COVID-19 Clinical Trial
COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was first identified in December 2019. As of February 2021, the virus had infected 107 million people and killed more than 2.3 million globally.
Transmission of SARS-CoV-2 typically occurs through direct or close contact with infected people via their saliva or respiratory droplets, which are expelled when they cough, sneeze, talk, or sing. The SARS-CoV-2 particle is inhaled and eventually brushes against a nasopharyngeal or lung cell with an ACE2 receptor on its surface. The virus’s spike protein (S) binds to ACE2 to infect these cells, allowing the virus to enter and use the cell’s machinery to copy itself and make people sick. Most COVID-19 vaccines (both FDA-approved and those in late-stage clinical trials) deliver only the spike protein, which has already mutated several times; this is why these first-generation vaccines are less effective against variants. These mutations allow the virus to escape immune responses directed against it.
At ImmunityBio, we are trying to activate the immune system to reduce transmission of SARS-CoV-2 and stop escape mutants. We have created a unique second-generation viral-vector vaccine hAd5 that targets both spike (S) and nucleocapsid (N) SARS-CoV-2 proteins to generate B and T cell memory to these antigens and prevent escape mutants from eluding the immune system.
This unique hAd5 design uses a second-generation hAd5 platform developed to elicit anti-SARS-CoV-2 immune responses, even in Ad-immune individuals, meaning subjects can receive the vaccine multiple times, if necessary. In addition, in partnership with UK-based biotechnology company iosBio, we have developed the vaccine into room temperature-stable oral capsules, potentially solving the cold-chain challenges of distribution affecting many of the current COVID-19 vaccines.
In a 2020 study sponsored by the Biomedical Advanced Research & Development Authority (BARDA), ImmunityBio’s hAd5 T-cell-based vaccine candidate (subcutaneous injection and room temperature-stable oral capsules) inhibited SARS-CoV-2 virus replication to undetectable levels and cleared infection within days in vaccinated NHPs. Blocked viral replication was observed in lung and nasal passages, critical for reducing transmission of the virus from immunized recipients to others.
One Vaccine, Three Trials, Three Routes of Immune Protection
The first two cohorts of the Phase Ib, open-label, dose-ranging study (NCT04591717) of the vaccine received low and intermediate dose levels. Participants received two subcutaneous injections 21 days apart. No grade three or four AEs and no SAEs were observed at either dose level and, in the intermediate dose group, immunogenicity was observed as early as 14 days after the prime. An additional 40 subjects will be enrolled to evaluate safety, reactogenicity, and immunogenicity of the combination of hAd5 in four different cohorts of sublingual and subcutaneous formulations to select an optimal combination dose for future studies.
The second Phase 1b trial (NCT04732468) will assess the safety, reactogenicity, and immunogenicity of the combination of hAd5 in oral capsule and subcutaneous formulations; it will also determine an optimal dosage for future studies. Up to 65 subjects will be enrolled in the four-cohort study, anticipated to begin in Q1.
A Phase I trial has also been initiated in Cape Town, South Africa (NCT04710303; COVID-19 Vaccination Using a 2nd Generation Adenoviral Platform in Healthy South African Adults) to assess the safety, reactogenicity, and immunogenicity of the hAd5 vaccine and select a dose for future studies. Trials using sublingual delivery and room temperature-stable oral capsules are anticipated to follow.
We believe that the key to creating long-term immunity to the SARS-CoV-2 virus and overcoming the variants that are rapidly developing around the world is to design a vaccine that activates not only antibodies but also memory B and T cells to multiple antigens. Furthermore, room temperature-stable formulations for oral delivery have the potential to solve the cold-chain challenges of distribution, and the ability to generate mucosal IgA antibody barriers to the virus in the upper respiratory tract where it first enters the body.