PLG]. Subcutaneous immunization of
       mice with 1- to 10-microns microspheres containing a toxoid vaccine of
       staphylococcal enterotoxin B (SEB) induced a 500-fold potentiation of
       the circulating antitoxin response. Strong adjuvant activity was
       dependent on the microspheres being no more than 10 microns in diameter
       and required that the antigen was within the particles. The rate of
       DL-PLG biodegradation is a function of the ratio of lactide to
       glycolide, and the co-injection of SEB toxoid microspheres formulated
       with two different DL-PLG ratios stimulated both a primary and an
       anamnestic secondary antitoxin response. When it was administered by the
       oral or intratracheal (IT) route, microencapsulated SEB toxoid was found
       to be effective in the induction of concurrent circulating and
       disseminated mucosal antibody responses. Female rhesus macaques
       immunized with a microencapsulated simian immunodeficiency virus (SIV)
       vaccine produced high levels of circulating anti-SIV antibodies, and
       following oral or IT boosting, specific antibodies were found in vaginal
       wash fluids. Vaginal challenge with viable homologous SIV resulted in
       the infection of three out of four nonimmunized but only one out of
       seven microsphere-immunized macaques. Thus, DL-PLG microspheres are a
       promising approach to the delivery of vaccines, combining adjuvant
       activity with controlled release and effective presentation to mucosally
       associated lymphoid tissues (MALT).
 DE    Adjuvants, Immunologic  Animal  Biodegradation  Drug Administration
       Schedule  *Drug Delivery Systems  Macaca mulatta  Microspheres  Mucous
       Membrane/IMMUNOLOGY  Support, U.S. Gov't, Non-P.H.S.  Support, U.S.
       Gov't, P.H.S.  Vaccines/*ADMINISTRATION & DOSAGE  JOURNAL ARTICLE
       REVIEW  REVIEW, TUTORIAL

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