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.
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 populationi.
“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 (Anktiva™), 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/
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version on businesswire.com: https://www.businesswire.com/news/home/20201109005457/en/
Jen Hodson NANT Jen@nant.com 562-397-3639
NantKwest (NASDAQ:NK)
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