Yeast Lysate Immunogenic Composition for CTL Activation
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Solution Overview
Problem
Current vaccines, particularly subunit and recombinant live virus vaccines, fail to elicit protective cellular immunity, and existing adjuvants are limited in their ability to stimulate cytotoxic T lymphocyte (CTL) responses, which are crucial for combating viruses, intracellular pathogens, and cancers.
Innovation Solution
Development of a yeast lysate-based immunogenic composition lacking yeast membranes and cell walls, combined with a whole recombinant yeast vehicle, to enhance antigen presentation and activation of antigen-presenting cells, thereby increasing CTL responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If subunit vaccines or recombinant live virus vaccines are used to stimulate humoral immunity, then antibody response is improved, but cellular immunity and CTL responses are insufficient
Solution Approach 1:
The patent combines intact yeast cells expressing antigens with yeast lysates in a single vaccine composition. The intact yeast provide structural framework and membrane presentation, while the lysate contains released cytoplasmic antigens and molecular patterns that strongly activate dendritic cells. This merging of both forms enables simultaneous induction of robust humoral and cellular immunity, resolving the contradiction between antibody response and cellular immunity.
Solution Approach 2:
The patent utilizes the different functional states of yeast cells by transitioning from intact cellular form to lysed form. The lysate preparation releases intracellular contents including cytoplasmic antigens and danger signals that are sequestered in intact cells. This parameter change from intact to lysed state enhances the activation of antigen-presenting cells and T cell priming, thereby improving cellular immunity while maintaining humoral response.
2Quantity of substance
If conventional adjuvants are used to stimulate immune responses, then humoral immunity is improved, but CTL responses and cell-mediated immunity are not effectively stimulated
Solution Approach 1:
The yeast-based composition serves multiple functions simultaneously: the intact yeast and lysate components collectively provide antigen presentation, activate dendritic cells through molecular patterns, and induce both humoral and cellular immunity. The system is self-sufficient in providing both adjuvant-like activation signals and antigen delivery, eliminating the need for separate adjuvants that fail to stimulate CTL responses.
Solution Approach 2:
The patent creates a composite immunogenic composition combining intact yeast cells with yeast lysates. This composite structure integrates the advantages of both forms: the structural integrity and membrane presentation of intact yeast with the released cytoplasmic contents and activation signals of lysates. The composite material simultaneously engages B cell and T cell responses, overcoming the limitation of conventional single-form adjuvants.
3Ease of manufacture
If yeast cells are used to produce protein antigens, then recombinant protein expression is achieved, but the yeast cells or subcellular fractions do not effectively prime protective cellular immunity when delivered to patients
Solution Approach 1:
The patent segments the yeast cell into two functional components for the vaccine: intact yeast cells that maintain structural integrity and membrane presentation, and yeast lysates that contain released cytoplasmic antigens and molecular patterns. This segmentation allows each component to fulfill specific functions - intact cells provide stable antigen presentation while lysates provide potent activation signals - together achieving protective cellular immunity that neither form could achieve alone.
Data Source
AI summary
Disclosed are immunogenic pharmaceutical compositions comprising yeast lysates for inducing cellular immune responses, methods of making immunogenic compositions comprising yeast lysates, methods of treatment comprising administration of said compositions, and kits comprising said yeast lysate compositions. Disclosed immunogenic compositions further comprise an antigen heterologous to the yeast, and may comprise whole yeast and immunostimulatory agents. Induced cellular immune responses comprise cytotoxic T cell activation with specificity to the antigen comprising the immunogenic composition. Various methods of formulation and administration to a patient are described herein, especially wherein the patient suffers from an infectious disease and/or cancer.