ImmunityBio, Inc. a privately-held, clinical-stage immunotherapy company, announced positive study results for their human Ad5 (hAd5) COVID-19 vaccine candidate, which shows memory T-cell recall from patients previously infected with SARS-CoV-2 virus. The ability to stimulate SARS-CoV 2 specific T-cells, which recognize the N and S proteins, is a crucial part of the novel design of ImmunityBio’s vaccine candidate. The antibody- and T cell-based vaccine seeks both to provide protection for the uninfected population and also the potential to clear virally infected cells in infected subjects. It is unclear how long antibodies may provide protection. With the production of both antibodies and T cells, the potential exists for long-term, durable immunity. The results of this study were published in medRxiv (“Th1 Dominant Nucleocapsid and Spike Antigen-Specific CD4+ and CD8+ Memory T Cell Recall Induced by hAd5 S-Fusion + N-ETSD Infection of Autologous Dendritic Cells from Patients Previously Infected with SARS-CoV-2”).
ImmunityBio’s vaccine candidate targets both the spike (S) and nucleocapsid (N) proteins (hAd5 S + N) of SARS-CoV-2 to activate a multi-pronged attack by the immune system. This is distinct from most vaccine candidates currently in late-stage clinical trials, which target S alone. Recent reports suggest that antibodies to S may be vulnerable to reduced effectiveness because of emerging new mutations, as well as uncertainty over the longevity of the antibody response over time. The hAd5 bivalent COVID-19 vaccine induces T cell immunity and could provide long-term protection against the virus as the antibodies wane over time.
An additional distinctive feature of the ImmunityBio vaccine candidate design is its use of a second-generation human adenovirus serotype 5 (hAd5) that has been shown to effectively deliver antigens even in the presence of preexisting adenovirus immunity which is present in up to roughly 60% of the population[i].
“As the virus continues to spread at an alarming rate, it is important that we develop COVID-19 vaccines that not only provide the population with protection from new infection through antibodies that block viral entry into cells, but also establish a robust T cell immune response to clear the virus from infected cells,” said Patrick Soon-Shiong, M.D., Chairman and CEO of ImmunityBio. “This study suggests that our vaccine candidate has the potential to both serve as a protective vaccine for the uninfected population, and, potentially, also as a therapeutic to enhance the speed of viral clearance in the newly diagnosed, positively infected patient by T cell clearance of infected cells. We plan to study this hypothesis in our ongoing clinical trials to explore whether by stimulating SARS-CoV-2-specific T cells, our vaccine could induce rapid clearance of the virus from a newly diagnosed patient, and reduce the risk of airborne transmission from infected patients to healthy contacts.”
The manuscript detailing these preclinical data is available on preprint server medRxiv at [https://www.medrxiv.org/content/10.1101/2020.11.04.20225417v1] and is concurrently undergoing scientific peer-review for potential publication.
A previously announced preclinical study showed that ImmunityBio’s hAd5 S-Fusion + N-ETSD (hAd5 COVID-19) vaccine candidate elicits both T-cell immunity and neutralizing antibodies in a murine pre-clinical model [“ImmunityBio Study Shows Positive T Cell and Antibody Immune Responses to its COVID-19 Vaccine Candidate that Targets Both Spike and Nucleocapsid Virus Proteins”]. The present study demonstrates the CD4+ and CD8+ memory T cells of previously infected SARS-CoV-2 patients, but not unexposed individuals, recognize SARS-CoV-2 antigens expressed by hAd5 S-Fusion + N-ETSD infected dendritic cells in vitro. These data support the hypothesis that SARS-CoV-2 antigens delivered to cells by the next generation hAd5 platform are expressed in human cells in a conformationally relevant manner and available to elicit an adaptive immune response, critical for vaccine efficacy.