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Species-specific immune response to immunization with human versus rodent A beta peptide.


Year of Publication:
Contact PI Name:
Cynthia A. Lemere
Contact PI Affiliation:
Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Timothy J. Seabrook, Jeanne K. Bloom, Melitza Iglesias, Edward T. Spooner, Dominic M. Walsh
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Study Goal and Principal Findings:

Amyloid beta (A beta) immunization of amyloid precursor protein (APP)-transgenic (tg) mice with human A beta induces humoral immunity, however, the immune response to endogenous rodent A beta is unknown. Fourteen-month J20 APP-tg mice and non-tg littermates were immunized subcutaneously followed by chronic intranasal boosting with human or rodent A beta peptide and adjuvant LT(R192G). Rodent A beta-immunized APP-tg mice had anti-rodent A beta antibody levels of 257.8 micrograms/ml and those immunized with human A beta had anti-human A beta antibodies of 120.8 micrograms/ml. Non-tg littermates had anti-rodent and anti-human A beta antibody concentrations of 98.8 and 231.1 microgram/ml, respectively. Inter-species cross-reactivity was minimal. Anti-human A beta antibodies were predominately IgG1 and IgG2b, while anti-rodent A beta antibodies were equally IgG1, IgG2a, and IgG2b. Anti-human A beta antibodies recognized an epitope within human A beta1-9. Anti-rodent A beta antibodies did not stain Alzheimer's disease (AD) plaques but bound some plaques in APP-tg mice. Splenocytes proliferated modestly to their respective antigen and secreted low levels of IL-2 and IFN-gamma. Therefore, immunizing APP-tg and non-tg mice with rodent A beta resulted in a species-specific humoral response with modest T cell reactivity.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
Human beta Amyloid Peptide
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
Rodent beta Amyloid Peptide
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Activated Microglia
beta Amyloid Deposits
beta Amyloid Load
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Brain-Buffer Insoluble beta Amyloid Peptide 40
Brain-Buffer Insoluble beta Amyloid Peptide 42
Interleukin 2 (IL-2)
Interleukin 4 (IL-4)
Interleukin 5 (IL-5)
Interferon (IFN) gamma
Major Histocompatibility Antigens Class 2 (MHC II)
Cell Biology
Neuroprotection-Amyloid Neurotoxicity
Cell Proliferation
Anti-beta Amyloid Antibody Titers
IgG Antibody Titers
Anti-beta Amyloid Antibody Isotypes
Epitope Mapping
Antibody Avidity
Antibody Target Specificity
T Cell Response
Interferon (IFN) gamma Production
Plasma-Complex of Antibody and beta Amyloid
Plasma-beta Amyloid Peptides
Target Engagement (Binding beta Amyloid Antibodies to beta Amyloid Deposits)
Target Engagement (Reduction beta Amyloid Peptides-Brain)
Target Engagement (Reduction beta Amyloid Peptides-Plasma)
Lymphatic Infiltration