A Th1-Inducing Adjuvant, MPL<sup>®</sup>, Enhances Antibody Profiles in Experimental Animals Suggesting It Has the Potential to Improve the Efficacy of Allergy Vaccines
Bibliographic record
Abstract
BACKGROUND: Monophosphoryl lipid A (MPL) is a detoxified derivative of the lipopolysaccharide (LPS) moiety of Salmonella minnesota R595, which has retained immunostimulatory activities. MPL has been administered to many subjects in clinical trials as an adjuvant component of infectious disease vaccines and is currently a component of a licensed cancer vaccine, Melacine (Corixa Inc., Schering Plough). MPL has, in particular, been shown to promote Th1-type antigen specific responses. L-tyrosine is a depot adjuvant which is fully metabolisable and has been successfully employed in allergy vaccines for a number of years. METHODS: Mice were immunised with MPL adjuvant in conjunction with separate preparations of either ovalbumin or glutaraldehyde-modified ragweed pollen extract both coprecipitated with L-tyrosine. The specific antibody isotypes IgG1, IgG2a, IgG2b and also IgE were measured. Rats received booster injections of keyhole limpet haemocyanin (KLH) in conjunction with MPL adjuvant following priming with KLH in alum alone. KLH-specific antibody responses were measured. RESULTS: It was shown that a combination of L-tyrosine and MPL were synergistic in enhancing murine antigen specific IgG antibody responses without enhancing antigen specific IgE responses. Furthermore, this adjuvant combination promoted strong IgG2 antigen specific responses indicative of a Th1 directed response. In KLH sensitised rats, treatment with MPL was shown to prevent a secondary IgE antibody response when injected with booster injections of antigen. CONCLUSIONS: Immunisation of mice with two different antigens adsorbed to L-tyrosine induced a Th1-skewed primary response when in conjunction with MPL adjuvant which also generally enhances a specific IgG response. Incorporation of MPL adjuvant in the immunisation of rats prevented a secondary specific IgE response. These results suggest that the employment of this new adjuvant in clinical allergy vaccination formulations may result in an improved efficacy which could be utilised in various ways to improve compliance.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".