Successful adjuvant-free vaccination of BALB/c mice with mutated amyloid beta peptides.
BACKGROUND
A recent human clinical trial of an Alzheimer's disease (AD) vaccine using amyloid beta (Abeta) 1-42 plus QS-21 adjuvant produced some positive results, but was halted due to meningoencephalitis in some participants. The development of a vaccine with mutant Abeta peptides that avoids the use of an adjuvant may result in an effective and safer human vaccine.


RESULTS
All peptides tested showed high antibody responses, were long-lasting, and demonstrated good memory response. Epitope mapping indicated that peptide mutation did not lead to epitope switching. Mutant peptides induced different inflammation responses as evidenced by cytokine profiles. Ig isotyping indicated that adjuvant-free vaccination with peptides drove an adequate Th2 response. All anti-sera from vaccinated mice cross-reacted with human Abeta in APP/PS1 transgenic mouse brain tissue.


CONCLUSIONS
Our study demonstrated that an adjuvant-free vaccine with different Abeta peptides can be an effective and safe vaccination approach against AD. This study represents the first report of adjuvant-free vaccines utilizing Abeta peptides carrying diverse mutations in the T-cell epitope. These largely positive results provide encouragement for the future of the development of human vaccinations for AD.
Cao
Chuanhai
C
Johnnie B, Byrd Alzheimer's Center and Research Institute, 4001 E, Fletcher Ave,, Third Floor, Tampa, FL 33613, USA. ccao@byrdinstitute.org
Lin
Xiaoyang
X
Wahi
Monika M
MM
Jackson
Eugene A
EA
Potter
Huntington
H
D023582:Alzheimer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000818:Animals; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D018604:Epitope Mapping; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D016207:Cytokines; D007074:Immunoglobulin G