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Successful adjuvant-free vaccination of BALB/c mice with mutated amyloid beta peptides.

Cao C, Lin X, Wahi MM, Jackson EA, Potter H - BMC Neurosci (2008)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Johnnie B, Byrd Alzheimer's Center and Research Institute, 4001 E, Fletcher Ave,, Third Floor, Tampa, FL 33613, USA. ccao@byrdinstitute.org

ABSTRACT

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.

Conclusion: 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.

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Related in: MedlinePlus

Antibody detection after 3 inoculations with different Aβ peptides. Note: ELISA result for antibody detection at 1:1024 dilutions using Aβ1–42 wild type as capture antigen at 10 μg/ml (50 μl/well) (n = 4 in each group). Ctr = Control, PWT = Wild type Aβ1–42, PFM = Aβ1–42 with Flemish mutation, PDM = Aβ1–42 with Dutch mutation, PFDM = Aβ1–42 with Flemish and Dutch mutation, P22W = Aβ1–42 with novel mutation at 22, P24M = Aβ1–42 with novel mutation at 24 amino acid.
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Figure 1: Antibody detection after 3 inoculations with different Aβ peptides. Note: ELISA result for antibody detection at 1:1024 dilutions using Aβ1–42 wild type as capture antigen at 10 μg/ml (50 μl/well) (n = 4 in each group). Ctr = Control, PWT = Wild type Aβ1–42, PFM = Aβ1–42 with Flemish mutation, PDM = Aβ1–42 with Dutch mutation, PFDM = Aβ1–42 with Flemish and Dutch mutation, P22W = Aβ1–42 with novel mutation at 22, P24M = Aβ1–42 with novel mutation at 24 amino acid.

Mentions: Mutated and Wt Aβ1–42 peptide vaccinations induced clear antibody responses after 2 inoculations (data not shown) and high antibody level after 3 inoculations, while no antibody could be detected in the control group (Figure 1). There was a high antibody response 10 days after the third vaccination for all peptide vaccine groups at 1:1024 dilutions, and antibody titers rose to greater than 1:4096 in all peptide vaccine groups (data not shown). There were no differences in peptide recognition among various anti-sera and peptides, with the exception of Wt (PWT) and P24M (novel mutation), which were higher regardless of coating antigen (Figure 2). Antibody was long-lasting, showing duration of up to 4 months (Figure 3). Memory response was also apparent when comparing antibody levels before and after boosting (Figure 4).


Successful adjuvant-free vaccination of BALB/c mice with mutated amyloid beta peptides.

Cao C, Lin X, Wahi MM, Jackson EA, Potter H - BMC Neurosci (2008)

Antibody detection after 3 inoculations with different Aβ peptides. Note: ELISA result for antibody detection at 1:1024 dilutions using Aβ1–42 wild type as capture antigen at 10 μg/ml (50 μl/well) (n = 4 in each group). Ctr = Control, PWT = Wild type Aβ1–42, PFM = Aβ1–42 with Flemish mutation, PDM = Aβ1–42 with Dutch mutation, PFDM = Aβ1–42 with Flemish and Dutch mutation, P22W = Aβ1–42 with novel mutation at 22, P24M = Aβ1–42 with novel mutation at 24 amino acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2270279&req=5

Figure 1: Antibody detection after 3 inoculations with different Aβ peptides. Note: ELISA result for antibody detection at 1:1024 dilutions using Aβ1–42 wild type as capture antigen at 10 μg/ml (50 μl/well) (n = 4 in each group). Ctr = Control, PWT = Wild type Aβ1–42, PFM = Aβ1–42 with Flemish mutation, PDM = Aβ1–42 with Dutch mutation, PFDM = Aβ1–42 with Flemish and Dutch mutation, P22W = Aβ1–42 with novel mutation at 22, P24M = Aβ1–42 with novel mutation at 24 amino acid.
Mentions: Mutated and Wt Aβ1–42 peptide vaccinations induced clear antibody responses after 2 inoculations (data not shown) and high antibody level after 3 inoculations, while no antibody could be detected in the control group (Figure 1). There was a high antibody response 10 days after the third vaccination for all peptide vaccine groups at 1:1024 dilutions, and antibody titers rose to greater than 1:4096 in all peptide vaccine groups (data not shown). There were no differences in peptide recognition among various anti-sera and peptides, with the exception of Wt (PWT) and P24M (novel mutation), which were higher regardless of coating antigen (Figure 2). Antibody was long-lasting, showing duration of up to 4 months (Figure 3). Memory response was also apparent when comparing antibody levels before and after boosting (Figure 4).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Johnnie B, Byrd Alzheimer's Center and Research Institute, 4001 E, Fletcher Ave,, Third Floor, Tampa, FL 33613, USA. ccao@byrdinstitute.org

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus