Chimeric PIV3 Viral Vector for SARS-CoV-2 Mucosal Immunity
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Solution Overview
Problem
Developing effective vaccines for SARS-COV-2 and HPIV3 is challenging due to the immaturity of the immune system in infants, immune suppression by maternal antibodies, and the need for mucosal immunity in the respiratory tract, with existing vaccines lacking direct stimulation of local immunity at the primary infection site.
Innovation Solution
Recombinant chimeric bovine/human parainfluenza virus 3 (rB/HPIV3) vectors expressing the SARS-COV-2 Spike protein are used to induce an immune response, which are infectious, attenuated, and self-replicating, allowing for intranasal immunization and potentially coordinating with other vaccines, with specific proline substitutions to stabilize the protein and ablate the furin cleavage site.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If parenteral immunization is used for SARS-COV-2 vaccination, then vaccine delivery is simple and effective, but local immunity in the respiratory tract is not directly stimulated
Solution Approach 1:
The patent uses a recombinant parainfluenza virus 3 (PIV3) as an intermediary vector to deliver the SARS-CoV-2 spike protein antigen directly to the respiratory tract. The PIV3 virus serves as a mediator that can infect respiratory epithelial cells and express the antigen locally, thereby stimulating mucosal immunity while maintaining ease of administration through intranasal or intratracheal delivery.
Solution Approach 2:
The recombinant PIV3 vector is designed to be self-replicating in the respiratory tract, allowing it to autonomously produce and express the SARS-CoV-2 spike protein antigen at the site of infection. This self-service capability enables the vaccine to actively stimulate local immune responses without requiring external assistance or repeated administrations.
2Ease of operation
If conventional vaccines are used for infants, then vaccination can be administered, but immune response is limited due to immune system immaturity and maternal antibody suppression
Solution Approach 1:
The patent employs a recombinant viral vector system that changes the delivery parameters and antigen presentation method to overcome infant immune system limitations. The PIV3 vector expresses the SARS-CoV-2 spike protein with specific mutations (K986P, V987P) to stabilize it in a prefusion conformation, enhancing immunogenicity. The vector can be administered via multiple routes (intranasal, intratracheal, intramuscular, subcutaneous) to bypass maternal antibody interference and stimulate both humoral and cellular immune responses effectively in infants.
Data Source
AI summary
Recombinant chimeric bovine/human parainfluenza virus 3 (rB/HPIV3) vectors expressing a recombinant Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) protein as well as methods of their use and manufacture, are provided. The rB/HPIV3 vector comprises a genome comprising a heterologous gene encoding the recombinant SARS-COV-2 S protein. Nucleic acid molecules comprising the sequence of the genome or antigenome of the disclosed rB/HPIV3 vectors are also provided. The disclosed rB/HPIV3 vectors can be used, for example, to induce an immune response to SARS-COV-2 and HPIV3 in a subject.