16 October 2020 - - The US Food and Drug Administration to begin a Phase I clinical trial of hAd5-COVID-19, US-based immunotherapy company ImmunityBio, Inc's novel COVID-19 vaccine candidate that targets both the inner nucleocapsid (N), engineered to activate T cells, and outer spike (S) protein, engineered to activate antibodies against the coronavirus (SARS-CoV-2), the company said.

These dual constructs (bivalent sequences) of SARS-CoV-2 offer the potential for the hAd5 vaccine to provide recipients with durable, long-term cell-mediated immunity with potent antibody stimulation against both the S and N proteins.

The company anticipates launching a Phase I trial at Irvine, Calif. based Hoag Hospital this month with adult subjects up to age 55.

The hAd5-COVID-19 vaccine candidate is a novel, engineered, second-generation human adenovirus serotype 5 vaccine.

Because it delivers both the S and N proteins, the vaccine has the potential to enable recipients to develop immune "memory," promoting long-lasting immunity to SARS-CoV-2.

The N protein has been engineered with a novel signaling domain to enhance T cell activation. The hAd5 vaccine with this Enhanced T cell Signaling Domain has generated potent CD4+ and CD8+ COVID specific T cell activation recognizing S and N following hAd5 vaccination in pre-clinical studies.

ImmunityBio's approach differs from first-generation adenoviral platforms, including one based on the chimpanzee adenovirus and the first-generation human adenovirus vaccines being tested in Europe, China, Russia and the United States.

All first-generation COVID-19 vaccines in late-stage clinical trials deliver only the monovalent spike protein on the surface of the virus and therefore focus primarily on antibody protection as their primary endpoints.

Current first-generation adenovirus platforms suffer from the disadvantage of generating neutralizing antibodies which occur after repeated administration, resulting in the attack of the adenovirus vector itself and reduce the effectiveness of the vaccine.

ImmunityBio's hAd5 second generation adenovirus platform has four deletions which overcome pre-existing adenoviral immunity allowing for multiple administrations.

This ability to circumvent pre-existing adenoviral immunity has been demonstrated in multiple Phase I / II clinical trials of hAd5 showing tumor specific CD4+ and CD8+ T cells following repeated administrations in the presence of pre-existing adenovirus immunity.

ImmunityBio plans to administer the hAd5-COVID-19 vaccine both as a prime and boost to sustain protection against SARS-CoV-2 since multiple re-immunizations using the same vector platform are now possible with the novel hAd5 platform.

The company is also pursuing preclinical development for oral, inhalational and intranasal administration to provide mucosal immunity in addition to durable humoral and cell-mediated immunity against COVID-19.

The Phase I, open-label, dose-ranging study will be conducted in healthy adults aged 18 to 55 years old. The study's primary objective is to examine the safety and reactogenicity of two-doses of the vaccine.

Additionally, immunogenicity, duration of immune response and occurrence of symptomatic COVID-19 will be measured.