Vaccines beyond COVID: Onto the fight against malaria

Vaccines beyond COVID

Cosmos Magazine


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By Cosmos

The power of vaccination has been front and centre over the past few years, lighting a way for the planet through the pandemic. But immunisation isn’t just a COVID-19 issue: it’s a collective movement that helps fortify the global population against a whole host of diseases.

Doing it in a way that’s careful and safe is essential. While the urgency for vaccinations to protect against deadly ailments such as malaria and HIV is as serious as ever, breakthroughs don’t happen overnight. Not only is research rigid, but clinical testing is as cautious and rigorous as can be – ensuring that every vaccine that reaches the public is unimpeachable in its safety.

What can happen much faster is policy changes that ease the way for vaccine development and access. Governments in countries such as India have shown the power of investing in vaccine manufacturing and development, while global initiatives to promote equitable access to immunisation have been undercut by parties seeking profit and power.

In the dreamed-of realm beyond the pandemic, countries around the world will need to protect their populations from established and emerging viruses and diseases. Striking a balance between the science and policy will be vital as the pall of COVID lifts and the threat of new pathogens appear.

In this immunisation special, published in partnership with 360info, we look first at the remarkable steps forward in vaccine development in India, and conclude with the lessons learnt from COVID and COVAX – the global program designed to improve access to vaccines.

Paving the way for a global malaria vaccine

Malaria is a huge public health problem in India, but relief could be on the way if the early promise of vaccines in development is fulfilled.

Malaria remains a deadly disease around the world, primarily affecting children below the age of five. Africa bears the brunt of malaria cases – more than 90% of the world total in 2019. In southeast Asia, India accounts for 80% of the region’s malaria burden. However, the nation’s investment and support for control and elimination programs is beginning to pay off, as India’s vaccine research and development offers signs of hope.

Malaria parasites have a complex life cycle and we still don’t fully understand the immune response to infection – but  we know that people who are repeatedly exposed to malaria develop immunity to the disease. Because malaria immunity can be acquired, it suggests a malaria vaccine would be possible.

Because malaria immunity can be acquired, it suggests a malaria vaccine would be possible.

But the complexity of the malaria parasite makes developing a vaccine against any stage of it a formidable challenge. Injecting irradiated sporozoites (an early stage of the parasite that infects liver cells) or transferring antibodies from malaria-immune adults can protect others from infection.

RTS,S — also known as Mosquirix — is the world’s first WHO-approved vaccine against the type of malaria caused by the Plasmodium falciparum parasite. The vaccine is based on a protein expressed on the surface of sporozoite, called circumsporozoite protein (CSP).

The vaccine is being evaluated in the Malaria Vaccine Implementation Programme (MVIP) in Ghana, Kenya and Malawi. Ongoing studies have shown that it reduces deadly malaria by about 30%. Based on this, the WHO has recognised Mosquirix as a potentially complementary tool to fight malaria globally. In 2021, WHO recommended widespread use of Mosquirix, particularly among children in sub-Saharan Africa and other regions with moderate to high malaria transmission.

Vaccine malaria
October 08, 2021 World Health Organization backed the widespread rollout of the Mosquirix vaccine. Nairobi, Kenya. Credit: Getty Images / Stringer / Getty News

While Mosquirix’s development is impressive, it still falls short of the WHO’s own benchmark for malaria vaccine efficacy of 75%. Second-generation vaccines are now in development, including a highly promising vaccine similar to Mosquirix named “R21/Matrix-M”.

All vaccines undergo a rigorous process of clinical trials in three phases. Whether vaccines are safe and trigger an immunological response in humans is tested in Phase 1a/1b trials. Whether the vaccine is effective at protecting against the disease is tested in Phase 2a/2b. Finally, a big Phase 3 field trial is undertaken to monitor safety, potential side effects and evaluate the vaccine’s efficacy on a large scale to ensure the vaccine works under varied conditions, including different malaria-transmission patterns.

It usually takes 10–15 years to complete a malaria vaccine clinical trial

One phase 2 clinical trial – R21/Matrix-M in children – met the WHO-specified efficacy goal of at least 75% over 12 months. Phase 3 of the trial is underway for children aged between 36 months and five and in four African countries.

Also in development are vaccines that aim to block malaria’s spread by preventing parasite growth in blood and prevent clinical illness and parasite transmission from humans to mosquitoes.

Blood-stage vaccines have made much less progress, with only a handful of candidates evaluated in Phase 2 clinical trials, underlining the challenges of generating an effective vaccine against the pathogenic blood-stage malaria infection. Although transmission blocking vaccines do not offer direct protection, blocking malaria transmission is an essential component of effective control and elimination strategies. Progress is slow, with one candidate showing promise in early clinical trials, and a Phase 2 clinical trial ongoing in Mali.


  • The first successful vaccine was for smallpox, introduced by British physician and scientist Edward Jenner in 1796.
  • Prior to COVID-19, the fastest vaccine to go from development to deployment was the mumps vaccine (MMR) in the 1960s, which took about four years.
  • Only 19 vaccine introductions were reported in 2020 – less than half of any year in the preceding two decades.
  • Vaccines save an estimated 2–3 million children each year from deadly diseases. However, in the same period, approximately 1.5 million children under five lose their lives to vaccine-preventable diseases.

India is an important player in these vaccine innovations. Hyderabad-based pharmaceutical company Bharat Biotech has a licence from vaccine developers GlaxoSmithKline to manufacture Mosquirix. By 2029, Bharat Biotech is expected to be the sole global manufacturer of the vaccine.

The Serum Institute of India (SII), the world’s largest manufacturer of vaccines, holds the licence to manufacture the second-generation malaria vaccine R21/Matrix-M. Along with Novavax AB from Sweden, the SII is collaborating with Oxford University’s Jenner Institute for Phase 3 clinical trials of the vaccine.

Vaccine malaria
Travelling healthcare worker administers a dose of Covishield, a coronavirus vaccine manufactured by Serum Institute of India. Credit: Pacific Press / Contributor / Getty

Scientists at the New Delhi-based International Centre for Genetic Engineering and  Biotechnology (ICGEB) have completed the first-ever Phase 1 clinical trial of a P. falciparum malaria vaccine, produced by indigenous recombinant technologies. India also produced an experimental vaccine against a different malaria-causing pathogen, P. vivax, which was successfully evaluated in a Phase 1 trial. A Phase 2a trial, with controlled human malaria infection, is being planned at Oxford University, then later in Thailand.

Vaccine malaria
BMC medical staff conducts Swab Test, Rapid Integen Test and malaria test of Police personnel. Mumbai, India, 2020. Credit: Hindustan Times / Contributor / Getty

Controlled human malaria infection studies have the potential to fast-track initial evaluations of vaccine efficacy and can help conduct first trials of vaccines that rely on fewer adult subjects. Controlled human malaria infection has also been increasingly implemented in places where malaria is endemic. It’s critically important to understand dynamics between vaccine-induced immunity and pre-existing immunity during ongoing natural exposure to the disease.

Many countries – including the USA, UK, Germany, Australia, Kenya and Thailand – have developed the capacity to do controlled human malaria infection studies. India has all the infrastructure in place to do the same, but is yet to make a model available for malaria researchers. Doing so could accelerate the development of candidate vaccines to fight malaria and other diseases.

Vaccine research and development is a time-consuming process that requires extensive governmental and non-governmental support. In India, a lot of local research is underway to develop new vaccines against several deadly diseases, including dengue, chikungunya, cholera, and shigella, as well as malaria. With substantial investment from the Indian government, these initiatives could pave the way for the creation of globally beneficial vaccines.

How lessons from COVAX could help global vaccine equity

COVAX was supposed to be the elixir for vaccine inequality – it wasn’t. But it adds to the lessons taken from previous global experiences to help make progress.

Most early deaths caused by COVID-19 happened in developing economies. The global scale of the pandemic eventually made clear where most vaccines are distributed and who bears the disproportionate health burden due to not having access to them.

Low-income economies, clearly, were the most disadvantaged.

Vaccine manufacturers have been heavily criticised in some quarters for prioritising profit over making access to vaccines equitable – by retaining high-profit margins, holding on to intellectual property rights and production rights, and prioritising ‘those who can pay most’.

Criticism of ‘pandemic profit’ is particularly directed at those who make mRNA vaccines, a relatively new and promising vaccine technology. Meanwhile, the term ‘vaccine nationalism’ was used to describe how countries – especially developed ones – saved large amounts of vaccine doses for their own population, limiting access to doses for low-income economies.

To improve international vaccine equity, the COVID-19 Vaccine Global Access mechanism (COVAX) was developed, co-led by the World Health Organisation (WHO), vaccine alliance Gavi, and the Coalition For Epidemic Preparedness Innovations (CEPI).

COVAX is designed to be a global pool of funds that serves as a procurement mechanism. Backed by donors and high-income economies, the goal is to make COVAX the most attractive customer bidding for vaccines, with the bargaining power to negotiate pricing and enter advanced purchase agreements with manufacturers.

In reality, COVAX is plagued by complex political power imbalances between the countries in need, developed economies and the private sector. For example, the so-called self-financing countries that helped finance COVAX had – in many cases – already struck purchasing deals with vaccine manufacturers before COVAX amassed enough buying power to secure doses at scale for developing economies.

Donor countries failing to honour their pledge to ‘dose share’, lagging on their deliveries, earmarking donations, or donating on an ad hoc basis, all caused delays. This meant only a small proportion of pledged doses were delivered and many near-expired doses wound up being dumped as ‘donations’.

Meanwhile, manufacturers have not donated any pledged vaccine doses to COVAX and shifted instead to selling doses ‘at cost’ through commercial deals.

Work is underway to develop domestic capacities in developing economies that will reduce dependence on more powerful countries. Tech-transfer can play an important role in expanding the vaccine manufacturing capacity in developing economies, improving access and lessening donor dependency.

In June 2021, the WHO announced a partnership with a South African consortium to establish a multilateral technology transfer hub for mRNA vaccines for COVID-19 and other diseases. The consortium, Afrigen Biologics and Vaccines, will manufacture the mRNA vaccines themselves and train up another manufacturer. An additional 10 countries will receive tech transfer from the WHO for mRNA vaccines – Indonesia, Bangladesh, Pakistan, Serbia, Vietnam, Tunisia, Kenya, Egypt, Nigeria, and Senegal.

Important elements for vaccine production are the transfer of the technological know-how and relevant clinical data, human resource training and capacity building, and addressing the issue of intellectual property rights.

Another partner for the tech-transfer hubs, the Medicines Patent Pool, has stated that “technology used in the hub is either not covered by patents or that licences and/or commitments-not-to-enforce are in place to enable freedom to operate” via “voluntary participation of intellectual property holders”.

There is still concern from experts that the reluctance of mRNA vaccine manufacturers to fully abandon their intellectual property rights will significantly undermine the hub’s activities and its sustainability.

The innovative financing mechanism tried by COVAX – and the challenges it faced – raises a critical issue for technology transfer sites in developing economies: how to find and sustain financing.

The methods and materials used in mRNA technology are still relatively expensive, challenging the potential for scalability and cost-effectiveness. The upfront total cost to produce 100 million doses of mRNA vaccines annually is between US$127 million and US$270 million (AU$178–379 million), according to modelling.

One widely cited as successful example of innovative vaccine financing is the International Finance Facility for Immunisation (IFFIm). The facility issues ‘vaccine bonds’ to investors, mostly based in developed economies, mobilising the funds to frontload the immunisation of children in developing economies with secondary support from government donors.

Important elements for vaccine production are the transfer of the technological know-how and relevant clinical data, human resource training and capacity building, and addressing the issue of intellectual property rights.

The IFFIm has helped deliver vaccines to children who would have otherwise missed out – but its model has issues. Its complex relationship between the development sector and the private capital market has transferred a significant amount of profit to the private actors involved in the form of costly transaction fees, intermediary fees, or interest with financial risks backed up by public money.

Health interventions that can save many lives, such as vaccines, should be accessible to everyone at the time they need them – especially those who are most vulnerable. Many approaches have been taken to make vaccine equity a reality, from ethical-based pledged agreements to market and tech-based solutions.

But the pandemic and issues around vaccine access show the right mix is needed to solve a highly complicated problem in which political and commercial interests intersect with a need to save as many lives as possible.

Immunisation special writers:

Introduction: Reece Hooker is an editor at 360info.

Malaria vaccines: Dr Paushali Mukherjee is an immunologist and Program Manager at the Multi Vaccines Development Program (MVDP), in India; Professor Virander S Chauhan is President of the governing board of MVDP.

Lessons from COVAX: Dr Putri Widi Saraswati is an Indonesian public health specialist and medical doctor. He’s currently a research intern at the UN University-International Institute for Global Health (UNU-IIGH), the UN think tank on global health.

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