Encapsulation in biodegradable microparticles enhances serum antibody response to parenterally-delivered β-amyloid in mice

Poly(lactide-co-glycolide) (PLG) microspheres were tested as a parenteral delivery system for human β-amyloid (1–42) (Aβ), a potential immunotherapeutic undergoing assessment in Phase 1 studies for Alzheimer's disease (AD). Aβ was successfully encapsulated in PLG microspheres of average sizes o...

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Bibliographic Details
Published in:Vaccine 2001-07, Vol.19 (30), p.4185-4193
Main Authors: Brayden, David J., Templeton, Louise, McClean, Siobhan, Barbour, Robin, Huang, Jiping, Nguyen, Minh, Ahern, Deirdra, Motter, Ruth, Johnson-Wood, Kelly, Vasquez, Nicki, Schenk, Dale, Seubert, Peter
Format: Article
Language:English
Subjects:
Adjuvants
Alzheimer's disease
Amyloid beta-Peptides - administration & dosage
Amyloid beta-Peptides - immunology
Animals
Antibodies - blood
Applied microbiology
Biodegradation, Environmental
Biological and medical sciences
Dose-Response Relationship, Immunologic
Fundamental and applied biological sciences. Psychology
Immunization
Mice
Microbiology
Microspheres
Particle Size
Poly(lactide-co-glycolide)
Polyglactin 910 - administration & dosage
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Virology
β Amyloid
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Summary:Poly(lactide-co-glycolide) (PLG) microspheres were tested as a parenteral delivery system for human β-amyloid (1–42) (Aβ), a potential immunotherapeutic undergoing assessment in Phase 1 studies for Alzheimer's disease (AD). Aβ was successfully encapsulated in PLG microspheres of average sizes of 3 or 15 μm diameter. Swiss Webster (SW) mice were injected by the sub-cutaneous (s.c.) or intra-peritoneal (i.p.) routes with 3–33 μg Aβ. Aβ-PLG microparticles (3 μm) induced dose-dependent antibody responses, which were maximal at 33 μg Aβ, while Aβ in phosphate-buffered saline (PBS) produced weak antibody responses at the same doses by both routes. Significantly increased antibody responses were seen for both small and large particle formulations given by the i.p. route in comparison to the s.c route. It was previously reported that passive immunisation with Aβ-specific antibodies cleared amyloid plaques in a mouse model of AD (Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid β-peptide enter the nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature Med 2000;6:916–19), an indication that induction of serum antibody is a prerequisite for efficacy.
ISSN:0264-410X
1873-2518
DOI:10.1016/S0264-410X(01)00162-1