Malaria Vaccine Project Update, Australia

MALARIA VACCINE PROJECT UPDATE

Since the last newsletter, World Malaria Day was marked on the 25th April. This is an internationally recognised day that highlights global efforts to control malaria, the need for continued investment and political commitment and to celebrate our achievements. Since 2000, the world has made historic progress against malaria resulting in hundreds of millions of clinical cases averted and millions of lives saved. We must remember however, that half of the world’s population still live in regions where they are at risk of contracting malaria and this dreadful disease takes a child’s life every two minutes. No single preventive measure will be solely responsible for eradicating the malaria parasite. A combination of strategies will be needed, including we hope, a highly effective malaria vaccine.

The majority of malaria vaccine candidates in development are “sub-unit” vaccine candidates that contain only a small part of the parasite, often just a single protein. Unfortunately, many of the parasite proteins that have been tested as a malaria vaccine are highly variable, so the vaccine really only protects against parasite strains that match the vaccine. This is similar to what we see with the annual influenza vaccine. As there are thousands of different parasite strains circulating in the field, some of which do not match, these vaccines have not shown high levels of effectiveness.

Our laboratory is working on a different type of vaccine approach that includes the whole parasite in the vaccine. This means that all parasite proteins are in the vaccine, including those that are invariant (the same) between different parasite strains. We believe this will result in an immune response that is broadly protective against the many different
circulating parasite strains. We are one of the only research groups in the world working on a whole parasite vaccine that targets the blood-stage of the malaria parasite. It is the parasite’s blood-stage that is responsible for the clinical disease associated with malaria infection and is also able to infect the mosquito vector.

Laboratory studies focused on our whole blood-stage parasite field-deployable malaria vaccine are continuing to show promising results and the plans for a Phase I trial of this vaccine in 2022 are progressing well. In the coming weeks, we anticipate submitting a manuscript describing the evaluation of our field-deployable vaccine formulation in pre-clinical studies. These studies included extensive optimisation to maximise vaccine efficacy and identifying which parts of the vaccine-stimulated immune response are critical for killing the malaria parasite.

We are also concluding the immunological studies from our recently completed trial for our chemically attenuated Plasmodium falciparum whole parasite blood-stage vaccine candidate. This study involved administering 3 doses of the vaccine to malaria-naïve volunteers and then infecting them with malaria parasites to see if the vaccine was protective. Although we are now focusing on a next-generation field-deployable vaccine formulation, this study represents the first time that the effectiveness of a whole parasite blood-stage vaccine candidate has been evaluated in humans. We look forward to submitting this manuscript late in the second half of 2021 as it provides proof-of-concept for a whole parasite blood-stage malaria vaccine approach in humans. This clinical study and our future Phase I trial next year have really been made possible through the contributions of Rotary and Rotarians. We are truly inspired by their passion and commitment to help rid the world of this devastating disease.

Recently, the World Health Organisation (WHO) highlighted that the progress in controlling malaria has levelled off in many of the countries that are hardest hit by this disease. At the same time, it is encouraging to know that there are a number of countries with low levels of malaria that have been moving towards the target of “zero malaria”.

Since 2017, the WHO has supported a group of 21 countries across 5 regions through a special initiative known as “E-2020”. Their common goal was to eliminate malaria by 2020. To reach the elimination milestone, a country that was malaria endemic in 2015 had to achieve at least one year of zero indigenous cases and then maintain this through until the end of 2020. Indigenous cases of malaria are those acquired by mosquito transmission in an area where malaria regularly occurs whereas introduced cases of malaria are acquired by mosquito transmission from an imported case in an area where malaria does not regularly occur.

Seven E-2020 member countries succeeded in reaching this milestone: Algeria, Belize, Cabo Verde, China, El Salvador, the Islamic Republic of Iran and Malaysia. Note: Malaysia is a special case because although malaria species transmitted between people have been eliminated, the Plasmodium knowlesi malaria parasite, normally found in monkeys, continues to infect people. Three countries who were not part of the E-2020 initiative also reached this milestone: Azerbaijan, Sri Lanka and Tajikistan.

Common drivers of successful malaria elimination included: political commitment to ending the disease, engagement of communities and free primary health care ensuring that all people in need of malaria-related health services could access them without financial hardship.

How does a country obtain the WHO’s malaria-free status? Certification of malaria elimination is granted when a country proves beyond reasonable doubt that indigenous malaria transmission by mosquitoes has been interrupted nationwide for at least the past 3 consecutive years. A country must also be able to demonstrate the capacity to prevent the re-establishment of transmission of the malaria parasite. A national surveillance system that is able to rapidly detect and respond to any malaria cases must be operational, together with measures to prevent local outbreaks due to any imported
cases of the disease.

The final decision on awarding malaria-free certification rests with the WHO Director-General, based on a recommendation by the Malaria Elimination Certification Panel. A total of 39 countries and territories have been certified malaria-free.

While this is great progress, it is important that countries that have eliminated malaria do not become complacent. Once people develop immunity against malaria, they have to be continually exposed to the malaria parasite to keep this immunity. Much in the same way you need booster shots for vaccines. Once malaria is eliminated and people are no longer exposed to the malaria parasite, they will begin to lose their immunity. If indigenous malaria transmission does reoccur, they may be at greater risk of developing severe and fatal malaria than they were before.

This resurgence of malaria has been seen before in countries that had eliminated/nearly eliminated the malaria parasite. It can happen for many reasons, but most recently it has been seen due to COVID-19-related disruptions to malaria preventive measures e.g. spraying of insecticides, malaria diagnosis and treatment services and provision of bed nets. Timor Leste, a country that reported zero indigenous cases of malaria in 2018-19, saw an outbreak of the disease along its shared border with Indonesia in 2020.

The malaria parasite is extremely clever and that is why it has been with us for millennia. The continuing development of resistance by the malaria parasite to currently used anti-malarial drugs and by the mosquito to vector control interventions, highlight how fragile our progress against the malaria parasite is. It also highlights why we need multiple tools to fight malaria. No single preventive measure in our toolbox will likely be responsible for parasite eradication. We also need to add new tools, such as a highly effective malaria vaccine, to continue parasite elimination, prevent parasite resurgence in malaria-free areas and progress towards global eradication.

* Taken from: “Zeroing in on malaria elimination: final report of the E-2020 initiative.” https://www.who.int/publications/i/item/9789240024359

Dr Danielle Stanisic
Associate Research Leader