Monovalent Recombinant COVID19 Vaccine
Condition: Coronavirus Infection; COVID
MeSH terms: Coronavirus Infections
Study type: Interventional
Phase: Phase 1

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
      normal.

      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.
    

Intervention name(s): COVID19 vaccine; Saline
Intervention type(s): Biological; Biological
Intervention description(s): COVID19 recombinant spike protein with Advax-SM adjuvant; Saline control
Other intervention name(s): COVAX-19 vaccine; Saline control
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomised controlled study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: COVID19; coronavirus; vaccine; adjuvant