P3‐047: The Amyloid‐Beta (Aβ) Oligomer‐Specific CYCLIC‐SER‐ASN‐LYS (CSNK) Tripeptide is Highly Immunogenic and Induces Sustained Levels of ANTI‐CSNK Antibodies of the IGG1 Subclass
Bibliographic record
Abstract
Amyloid beta Oligomers (AβO) are key mediators of the neurotoxic, neuropathologic and behavioral changes characteristic of Alzheimer’s Disease (AD). We identified an AβO-specific epitope, cyclized serine-asparagine-lysine (cSNK), and generated mouse monoclonal antibody 5E3 (mAb5E3) and a humanized version (h5E3) targeting this epitope. We have demonstrated the specificity and selectivity of mAb5E3 for soluble synthetic and native AβOs, and its non-reactivity with monomers and fibrils. Consequently, APP/PS1 mice immunized with cSNK generated AβO-specific antibodies with concomitant decreases in plaque burden, reduced amyloid propagation and ameliorated memory deficits. In continuance with developing the cSNK tripeptide as a potential vaccine, our current work further elucidates key attributes of the humoral immune response in cSNK-immunized mice: long-term temporal profile and immunoglobulin (Ig) isotype/subclass distribution. The study consisted of 76 sex-matched APP/PS1 mice, 38 vaccinated with 100 μg of cSNK-KLH/ Emulsigen-D adjuvant, and 38 with adjuvant only beginning at 3 months of age. Animals were thereafter treated monthly for 12 months and plasma collected prior to each immunization. Anti-cSNK antibodies were detected using a Molecular Affinity Screening System (MASS-1) (Sierra Sensors, Germany), a high throughput surface plasmon resonance imaging analytical biosensor. cSNK-BSA was immobilized on a sensorchip and serial samples of all mice injected. In a subsequent experiment, the Ig isotype/subclass distribution of serial samples of 20 mice were evaluated: diluted plasma were injected, followed by injections of goat anti-mouse IgA, IgM, IgG, IgG1, IgG2a, IgG2ab, IgG2c and IgG3. Adjuvant-treated mice had no detectable antibodies to cSNK, whilst all cSNK-immunized mice generated high levels of anti-cSNK antibodies commencing at 4 weeks post-vaccination, age month 4. Peak antibody levels were attained at 8 weeks post-vaccination, age month 5, after which levels varied and declined slightly but remained substantially higher than levels at month 4. Ig isotype/ subclass analysis revealed that anti-cSNK antibodies are overwhelmingly of the IgG isotype and predominantly of the IgG1 subclass. Immunization of APP/PS1 mice with the cSNK tripeptide induces high and sustained levels of anti-cSNK antibodies that demonstrated binding to AβO. Anti-cSNK antibodies are predominantly of the IgG1 isotype, this being indicative of a Th2 immune response.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".