Dual-Route Influenza Immunization for Mucosal and Systemic Immunity
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Solution Overview
Problem
Current influenza vaccines are sensitive to strain mismatches and less effective at preventing viral transmission, necessitating the development of novel immunization strategies that are less sensitive to strain mismatches and more effective at preventing transmission.
Innovation Solution
A method involving parenteral administration of a first composition to elicit systemic T and/or B cell responses, followed by intranasal, inhalational, intratracheal, or intrabronchial administration of a viral protein to establish tissue-resident T and/or B cell responses, with optional boosting using the same or a third composition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional inactivated virus-based vaccines are used for parental administration, then systemic immunity is established, but the vaccines are sensitive to strain mismatches and less effective at preventing viral transmission
Solution Approach 1:
The vaccine strategy is segmented into two distinct components: a parenteral vaccine for systemic immunity and a mucosal booster for local respiratory tract immunity. This segmentation allows each component to target specific immune compartments, with the parenteral route establishing systemic T and B cell responses while the mucosal route establishes tissue-resident memory cells and secretory IgA at the site of viral entry, thereby reducing sensitivity to strain mismatches
Solution Approach 2:
The invention adds a spatial dimension to vaccination by targeting both systemic circulation (parenteral route) and mucosal surfaces (intranasal/inhalational route). This dual-route approach creates immunity in two different anatomical dimensions, ensuring protection both systemically and at the specific mucosal interface where influenza viruses infect, thus improving adaptability to various strains
2Reliability
If conventional flu vaccines are administered, then protection against severe symptoms is achieved when correctly matched, but effectiveness at preventing viral transmission is much reduced
Solution Approach 1:
The mucosal booster acts as an intermediary that bridges systemic immunity and local mucosal defense. By administering viral proteins or weakened live virus through the mucosal route, the vaccine establishes tissue-resident memory T and B cells along with secretory IgA at the respiratory mucosa, which serves as the first line of defense to block viral entry and transmission before the virus can systemically infect
Solution Approach 2:
The mucosal booster component performs preliminary action by establishing local immune defenses at the respiratory tract mucosa before viral exposure. This preliminary establishment of tissue-resident memory cells and secretory IgA creates a pre-positioned immune barrier that can immediately respond to and block viral entry, preventing transmission before systemic infection occurs
Data Source
AI summary
Described herein is a method of treating, ameliorating, and/or preventing an influenza viral infection in a subject, and/or immunizing a subject against an influenza viral infection, which include parenterally administering to the subject a first composition including a first compound in an amount sufficient to elicit systemic T and/or B cell response(s) against a first influenza virus in the subject; and administering to the subject a second composition including a viral protein of a second influenza virus through an administration route comprising intranasal, inhalational, intratracheal, intrapulmonary, and intrabronchial, in an amount sufficient to result in establishment of tissue-resident T cell(s), tissue-resident B cell(s), mucosal IgA, and/or systemic IgG specific against the influenza viral infection in the subject. Also described are a kit for performing the method, as well as methods and kits for boosting existing immunity against influenza viral infections.