As the SARS-CoV-2 virus has spread around the world, it has developed mutations that result in new variants of the virus. These variations are concentrated in the so-called “Spike” protein used by the virus to gain entry to the body’s cells. This variability has the potential to allow the virus to remain in long-term circulation in humans around the world. The spike also is the protein that is the target of the antibodies generated by current COVID-19 vaccines; so as variants arise, the effectiveness of these vaccines can be reduced.
To deal with the long-term, endemic presence of the virus, ImmunityBio is developing universal booster vaccine candidates that target both the spike protein and the nucleocapsid protein that coats the virus’s genetic material (RNA) – and which has little variation. This approach has the potential to provide enhanced protection against current and future SARS-CoV-2 variants. Several peer-reviewed studies demonstrate that patients who recovered from SARS-CoV in the 2003 outbreak possess long lasting memory T cells reactive to the nucleocapsid protein of SARS-CoV 17 years after infection. While antibodies block infection when present, T cells are vital for long-term immune memory.
Our vaccine candidates do not require the difficult storage conditions of several current vaccines, making them more practical to make, store, and distribute to remote areas. Their potential to be more resilient than current vaccines also means that fewer doses would be required to provide longer-term immunity, further reducing the complications and costs that now prevent much of the world from being vaccinated.
About Our COVID-19 Studies
ImmunityBio is addressing the serious need for a booster vaccine by conducting multiple COVID-19-related studies, two in South Africa and two in the U.S.
The Phase 1 ProViva Trial (AW-001-ProViva), which began in February of 2021 and is our first trial in South Africa, was designed to test the safety and immunogenicity of our lead COVID-19 vaccine candidate, hAd5 S+N, as a subcutaneous shot in a small number of healthy volunteers. The Trial was amended to include those with prior COVID-19 infections to allow our vaccine to serve as a boost to natural infection. The trial is ongoing with participant follow up for a full year from time of vaccination.
Our second trial, the Phase 1/2 South Africa Sisonke T-Cell Universal Boost trial (COVID-4.010), is, to our knowledge, among the first randomized control trials to study a heterologous boost and utilizes our hAd5 S+N vaccine as a subcutaneous shot in participants who previously received a single S-only vaccination. The endpoints of the trial are to examine whether the boost could generate additional immune responses and potentially reduce breakthrough infections currently occurring in South Africa at a rapid rate.
Our US trials QUILT 4.001 and 4.005 (NCT04591717, NCT04732468) are studying the safety, reactogenicity, and immunogenicity of the hAd5 S+N vaccine candidate. These trials are currently in follow-up phase and formal reports on safety and immunogenicity are being prepared for the FDA.
About ImmunityBio’s hAd5 T-Cell-Based, Viral-Vector Vaccine Candidate
Our second-generation hAd5 viral-vector vaccines are unique in targeting both S and N SARS-CoV-2 proteins to generate B and T cell memory to these antigens and, potentially, long-term immunity to the virus. Most of the COVID-19 vaccines approved by the FDA or in late-stage clinical trials deliver only the S protein which, by some estimates, has already mutated thousands of times.
Another unique characteristic of the hAd5 design is the use of a second-generation hAd5 platform that was developed to elicit anti-SARS-CoV-2 immune responses even in Ad-immune individuals, meaning subjects can receive the vaccine multiple times, if necessary. The stimulation of anti-hAd5 immune responses is attenuated with the second-generation platform in comparison with the first-generation platforms due to additional genetic deletions, allowing the immune system response to focus on the inserted antigens (in this case Spike and Nucleocapsid).
Finally, ImmunityBio’s novel hAd5 vaccine candidates have been developed for different routes of administration: subcutaneous (SC) injection, sublingual (SL) drops, and intranasal (IN) spray.
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.