Vaxine has a long history of coronavirus vaccine development supported by almost two decades of competitive research funding from the US National Institutes of Health.
On July 2, 2020, Vaxine’s recombinant protein-based vaccine became the first Covid-19 vaccine developed in the Southern hemisphere to enter human trials. Based on positive results it subsequently progressed into Phase 2, and then Phase 3, clinical trials.
The Phase 3 trial in Iran that included 16,876 participants met its primary efficacy endpoint by demonstrating greater than 60% protection against infection by the challenging Delta variant.
In early October 2021, COVID-19 received emergency use authorisation from the Iranian FDA, thereby making it the first recombinant full spike protein vaccine to receive approval anywhere in the world. It thereby beat protein vaccines under development by Novavax and Sanofi to this important milestone.
Already, 2 million doses of COVID-19 vaccine have been safely distributed, with no cases of vaccine-associated anaphylaxis, myocarditis or clotting disorders seen.
In clinical trial subjects, COVID-19 vaccine induced antibodies able to neutralise the major variants of concern including Alpha, Beta, Gamma, Delta, Lambda, with assays for Omicron under development.
This broad protection has been confirmed in animal challenge studies where Spikogen protected against infection with ancestral, Beta, and Delta variants.
Notably, it also inhibited nasal virus shedding and prevented transmission of the infection to naive co-housed animals.
Vaxine is currently planning the next stages of development of its successful Covid-19 vaccine.
This will address the optimal interval between vaccine doses, efficacy in children, use as a booster dose after other vaccines, and providing optimal protection against Omicron, durability of protection over time and ability to inhibit transmission.
Seasonal influenza continues to be a major public health burden, causing an estimated 300,000 – 600,000 deaths globally each year.
Whilst useful in reducing this burden of disease, current influenza vaccines have room for improvement as they remain only partially effective, need to be administered every 12 months, and regularly need to be changed to accommodate changes in the nature of circulating influenza viruses.
One method to make influenza vaccines more effective is to add an adjuvant and Vaxine has shown in clinical studies that its Advax adjuvant can enhance the effectiveness of seasonal influenza vaccines.
In addition, Vaxine is working with its partner Protein Sciences Corporation, a company recently acquired by Sanofi Pasteur on vaccines to protect against influenza pandemics caused by bird flu viruses.
Finally, Vaxine is developing its own universal influenza vaccine candidate based on targeting the influenza M2 protein.
Respiratory Syncytial virus is the second most common cause of serious viral respiratory disease after influenza. Young children are particularly susceptible and present with bronchiolitis and breathing difficulties.
RSV pneumonia is also a common cause of acute respiratory disease in the elderly. There is currently no approved vaccine against RSV, although a therapeutic antibody is approved for use in very young children presenting with RSV.
Together with partners at University of Pittsburgh and a US company, Vaxine has been developing a new RSV vaccine that combines a prefusion f protein of RSV with Advax adjuvant. This vaccine has proved successful in prevention of RSV disease in immunised mice, and cotton rats, with the next step being to test its safety and effectiveness in human subjects.
Hepatitis B (HBV) is the world’s most common liver infection and can lead to cirrhosis and liver cancer. It is transmitted through blood contact, unprotected sex, re-used needles or delivery of a newborn baby from an infected mother.
A significant number of infected adults develop chronic infections, as do most infected babies and children since they are much less able to get rid of the virus. According to the WHO fact sheet, two billion people (1 out of 3) in the world have been infected with the HBV virus at some time and 350 million people are chronic carriers of the virus.
Approximately one million people in the world die from liver failure each year as a result of HBV and five thousand die from this virus in Australia each year. In regions of Africa and Asia, up to 10% of the general population have become chronically infected with the virus, while in developed countries such as USA and Australia less than 1% of the population is chronically infected.
Because of the severity of HBV, the WHO called in 1991 for all countries to add HBV vaccine to their national immunization programs. By 2002, over 120 countries had added HBV vaccine to their national programs.
The currently available HBV vaccine is at least 90-95% effective at preventing HBV infection and is a combination of a protein from the HBV virus plus an aluminium hydroxide adjuvant. It is necessary to add the aluminium hydroxide adjuvant because the protein on itself does not stimulate a powerful enough immune response to provide adequate protection.
Vaxine has developed a more potent HBV vaccine that in animal studies has shown potential to suppress HBV virus in already infected individuals. This vaccine has already been shown to be safe and effective in healthy human volunteers and next will be tested in subjects with chronic HBV infection.
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that can cause fatal encephalitis in humans and horses. Other related viruses of the JE-serotype family are Murray Valley encephalitis (MVEV), Kunjin and West Nile virus (WNV).
These viruses are widely distributed in Asia and in the past decades JEV has spread into the Asia-Pacific region. Wide-spread virus activity has been detected in Indonesia, PNG and across the Torres Strait Islands of northern Australia with the ongoing risk that JEV will become established as a cause of serious human disease on the Australian mainland.
JE is the leading cause viral encephalitis in Asia, where 2-3 billion people are at risk of contracting the disease. Annually, ~50,000 cases of JE are reported, resulting in ~10,000 deaths and a high incidence of neuropsychiatric deficits among survivors.
The disease is caused by JEV, an enveloped, positive-strand RNA virus belonging to the family, Flaviviridae (genus Flavivirus). Clinical manifestations of JE vary and may include fever, headache, a change in mental status, seizures, tremors, and generalised paresis.
Vaccination is the most effective means for preventing encephalitis due to JEV but no vaccine is available against the other JE-serotype viruses.
Vaxine has successfully developed a novel JEV vaccine that in animal models is not only highly potent against JEV but is the first flavivirus vaccine demonstrated to elicit cross-protective immunity against MVEV, Kunjin and WNV. This provides Vaxine with the opportunity to develop the first prophylactic vaccine against encephalitis caused by multiple different flaviviruses.
Malaria remains a major global health issue, affecting hundreds of millions of individuals globally. Despite many decades of research, a highly effective malaria vaccine remains elusive, although GSK’s RTS-S vaccine containing their AS01 combination adjuvant has shown a low level of short term protection, showing that a better vaccine should be feasible.
Vaxine has been collaborating with Leidos and USAID to help develop an effective malaria vaccine formulated with Vaxine’sAdvax adjuvant platform.
Ebola is one of the world’s most lethal viral infections, with a mortality rate of greater than 80% amongst infected individuals.
Vaxine has been collaborating with USAMRIID, the medical division of the US army to develop an Ebola vaccine based on the combination of USAMRIID’s viral like particle technology with Vaxine’sAdvax adjuvants.
This vaccine has been shown to be highly effective in protecting against lethal Ebola infection in infected animals, even after just a single vaccine dose
Tuberculous remains a major cause of lung disease particularly in developing countries but is also a problem in individuals with immune-deficiency including those suffering from HIV infection.
Although a live attenuated vaccine, BCG, is available it is only protective in young children and its protective effects rapidly wane.
Vaxine is collaborating with University of Sydney to develop a recombinant protein vaccine against tuberculosis combined with Vaxine’sAdvax adjuvant platform. This vaccine has been shown to provide protection in animal models and the next step will be to produce the recombinant protein under GMP in order to undertake Phase 1 clinical trials.
Although naturally occurring human anthrax infection has become uncommon, concern over the use of anthrax as a biological weapon of mass destruction and remains at high levels. The anthrax attacks perpetrated against the American population in 2001 were reminders of the deadliness of the disease and the ease with which the spores could be disseminated.
Modeling studies exploring the use of anthrax when employed on a larger offensive scale are even more sobering. The World Health Organization has estimated that 50 kg of B. anthracis released upwind of a population center of 500,000 would result in up to 95,000 deaths, with a further 125,000 incapacitated.
The pathogenesis of anthrax relates largely to its virulence factors, the most important of which are its secreted exotoxins lethal factor (LF) and edema factor (EF), both of which require PA binding to function.
Previous efficacy studies in animal models have demonstrated that PA must be present in nonliving anthrax vaccines and to date, all human vaccines developed against anthrax are comprised largely of PA.
AVA is the only licensed anthrax vaccine in the US. This vaccine was first developed in the 1960s and is derived from the filtrate of a toxigenic nonencapsulated strain of B. anthracis. The filtrate contains a mixture of cellular products, the most important of which is PA (35% or more).
The vaccine is adsorbed to aluminum hydroxide adjuvant, and contains formaldehyde and benzethonium chloride as preservatives. The amount of PA, as well as other vaccine components, is known to vary considerably between vaccine lots, with subsequent potential impact on protective efficacy and reactogenicity.
The vaccine has traditionally been administered subcutaneously as a series of 6 vaccinations over 18 months, with annual booster vaccinations thereafter to maintain immunity.
Vaxine and its collaborators have shown that formulation of a recombinant protective antigen (rPA) with Advax adjuvant enabled even single dose protection of immunized animals against an aerosol anthrax challenge. These promising results await translation into larger animal models and human clinical trials, contingent upon this program receiving external funding.
After almost 40 years of intensive research, there have been considerable breakthroughs in understanding the nature of the HIV virus, but nevertheless a preventative vaccine remains elusive.
Vaxine has teamed up with Advanced Bioscience Laboratories in Rockville, MA, to develop a novel HIV vaccine based on a prime boost strategy where individuals are first primed with a DNA vaccine and then boosted both intranasally and intramuscularly with a recombinant protein vaccine formulated with Vaxine's Advax adjuvants.
This strategy has been shown effective in inducing both humoral and cellular systemic and mucosal immunity in both small animal and nonhuman primate models, and the NIH are currently supporting ongoing NHP studies to further validate this approach in the lead up to planned human clinical trials.
Currently the only solution for people who suffer from serious life threatening insect bite allergies, such as bee or ant venom allergy, is to carry an Epipen or to undertake long term frequent injections of venom to induce desensitisation.
Vaxine has been collaborating with local allergists to undertake clinical trials to assess whether addition of Advax adjuvant to current desensitisation therapies might make them more effective thereby reducing the need for such frequent or long-term injections.
Vaxine is working on a number of different complementary cancer immunotherapy approaches.
Firstly, it has developed an autologous cancer vaccine that is made from the patient’s own tumour and is designed to induce T cells to kill the patient’s tumour.
Secondly, Vaxine has developed a number of potent innate immune activators (toll-like receptor agonists) that can be injected directly into a patients tumour, and thereby help activate T cells in the tumour to attack it.
Both these therapies can be used together and further combined with immune checkpoint inhibitors or traditional chemotherapy. Animal studies have already confirmed the effectiveness of these anti-tumour therapies and it is anticipated that human clinical trials will commence before the end of 2018.
Shigellosis is an intestinal disease characterised by bloody diarrhoea, caused by bacteria known as shigella. Children under age 5 are most likely to get shigella infection, but it can occur at any age.
Shigella is one of the leading bacterial causes of diarrhoea worldwide, causing an estimated 80–165 million cases and several hundred thousand deaths, particularly in young children in developing countries.
Whilst numerous attempts have been made to develop an effective vaccine against shigella, to date, these have not been sufficiently successful to lead to an approved vaccine.
Challenge and re-exposure trials with Shigella suggest the incidence of disease decreases following previous Shigella infections, suggesting a vaccine should be feasible.
Immunity to Shigella appears to be largely strain-specific, so a vaccine to cover the most common strains of S. flexneri and S. sonnei would need to be cross-protective. A further problem with developing an effective shigella vaccine sis the lack of good animal models on which to test candidate vaccines. Furthermore, a shigella vaccine does not have strong commercial drivers as most potential clients are in developing countries.
Despite these challenges Vaxine scientists remain committed to developing an effective shigella vaccine based on a recombinant protein approach. This vaccine when combined with Vaxine's unique Advax adjuvant has shown some protection in small animal challenge models, and we remain hopeful that it might one day be able to be advanced into clinical development, although this would require significant resources and hence could only be achieved if Vaxine can find the right partner to help with this program
Opioid addition is a growing problem globally. One potential strategy to counter this problem is to develop an opioid vaccine.
Vaxine has been collaborating with academic groups attempting to develop an opioid vaccine, with studies currently underway in mice and monkeys to assess the ability of Vaxine’s Advax adjuvant to increase the effectiveness of these vaccines.
Alzheimer’s disease is a growing global issue with the ageing of global populations. Currently there is no way to prevent Alzheimer’s and although several drugs are approved for therapy these have relatively weak effects.
Vaxine has been collaborating with the Institute of Molecular Medicine in California to develop an Alzheimer’s vaccine based on the combination of a recombinant protein with Vaxine’s Advax adjuvant platform.
This vaccine has been shown to be highly effective in preventing Alzheimer’s in animal models, with the next step being to conduct human clinical trials.
Zika is a flavi-virus that has recently been shown to cause foetal malformations if pregnant women become infected.
Vaxine is collaborating with Protein Sciences to develop a vaccine based on a recombinant Zika protein plus Vaxine’s Advax adjuvant platform.
This vaccine has been shown in animal models to induce high levels of neutralising antibodies that provide strong protection against Zika infection.
One possibility being explored by Vaxine is to combine this with its other flavi-virus vaccines in order to make a single vaccine that protects against a wide range of flavi-viruses including JEV, MVEV, WNV and Zika.
Typhoid fever remains endemic in many parts of the developing world and still kills many young children.
Although typhoid fever vaccines are available, these provide only short lived protection and hence need to administered regularly to maintain immunity.
Vaxine is collaborating with Boston company, Matrivax Inc, to develop a typhoid fever vaccine including Vaxine’s Advax adjuvant platform, that is able to provide stronger and longer lasting protection extending for at least 10 years.