Multivalent Enterovirus Vaccine Composition for Broad Neutralizing Antibody Response
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Solution Overview
Problem
The development of an effective vaccine against human rhinoviruses (HRV) is hindered by the large number of serotypes (>100), leading to poor human responses to existing vaccines, as seen with 10-valent rhinovirus vaccines, which induce antibodies against only a limited number of serotypes.
Innovation Solution
A multivalent vaccine composition comprising inactivated or attenuated HRV serotypes, along with recombinantly produced HRV strains or capsid proteins, representing multiple serotypes, is administered with adjuvants like aluminum hydroxide or alum to induce a protective immune response against multiple HRV serotypes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a multivalent vaccine comprising multiple HRV serotypes is administered, then the breadth of neutralizing antibody responses is improved, but the complexity of the vaccine composition increases
Solution Approach 1:
The patent combines multiple HRV serotypes (including rare and emerging serotypes) into a single multivalent vaccine formulation. This merging approach allows the vaccine to elicit broad neutralizing antibody responses across numerous serotypes simultaneously, addressing the contradiction by achieving wide adaptability through integration of multiple viral components in one composition.
Solution Approach 2:
The multivalent vaccine composition is designed to provide universal protection against diverse HRV serotypes through a single administration. The vaccine exhibits multi-functionality by inducing neutralizing antibodies that recognize and neutralize multiple serotypes, including those not traditionally covered by existing vaccines, thereby achieving broad adaptability without requiring multiple separate vaccine formulations.
2Reliability
If inactivated or attenuated HRV serotypes are used in the vaccine composition, then the protective immune response is improved, but the manufacturing complexity increases
Solution Approach 1:
The patent employs inactivated or attenuated HRV serotypes, representing changes in the viral parameters (loss of infectivity while retaining antigenicity). This parameter change allows the vaccine to maintain protective immune response generation capability while reducing the risk of viral replication and disease, balancing reliability with manufacturability through controlled viral inactivation or attenuation processes.
Solution Approach 2:
The vaccine utilizes recombinant capsid proteins as copies of the viral structure without requiring live or inactivated whole viruses. This copying approach simplifies manufacturing by using protein subunits that can be produced through recombinant DNA technology, while still eliciting protective immune responses against the actual viruses, thus reducing manufacturing complexity while maintaining reliability.
3Quantity of substance
If higher input virus concentrations are used, then the titer of neutralizing antibodies is improved, but the risk of viral inactivity or degradation increases
Solution Approach 1:
The patent optimizes the input virus concentration parameters to achieve high neutralizing antibody titers while maintaining viral activity. By carefully controlling the concentration and incorporating stabilizing formulations, the vaccine ensures that higher virus inputs translate to enhanced immune responses without compromising viral integrity or inducing degradation, thus balancing quantity with reliability.
Solution Approach 2:
The vaccine formulation includes adjuvants and stabilizing agents that act as intermediaries between the virus particles and the immune system. These intermediaries enhance the effectiveness of the viral antigens, allowing high virus concentrations to be used without direct risk of inactivity or degradation. The adjuvants mediate the interaction between the viral components and host immune cells, ensuring reliable viral activity even at optimized high concentrations.
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 multivalent vaccine composition induces broad neutralizing antibody responses against multiple HRV serotypes, providing long-lasting protection for up to 24 months, as demonstrated in mouse and rhesus macaque models, with high titers achieved even with higher input virus concentrations.
Implementation Method 1
comprising inactivated or attenuated viruses of more than 10 serotypes of the Enterovirus genus and aluminum hydroxide, aluminum phosphate, alum (potassium aluminum sulfate), or mixtures thereof
Data Source
AI summary
This disclosure relates to multivalent enterovirus vaccine compositions and uses related thereto. In certain embodiments, the disclosure relates to vaccine compositions comprising multivalent, mixtures of enterovirus (for example HRV) serotypes or recombinantly produced variants or recombinantly produced viral capsid proteins. In certain embodiments, the disclosure relates to methods of immunization comprising administering an effective amount of compositions disclosed herein to a subject diagnosed with, exhibiting symptoms of, or at risk of an enterovirus infection.