Mucosal Vaccine Priming Boosting Strategy
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Solution Overview
Problem
Current vaccines are poor inducers of mucosal immunity and are less effective against respiratory pathogen infections at mucosal surfaces due to inadequate measurement of antibody doses and labor-intensive recovery of mucosal T cells, limiting the approval of mucosal vaccines for human use.
Innovation Solution
A method involving a nucleic acid-based expression system encoding a protein antigen of a respiratory pathogen, where a priming composition is administered non-mucosally and a boosting composition is administered mucosally, specifically for respiratory syncytial virus (RSV), using a polynucleotide vector and adjuvants like CpG and MPL for intranasal delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If injected vaccines are used, then systemic immunity is induced, but mucosal immunity is poorly induced and less effective against mucosal surface infections
Solution Approach 1:
The vaccine program is segmented into two distinct phases: a systemic priming phase using intramuscular injection of nucleic acid-based expression system, followed by a mucosal boosting phase using intranasal administration of protein antigen with adjuvants. This segmentation allows each phase to target different immune compartments optimally.
Solution Approach 2:
The systemic priming vaccination is administered first to establish baseline immunity and primed immune cells before the mucosal boosting phase. This preliminary action prepares the immune system to respond more effectively to the subsequent mucosal antigen exposure.
2Measurement precision
If mucosal vaccine is administered, then mucosal immune response is induced, but antibody dose measurement is difficult and T cell recovery is labor intensive
Solution Approach 1:
The patent incorporates specific adjuvants (CpG oligonucleotides and monophosphoryl lipid A) as intermediaries in the mucosal boosting composition. These adjuvants enhance and standardize the immune response, making it more predictable and measurable, thereby facilitating antibody dose assessment and immune response evaluation.
3Reliability
If only a few mucosal vaccines are approved, then safety is maintained, but effectiveness against respiratory pathogen infections is limited
Solution Approach 1:
The patent employs a dynamic two-phase vaccination strategy where the immune response is progressively enhanced from systemic to mucosal immunity. This dynamic approach allows for controlled safety assessment in the priming phase while achieving enhanced protective effectiveness in the boosting phase.
Solution Approach 2:
The mucosal boosting composition uses a composite formulation combining protein antigen with specific adjuvants (CpG and monophosphoryl lipid A). This composite material synergistically enhances immunogenicity while maintaining safety through the use of well-characterized adjuvant components.
Data Source
AI summary
A method of vaccinating a subject against a respiratory viral infection comprises concurrently or separately administering to a subject in need thereof one of more polynucleotide vector(s) encoding a respiratory virus antigen and one or more aerosolized respiratory virus antigen(s) to induce a mucosal immune response in the subject against an infection by respiratory viral infection. In another aspect, the present application provides a mucosal vaccine kit comprising one of more polynucleotide vector(s) encoding a respiratory virus antigen, one or more aerosolized respiratory virus antigen(s).