Lipid Nanoparticle Vaccine Composition for CD8+ T Cell Modulation
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Solution Overview
Problem
There is a need for tools to augment the immune response induced by nucleic acid-based lipid nanoparticle (LNP) vaccines and drive appropriate immune responses for protection against pathogens, as well as optimize the vaccine dose and number of doses required, given the differential induction of SARS-CoV-2-specific CD8+ T cell responses by different LNPs.
Innovation Solution
Lipid nanoparticles (LNPs) comprising nucleoside-modified RNA encoding an antigen and a cytokine or immune receptor, such as IL-27 or IL-12, are used to elicit a modulated immune response, enhancing or decreasing CD8+ T cell responses as needed.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If LNP-mRNA vaccines are used to induce immune response, then protective antibody and T cell responses are promoted, but the ability to modulate the type and magnitude of immune response is limited
Solution Approach 1:
The vaccine composition is segmented into multiple functional components: antigen-encoding mRNA for target recognition, cytokine-encoding mRNA (e.g., IL-27, IL-12) for immune response type modulation, and ionizable lipid for delivery. This segmentation allows independent optimization of each component to achieve desired immune responses.
Solution Approach 2:
The patent utilizes parameter changes in mRNA sequence design (nucleoside modifications, codon optimization, 5' and 3' UTR sequences) to control the magnitude and duration of protein expression, thereby modulating the immune response. Different mRNA parameters are adjusted to elicit Th1, Th2, or Th17 responses as needed.
2Reliability
If higher vaccine doses or additional doses are administered, then immune response magnitude increases, but the number of doses and total dose required increases
Solution Approach 1:
Cytokines such as IL-27 and IL-12 are introduced as intermediary molecules that mediate between the antigen presentation and T cell activation stages. These cytokines amplify the immune signal, allowing lower antigen doses to achieve the same immune response magnitude as higher doses without adjuvants would require.
Solution Approach 2:
The cytokine-encoding mRNA is co-delivered with antigen-encoding mRNA to preemptively establish the appropriate immune milieu before antigen presentation. This preliminary action of cytokine expression primes the immune system to respond more strongly and efficiently to the antigen, reducing the required antigen dose.
3Productivity
If LNP composition is optimized for delivery, then mRNA delivery efficiency improves, but control over the type of immune response (Th1, Th2, Th17) is limited
Solution Approach 1:
The LNP delivery system is designed with multi-functionality: it provides efficient cellular uptake and endosomal escape (delivery function) while also serving as a platform for co-delivering multiple mRNA species with different immune-modulating properties (modulation function). The ionizable lipid composition is optimized to support both roles simultaneously.
Solution Approach 2:
The vaccine employs composite mRNA constructs where antigen-encoding and cytokine-encoding RNAs are delivered together in a single LNP formulation. This composite approach combines the delivery efficiency of LNPs with the immune-modulating properties of cytokines, achieving both high delivery efficiency and precise immune response type control.
Data Source
AI summary
The invention includes lipid nanoparticles (LNP) capable of eliciting a modulated immune response against an antigen in a subject. The LNPs comprise: (a) at least one first nucleoside-modified ribonucleic acid (RNA) encoding an antigen; (b) at least one second nucleoside-modified RNA encoding a cytokine or immune receptor (such as but not limited to a cytokine receptor); and (c) at least one ionizable lipid. The invention also includes pharmaceutical compositions comprising the LNP of the invention, as well as a method of eliciting a modulated immune response against an antigen in a subject, the method comprising administering an effective amount of a pharmaceutical compositions comprising the LNP of the invention.