Tendel Therapies Inc.

Memory-promoting Ad Vaccine for Long-lived Protection Against SARS-COV-2 - This Grant Will Establish Immunologic Proof-of-concept for a Second-generation SARS-COV-2 Vaccine Providing Extraordinarily Durable T-cell and Antibody Responses, Which Together Protect the Respiratory Mucosa and Minimize the Risk of Antibody-dependent Enhancement (ade). the Vaccine Platform Combines the Immunostimulatory Power and Proven Safety of Adenovirus-vectored Vaccines With Novel in- Vector Adjuvants and a Robust Humoral Component. in Particular, Our Preliminary Data Show That This Vaccine Candidate Stimulates T-cell Responses in Macaques That Are Virtually Undiminished Ten Months After Vaccination. We Hypothesize That a Memory-promoting Adenovirus (MPAD) Drives Robust CD4+ T-cell Responses to Sars- COV-2 That Provide Both Airway-resident Protection and Superior B-cell Helper Function. Aim 1: Demonstrate Robust, Durable CD4+ T-cell Responses to Mpad/n Vaccination, Localized to Airways and Exceeding Responses Seen With Conventional Ad Vectors. Here We Test If Key Differentiating Features of Tendel’s Memory-promoting Ad Vaccine, Previously Demonstrated for Immunization Against Siv Gag, Are Also Seen When Immunizing Against SARS-COV-2 Nucleocapsid. Our Hypothesis Predicts Balanced CD4 and CD8 Responses With Effector-memory Character and Localization to Airways, Which Are Maintained With Minimal Dimunition Throughout the Experiment. Milestone 1: Demonstrate Superiority of Mpad Vaccine for Eliciting SARS-COV-2-SPECIFIC T Cells in Airways. Aim 2: Evaluate SARS-COV-2 Neutralizing Antibodies and Subtypes in Rhesus Macaques Receiving Ad/rbd VS. Mpad/rbd. Tendel Aims to Provide a Second-generation SARS-COV-2 Vaccine That Evades Any Tendency to Enhancement by Combining Appropriate T-cell and B-cell Responses. Some Previous Reports Have Demonstrated Enhanced Extrinsic Ade for TH2-ASSOCIATED Antibodies of the IGG1 Class, as Well as Intrinsic Ade That Is Linked to TH2-ASSOCIATED Effector Mechanisms, Especially IL-10. in This Aim We Test the Antibody Subclasses and Capacity for Enhancement of Antibodies Elicited by Ad/rbd VS. Mpad/rbd, to Determine the Best Component for Inclusion in a Second-generation Vaccine. Milestone 2: Choose an Optimal B Cell-targeted Vaccine Component, Which Does Not Mediate Ade, for Combination With an Mpad-based T-cell Component. These Innovative Phase I Experiments Will Be Sufficient to Establish Both the Technical Merit And—in Light of the Proven Commercial and Government Interest in Ad-vectored Vaccination Against SARS-COV-2—THE Commercial Potential of Tendel’s Approach.