MVA Vaccine Expressing UL128 Complex for HCMV Neutralizing Antibodies
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current vaccines for human cytomegalovirus (HCMV) lack effectiveness in preventing infection, particularly in epithelial and endothelial cells, which are crucial for horizontal and vertical transmission, and existing vaccines fail to induce robust neutralizing antibodies (NAb) against these cell types.
Innovation Solution
Development of an expression system and vaccine composition that includes a viral vector, such as modified vaccinia Ankara (MVA), expressing the UL128 complex (UL128C), which comprises UL128, UL130, UL131A, glycoprotein H, and glycoprotein L, to prevent HCMV entry into cells by stimulating neutralizing antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing vaccines are used, then general immunization is provided, but neutralizing antibodies against epithelial and endothelial cells are not induced
Solution Approach 1:
The vaccine targets specific cell types (epithelial and endothelial cells) through cell-type-specific antigens rather than providing general immunization. This segmentation approach focuses the immune response on the specific cell types involved in horizontal and vertical transmission, resolving the contradiction between reliability for specific cell types and versatility across multiple cell types.
Solution Approach 2:
The invention uses cell-type-specific antigens that are expressed locally in epithelial and endothelial cells. By targeting antigens specifically associated with these cell types, the vaccine induces neutralizing antibodies that are locally effective against the specific transmission-relevant cells, rather than providing uniform protection across all cell types.
2Reliability
If a viral vector expressing UL128 complex is used, then neutralizing antibodies are induced against epithelial and endothelial cells, but vaccine complexity increases
Solution Approach 1:
The viral vector system serves multiple functions: it delivers the UL128 complex antigens, expresses them in appropriate cell types, and stimulates the immune system to produce neutralizing antibodies. This multi-functionality reduces overall system complexity by consolidating multiple steps into a single platform, despite the inherent complexity of viral vector technology.
3Reliability
If current vaccine approaches are used, then general immune response is generated, but protection against horizontal and vertical transmission is insufficient
Solution Approach 1:
The invention changes the key parameter of antigen selection to include cell-type-specific antigens (UL128 complex) that are specifically associated with epithelial and endothelial cells. This parameter change shifts the immune response from general to targeted, providing reliable protection against both horizontal and vertical transmission routes by focusing on the specific cellular mechanisms involved in each transmission type.
Data Source
AI summary
In one embodiment, an expression system for expressing a UL128 complex is provided herein. The expression system may include a bacterial artificial chromosome (BAC) construct, wherein the BAC construct comprises a viral vector inserted with a set of DNA sequences that encode a UL128 complex. In another embodiment, a vaccine composition for preventing HCMV infection is provided. The vaccine composition may include a viral or bacterial vector capable of expressing a UL128 complex and a pharmaceutically acceptable carrier, adjuvant, additive or combination thereof or additional vector expressing a protein adjuvant. The viral vector may be an MVA and the UL128 complex includes five HCMV proteins or antigenic fragments thereof: UL128, UL130, UL131A, gL, and gH. In some embodiments, the viral vector is further inserted with one or more additional DNA sequences that encode one or more additional HCMVHCMV proteins or antigenic fragments thereof such as pp65, gB or both, or such as gM/gN or gO.