Study shows hAd5 S+N COVID-19 vaccine candidate, which delivers two distinct proteins, stimulates T-cell responses of volunteers recovered from SARS-CoV-2 infection, demonstrating that the S and N antigens from the vaccine are recognized by SARS-COV-2 reactive human T cells

  • Study results suggest this next-generation human adenovirus 5 (hAd5) vaccine, which delivers both spike (S) and nucleocapsid (N) SARS-CoV-2 proteins, stimulates memory CD4+ and CD8+ T-cells, both of which may be critical for clearing virus infected cells.
  • Together with earlier studies in pre-clinical models, which demonstrate the vaccine’s immunogenicity, these findings support the further use of this vaccine as a therapeutic in newly infected patients to limit lateral transmission of the disease.
  • T-cell response may provide long-term immunity and mitigate waning short-lived antibodies against the coronavirus.

CULVER CITY, Calif., November 9, 2020 – ImmunityBio, Inc. a privately-held, clinical-stage immunotherapy company, today 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.

About the Phase I Clinical Trial

ImmunityBio and NantKwest are currently enrolling 35 healthy adults aged 18 to 55 years old in the Phase 1 study for the hAd5-COVID-19 vaccine candidate (NCT04591717). hAd5-COVID-19 will be administered as both a prime and boost using the same vector platform to enable sustained protection against SARS-CoV-2. The study’s main objective is to examine the safety of and reactogenicity to two doses of the vaccine. The companies are also pursuing development for oral, inhalational, and intranasal administration of hAd5.

For more information about the trial or to enroll in it, please contact clinicalresearch@hoag.org.

About the Second-Generation hAd5 Adenovirus Platform

Based on ImmunityBio’s ongoing development of an adenovirus-based vaccine for the treatment of cancer (The NANT Cancer Vaccine), the company has developed a unique second-generation COVID-19 vaccine, distinctive in multiple aspects of design from the current COVID-19 vaccines in late stage clinical trials, including the (1) vector platform, (2) the immunogenic SARS-CoV-2 proteins selected, (3) the balanced antibody and T cell immune activation based on molecular trafficking of the SARS-CoV-2 protein, (4) addressing multiple modes of administration to achieve mucosal, antibody and long-term cell mediated immunity, and (5) overcoming cold-chain limitations by developed refrigerated and room-temperature stable vaccines.

A.Scientific differentiation of hAd5 over existing adenoviral vector approaches:
Compared to current adenovirus vector platforms in Phase 3 clinical trials for COVID-19, ImmunityBio’s hAd5 has four deletions, enabling delivery of the transgene COVID-19 proteins even in the presence of pre-existing adenovirus immunity. Clinical studies in cancer patients have shown the capability of inducing CD4+ and CD8+ T cell responses following multiple subcutaneous injections of hAd5 in patients with proven adenoviral immunity.

B.Demonstrated use of hAd5 vector delivery platform for other potential outbreaks of known viruses as well as novel or previously unrecognized viruses, with demonstrated capability for rapid development, pre-clinical testing and GMP manufacture
ImmunityBio has reported the successful rapid development of hAd5 as a vaccine during the H1N1 outbreak in 2009. Details will be discussed below. In addition, ImmunityBio has published on the successful pre-clinical development of vaccines for HIV, SIV, Chikungunya, Lassa Fever, and, Influenza.
C.NANT Cancer Vaccine and QUILT Clinical Trials:
ImmunityBio has studied the hAd5 platform extensively in over 150 patients with cancer across 13 Phase 1 / 2 trials. The transgenes expressed include: hAd5-CEA, hAd5-PSA, hAd5-MUC1, hAd5-Brachyury. In these studies at the National Cancer Institute (NCI) and academic centers, successful antigen specific CD4+ and CD8+ T cells were induced even in the presence of previous adenoviral immunity. These studies, a component of the NANT Cancer Vaccine and QUILT clinical trials, are ongoing.

About ImmunityBio and NantKwest Joint Collaboration Agreement

Under the terms of a definitive agreement announced on August 24, 2020, ImmunityBio, Inc. and its affiliate NantKwest, Inc. (NASDAQ: NK) agreed to share equally the costs of development, manufacturing, marketing and commercialization of the products each is developing related to COVID-19, including the hAd5 vaccine candidate. Should a product be commercialized successfully, the companies have agreed to a 60-40 percentage split of net profits, with the larger share going to the company that developed the product. The agreement also details the structure of shared governance of the joint collaboration.

About ImmunityBio 

ImmunityBio, Inc. is a late-stage immunotherapy company developing next-generation therapies that drive immunogenic mechanisms for defeating cancers and infectious disease. The company’s immunotherapy platform activates both the innate (natural killer cell and macrophage) and adaptive (T cell) immune systems to create long-term “immunological memory.” This novel approach is designed to eliminate the need for high-dose chemotherapy, improve upon the outcomes of current CAR T-cell therapies, and extend beyond checkpoint inhibitors.

ImmunityBio has established three fundamental platforms to drive long term immunological memory. These include first-in-class antibody cytokine fusion proteins, synthetic immune modulators, and second-generation vaccine vector platforms.

ImmunityBio’s lead cytokine infusion protein, a novel interleukin-15 (IL-15) superagonist complex (AnktivaÔ), has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for BCG-unresponsive CIS non-muscle invasive bladder cancer (NMIBC). Other indications currently at registration-stage trials include BCG-unresponsive papillary bladder cancer, first- and second-line lung cancer, triple-negative breast cancer, metastatic pancreatic cancer, recurrent glioblastoma, and soft tissue sarcoma in combination with the company’s synthetic immune modulator (Aldoxorubicin).

ImmunityBio is also developing therapies, including vaccines, for the prevention and treatment of HIV, influenza, and the coronavirus SARS-CoV-2 with its second-generation human adenovirus (hAd5) vaccine platform.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements concerning or implying that ImmunityBio will be successful in improving the treatment of various diseases, including, but not limited to the novel coronavirus and cancer. Risks and uncertainties related to this endeavor include, but are not limited to, the company’s beliefs regarding the success, cost, and timing of its development activities and clinical trials.

Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law.

[i] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443060/