Official Title
A Randomised, Controlled, Phase 1 Study to Evaluate the Safety and Immunogenicity of a Candidate Adjuvanted Recombinant Protein SARS-COV-2 Vaccine in Healthy Adult Subjects
Brief Summary

This is a study to test a new vaccine (Covax-19) against COVID-19. COVID-19 is a potentially deadly disease that is caused by a new strain of coronavirus called SARS-CoV-2. To date, SARS-CoV-2 has infected over 4 million people worldwide resulted in the deaths of over three hundred thousand people.

Detailed Description

Human infections with zoonotic coronaviruses including severe acute respiratory syndrome

coronavirus (SARS CoV), Middle East respiratory syndrome-associated coronavirus (MERS CoV)

and now 2019 SARS-CoV-2, all pose major human public health threats with high case fatality

rates. The outbreak of SARS-CoV-2, which shares high similarity with SARS-CoV in its viral

genome, has so far caused more than 4,736,000 cases worldwide (as of May 17, 2020) with

3131,545 deaths, resulting in an estimated overall mortality rate of 4-5%. It has a

particularly high mortality rate in elderly people and those with chronic disease. To fight

the current outbreak and prepare for future human outbreaks of similar coronaviruses,

development of a safe and effective SARS-COV-2 vaccine remains a high priority. The fatality

rate in the elderly is very high, being 8% for those over 70 and over 20% for those over 80.

Notably, over 16% of the Australian population is aged 65 or older. Currently there is no way

to control infection with SARS-COV-2 other than minimise exposure by social isolation.

Development of a vaccine against COVID-19 would deliver major public health and economic

benefits for Australia, with potential to prevent numerous deaths, particularly among the

Australian elderly, reducing the burden on hospital ICUs, helping to alleviate public

concern, and ultimately allowing the Australian economy to return as fast as possible to


SARS-CoV and SARS-CoV-2 are both closely related enveloped, single positive-stranded RNA

viruses, with one genome encoding a non-structural replicase polyprotein and structural

proteins, including spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. SARS

virus neutralizing antibodies were shown to be directed against the S protein. S protein can

be cleaved into S1 and S2 subunits by proteases and within the S1 subunit there is a

receptor-binding domain (RBD), which was shown to bind angiotensin-converting enzyme 2

(ACE2), which mediates SARS virus entry into cells. SARS-CoV-2 spike protein similarly binds

ACE2 for cellular entry. Hence a recombinant SARS-CoV-2 spike protein vaccine that induces

neutralising antibody against the virus should be effective against SARS-CoV-2 infection just

as seen for SARS CoV.

SARS-COV-2 vaccine design is best informed by previous experience with closely related SARS

CoV vaccines. Antibodies against the coronavirus spike protein blocks infection. When

recombinant SARS spike protein vaccines produced in insect cells were formulated with Advax

adjuvant, this enhances neutralizing antibody and T cell responses which translate into rapid

lung viral clearance. Based on experience with developing successful and safe SARS and MERS

vaccines, Covax-19 vaccine design is based on recombinant insect cell- expressed SARS-COV-2

spike protein formulated with Advax-SM adjuvant. The vaccine is based on recombinant

expression of the ecto-domain of spike protein in insect cells. Insect cell expression of

recombinant protein is a well characterised platform, allowing standardised procedures to be

rapidly transferred to other facilities around the world. In response to the 2009 H1N1

influenza pandemic, roll-out of a pandemic vaccine based on hemagglutinin protein was

extremely fast, with the first cGMP batches of vaccine produced within 6 weeks of virus

discovery, and the first human trial subject dosed at Flinders just under 3 months after

virus discovery . The use of Advax adjuvant doubled the seroconversion and seroprotection

rates while maintaining vaccine tolerability and safety. Recombinant proteins manufactured

using this method and formulated with Advax adjuvants have been found to be effective and

safe in multiple human trials, including of H1N1/2009 and H5N1 (NCT02335164) and H7N9

(NCT03038776) influenza vaccines.

Covax-19 consists of highly purified recombinant SARS-COV-2 spike protein plus Advax-SM

adjuvant in a sterile solution for intramuscular injection. COVAX-19™ vaccine is manufactured

using a Sf9 platform. Advax-CpG adjuvant has previously been well tolerated and effective in

trials of hepatitis B, H5N1 (NCT02335164) and H7N9 (NCT03038776) influenza vaccines and has

recently been tested by the NIH in a US multicentre clinical trial with 2 quadrivalent

seasonal influenza vaccines (NCT03945825).

COVAX-19™ vaccine is designed to elicit an immune response against SARS-CoV-2 with generation

of neutralising antibodies against its spike protein that prevent the virus attaching to the

human ACE2 receptor in the respiratory epithelium. It is also designed to induce T cells

against the spike protein.

Study hypotheses

- COVAX-19 vaccine is safe and well tolerated in adult human subjects

- COVAX-19 vaccine will induce durable high titer neutralising antibodies and T cell

responses against SARS-COV-2 virus.

Coronavirus Infection

Biological: COVID19 vaccine
COVID19 recombinant spike protein with Advax-SM adjuvant
Group A
Other Name: COVAX-19 vaccine

Biological: Saline
Saline control
Group B
Other Name: Saline control

Eligibility Criteria

Inclusion criteria - Are males or non-pregnant females, 18 years of age or older. - Provide written informed consent prior to initiation of any study procedures. - Are able to understand and comply with planned study procedures and be available for all study visits. - Are in good health as determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations in the opinion of the Investigator. - Screening laboratory bloods - White Blood Cells (WBC), Hemoglobin (Hgb), Platelets (PLTs), Alanine Aminotransferase (ALT), Total Bilirubin (T. Bili), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), and Creatinine (Cr)) are within acceptable parameters as determined by the Investigator - Women of childbearing potential must use an acceptable contraception method and must have a negative urine or serum pregnancy test within 24 hours prior to the first study vaccination.

Exclusion criteria - Have an acute illness, as determined by the site Principal Investigator (PI) or appropriate sub-investigator, within 72 hours prior to study vaccination. - Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation. *Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. - Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy. - Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination. - Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted. - Have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection. - Have known hypersensitivity or allergy to insect stings or other components of the study vaccine. - Have a history of severe reactions following previous immunization with licensed or unlicensed vaccines. - Have a history of Guillain-Barré Syndrome. - Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination. - Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs). - Have a history of alcohol or drug abuse within 5 years prior to study vaccination. - Have any diagnosis, current or past, of schizophrenia, bipolar disease or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations as determined by the site PI or appropriate sub-investigator. - Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to study vaccination. - Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination. - Have taken high-dose inhaled corticosteroids within 30 days prior to study vaccination. - Have a known history of documented COVID-19 infection within the past 6 months. - Received an experimental agent within 30 days prior to the study vaccination or expect to receive another experimental agent during the trial-reporting period. - Female participants who are breastfeeding or plan to breastfeed from the time of the first study vaccination through 30 days after the last study vaccination. - Any participant whose enrolment, in the opinion of the investigator, would be detrimental to the participant or the study.

Eligibility Gender
Eligibility Age
Minimum: 18 Years~Maximum: 65 Years

Nikolai Petrovsky, MBBS, Ph.D

David Gordon, MBBS, Ph.D

David Gordon, MBBS, Ph.D
Principal Investigator

Vaxine Pty Ltd
Central Adelaide Local Health Network Incorporated
NCT Number
MeSH Terms
Coronavirus Infections
Severe Acute Respiratory Syndrome