Vaccine Formulation Selective Antigen Adsorption
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing vaccine compositions face challenges in maintaining the immunogenicity of Hepatitis B surface antigen (HBsAg) while preventing the adsorption of Haemophilus influenzae type b (Hib) antigen on aluminum oxyhydroxide, as the addition of anions to avoid adsorption of Hib antigen leads to desorption of HBsAg.
Innovation Solution
A process involving the adsorption of HBsAg on aluminum oxyhydroxide, followed by mixing with Hib antigen in the presence of cationic amino acids and phosphate ions, specifically at concentrations of 35 to 45 mMol/l, to maintain HBsAg adsorption while keeping Hib antigen non-adsorbed.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If phosphate ions are added to prevent Hib antigen adsorption on aluminum oxyhydroxide, then Hib antigen immunogenicity is maintained, but HBsAg desorbs from aluminum oxyhydroxide
Solution Approach 1:
The patent applies local quality by creating distinct chemical microenvironments: aluminum oxyhydroxide particles with adsorbed HBsAg are kept separate from free phosphate ions that would cause desorption. The Hib antigen is prevented from adsorbing to aluminum oxyhydroxide through controlled addition of phosphate ions at specific concentrations (10-50 mM), while HBsAg remains bound to aluminum oxyhydroxide surface sites. This spatial and chemical differentiation allows simultaneous maintenance of both antigen properties.
Solution Approach 2:
The patent utilizes parameter changes by precisely controlling phosphate ion concentration (10-50 mM range), pH (6.5-7.5 range), and aluminum oxyhydroxide particle surface charge characteristics. By adjusting these parameters, the patent achieves a state where phosphate ions sufficiently compete with Hib antigen for aluminum binding sites (preventing Hib adsorption) but do not completely displace HBsAg from the surface. The specific phosphate concentration range is critical: too low allows Hib adsorption, too high causes HBsAg desorption.
2Reliability
If Hib antigen is adsorbed on aluminum salts to enhance immunogenicity, then immunogenicity improves, but immunogenicity is lost over time
Solution Approach 1:
The patent extracts the harmful adsorption interaction between Hib antigen and aluminum oxyhydroxide by introducing phosphate ions that preferentially bind to aluminum sites. The phosphate ions act as a blocking agent, occupying aluminum binding sites and preventing Hib antigen from forming stable adsorption complexes. This extraction of the problematic adsorption mechanism allows Hib antigen to remain in solution without losing immunogenicity over time, while still benefiting from the aluminum adjuvant effect.
3Stability of the object's composition
If HBsAg is adsorbed on aluminum oxyhydroxide to maintain stability, then stability is maintained, but addition of anions causes desorption
Solution Approach 1:
The patent applies preliminary anti-action by pre-establishing a controlled phosphate ion environment before Hib antigen addition. The phosphate ions are added at concentrations (10-50 mM) and pH levels (6.5-7.5) that create a protective chemical context: they sufficiently occupy aluminum sites to prevent Hib adsorption but maintain HBsAg binding through optimal electrostatic conditions. This preliminary setup prevents the harmful desorption effect that would otherwise occur with anion addition.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The vaccine composition remains immunogenic for up to 36 months, with at least 60% of HBsAg and 65% of Hib antigen maintaining their respective states, ensuring stability and effectiveness.
Implementation Method 1
the hepatitis B surface antigen is adsorbed on AlOOH in order to obtain an AlOOH/HBsAg complex
Implementation Method 2
the AlOOH/HBsAg complex is mixed with the Hib antigen in the presence of cationic amino acids at a concentration of at least 100 mg/l, and Phosphate ions at a concentration of 35 to 45 mMol/l
Data Source
AI summary
The subject matter of the invention is a method for preparing a vaccine composition comprising at least aluminium oxyhydroxide (AlOOH), and at least the hepatitis B surface antigen and the Haemophilus influenzae type b antigen. According to the invention, the hepatitis B surface antigen is kept adsorbed on the AlOOH, whereas the Hib antigen is kept nonadsorbed. To this end: the hepatitis B surface antigen is adsorbed onto AlOOH in order to obtain an AlOOH/HBsAg complex, then - said AlOOH/HBsAg complex is mixed with the Hib antigen in the presence of cationic amino acids at a concentration of at least 100 mg/l, and of phosphate ions at a concentration of 35 to 45 mMol/l.