History, facts and future

mRNA vaccine technology is a field full of promise – as well as unanswered questions – for communities living with the burden of the world’s deadliest infectious diseases.

Despite appearances, mRNA technology is not new. But since mRNA vaccines burst onto the world stage to tackle COVID-19, a host of possibilities have opened up as research teams explore ways to harness mRNA technology to address other global health issues.

The infectious diseases of the “big three”

Tuberculosis, malaria and HIV are known as the “big three” infectious diseases: they are the deadliest communicable diseases in the world. Together, they killed more than 2.8 million people in 2020, according to figures from the World Health Organization (WHO). Initial data suggests there were 1.8 million deaths from COVID-19 in 2020, although the WHO estimates that number could be “at least” 3 million.

Beyond the deaths caused by the Big Three, nearly 290 million people were living with HIV, malaria or tuberculosis in 2020. These conditions are known as the diseases of poverty. They disproportionately affect developing countries and are both the result and the cause of poverty.

A total of 1.5 million people died from TB in 2020. Globally, it is the second infectious killer after COVID-19. An estimated 10 million people fell ill with TB in 2020 – 5.6 million men, 3.3 million women and 1.1 million children. Only eight countries accounted for two-thirds of the total number of TB cases: India has the highest burden, followed by China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh and India. South Africa.

Around 627,000 people died of malaria in 2020, with around 241 million cases reported worldwide. Africa bears the majority of the global burden of malaria – 95% of malaria cases and 96% of malaria deaths. About 80% of malaria cases in this region were in children under five.

Meanwhile, in 2020, 680,000 people died from HIV-related causes. There were 1.5 million new cases of HIV in 2020, while globally an estimated 37.7 million people are living with HIV. The majority of people living with the virus – 25.4 million – are in Africa.

History of messenger ribonucleic acids

mRNA technology has been in development since the 1960s, but proved reactive when SARS-CoV-2 hit the world. Its success in battling COVID-19 has sparked renewed interest in developing the technology for other diseases.

In a nutshell, mRNAs are messenger ribonucleic acids that trigger an immune response from cells before degrading. They work by introducing a coded sequence for a disease-specific antigen – a substance that causes the body to make antibodies against it; once this antigen is produced in the body, the immune system can recognize it and prepare to fight the real virus, bacteria or parasite.

Prior to the COVID-19 pandemic, exploration of mRNA vaccines for a range of diseases had begun, including Ebola, Zika and rabies, as well as cancers and influenza.

But the field has grown rapidly in recent years. In a 2018 review, US scientists said mRNA vaccines represent a promising alternative to conventional vaccine approaches due to their high potency, rapid development capability, and potential for low-cost manufacturing and administration. safe.

“The field of mRNA vaccines is developing extremely rapidly; a large amount of preclinical data has accumulated over the past few years and several human clinical trials have been initiated,” the scientists said. “The data suggests that mRNA vaccines have the potential to solve many challenges in developing vaccines for infectious diseases and cancer.”

Why is mRNA technology so exciting?

Interest in mRNA technology has exploded since it entered the mainstream during the COVID-19 pandemic. The full text of a 2020 review of mRNA technology by researchers in Shanghai and Beijing has been viewed approximately 35,000 times and has over 40 citations, giving it a high impact factor in the world of scientific literature.

mRNA vaccines show promise due to the speed with which they can be developed and produced, as well as their flexibility and adaptability to variants. American pharmaceutical company Moderna’s mRNA vaccine against SARS-CoV-2 began clinical trials 63 days after the virus’s genome was published. By comparison, the human papillomavirus (HPV) vaccine Gardasil – which uses recombinant DNA technology – took 15 years to be approved for use, in 2006.

Developments in the stability of mRNA vaccines have led to a massive increase in interest in the technology. mRNA vaccines were tested in the early 1990s, but the scale of production and their fragile stability raised concerns, according to a 2019 study.

With advances in synthetic mRNA production, the technology has become more attractive. Other forms of safe and effective vaccines carry a weakened virus or part of the virus, and increasing the volume of pathogens needed to produce large-scale immunizations, then weakening the virus, takes time.

With the Coalition for Epidemic Preparedness Innovations (CEPI) setting the task for the world to generate vaccines within 100 days of the identification of a new germ, research and development groups – including a team from the University of Oxford who produced a 100-day pre-print blueprint for the vaccine – say they are up to the challenge.

The future of mRNA vaccine technology

In the first months of 2022, there has been a flurry of activity around the transfer and development of mRNA technologies, with the WHO announcing additional locations for its mRNA vaccine technology transfer centers, and the German biotechnology company BioNTech designating sites for new production facilities in Africa.

Amid these announcements, world health leaders and scientists have repeatedly highlighted mRNA’s potential to tackle the big three diseases, as well as non-communicable health conditions such as cancer.

And clinical trials have already started, or are expected to start this year, for mRNA vaccine candidates against HIV, malaria and tuberculosis.

But scientists temper their optimism with caution, as reaching the stage of clinical trials does not always guarantee that a candidate vaccine will be proven safe and effective. And global health advocates say funding for vaccine research and development, and a continued focus on technology transfer and knowledge building in countries in the Global South, must continue.

Recipes for COVID-19 mRNA vaccines have been tightly held by pharmaceutical companies, which refuse to share patents with developing countries. To combat “vaccine hoarding” and global health inequities, the WHO and a consortium of research organizations and the Medicines Patent Pool came together in 2021 to unlock the structure of mRNA vaccines, establishing the first mRNA research center and transfer center in South Africa, with ‘spokes’ in Brazil and Argentina.

In February, the WHO announced that six additional countries in sub-Saharan and North Africa would receive technology to enable them to manufacture COVID-19 vaccines under the initiative.

The WHO said mRNA technology could also be used for insulin to treat diabetes, cancer drugs and, potentially, vaccines against the three big deadly infectious diseases. Ultimately, the WHO said, mRNA technology transfer centers will promote access to vaccines for all, strengthen health security and promote self-reliance for the future.

Kate Stegeman, Africa region advocacy coordinator for Doctors Without Borders (MSF) Access Campaign, said diversifying mRNA vaccine manufacturing capacity to low- and middle-income countries should be a priority. global health. She said: “More regions producing mRNA vaccines as an essential preparation against infectious diseases could strengthen the response not only to COVID-19 and future infectious diseases, but also potentially to existing diseases such as malaria, tuberculosis and HIV.”