History, facts and future

mRNA vaccine technology is an area full of promise – as well as unanswered questions – for societies living under the world’s deadliest infectious disease burden.

Despite appearances, mRNA technology is not new. But since mRNA vaccines have emerged on the global stage to tackle COVID-19, a wealth of possibilities have opened up as research teams explore ways to harness mRNA technology to address other global health concerns.

Infectious diseases ‘Big Three’

Tuberculosis, malaria, and HIV are known as the “big three” infectious diseases: they are the world’s deadliest infectious diseases. Together, they killed more than 2.8 million people in 2020, according to World Health Organization figures. Preliminary data suggest there will be 1.8 million deaths from COVID-19 in 2020, although the World Health Organization estimates the number could be “at least” 3 million.

In addition to 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 diseases of poverty. They disproportionately affect developing countries, and are both a consequence and a cause of poverty.

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

About 627,000 people died of malaria in 2020, with 241 million cases reported worldwide. Africa bears the majority of the world’s malaria burden – 95 percent of malaria cases and 96 percent of malaria deaths. About 80 percent of malaria cases in this region were in children under the age of five.

Meanwhile, in 2020, 680,000 people died of HIV-related causes. There were 1.5 million new cases of HIV infection in 2020, while there were an estimated 37.7 million people living with HIV worldwide. The majority of those infected with the virus – 25.4 million – live in Africa.

The history of ribonucleic acids

mRNA technology has been in development since the 1960s, but it proved to be responsive when SARS-CoV-2 hit the world. Its success in combating COVID-19 has led to a renewed interest in developing technology for other diseases.

In short, mRNAs are messenger RNAs that induce an immune response from cells before they are degraded. They work by inserting a coding sequence of a disease-specific antigen – a substance that causes the body to make antibodies against it; Once this antigen is produced inside the body, the immune system can recognize it and prepare to fight the real virus, bacteria, or parasites.

Before the COVID-19 pandemic, exploration began in mRNA vaccines for a range of diseases, including Ebola, Zika, and rabies, as well as cancers and influenza.

But the field has developed rapidly in the past few years. In a 2018 review, scientists based in the United States said that mRNA vaccines represent a promising alternative to conventional vaccine approaches due to their high efficacy, rapid development potential, low-cost manufacturing potential, and safe administration.

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

Why is mRNA technology so exciting?

Interest in mRNA technology has increased since it entered the mainstream during the COVID-19 pandemic. The full text of a single 2020 review of mRNA technology from researchers in Shanghai and Beijing has been viewed nearly 35,000 times and has more than 40 citations, giving it a significant impact factor in the world of scientific literature.

mRNA vaccines look promising because of the speed with which they can be developed and produced, their flexibility and ability to adapt to variables. US pharmaceutical company Moderna’s mRNA vaccine against SARS-CoV-2 began clinical trials 63 days after the virus genome was published. By comparison, the Gardasil vaccine for human papillomavirus (HPV) — which uses recombinant DNA technology — took 15 years to get approved for use, in 2006.

Advances in the stability of mRNA vaccines have led to an exponential increase in interest in the technology. mRNA vaccines were tested in the early 1990s, but there were concerns about production scale and their fragile stability, according to a 2019 study.

With the advances in the synthetic production of mRNAs, the technology is becoming more and more attractive. Other forms of safe and effective vaccines carry an attenuated virus or part of the virus, and it takes time to increase the volume of pathogens needed for mass production of vaccines, and then weaken the virus.

With the Coalition for Epidemic Preparedness Innovations (CEPI) setting the world on a mission to produce vaccines within 100 days of a new germ being identified, research and development groups — including a team at Oxford University that produced a 100-day preprinted vaccine blueprint — say they’re on the cutting edge. the challenge.

The future of messenger RNA vaccine technology

In the early months of 2022, there was a flurry of activities surrounding the transfer and development of mRNA technology, with the World Health Organization announcing additional sites for mRNA vaccine technology transfer centers, and German biotechnology company BioNTech naming sites for new production facilities in Africa.

Amid these announcements, global health leaders and scientists have repeatedly pointed to the potential for mRNA to carry the Big Three, as well as non-communicable health burdens such as cancer.

Clinical trials have already begun, or are expected to begin this year, for a candidate mRNA vaccine for HIV, malaria and tuberculosis.

But scientists temper their optimism with caution, because reaching the clinical trial stage does not always guarantee that a candidate vaccine will be safe and effective. Global health advocates say funding for vaccine research and development, and an ongoing focus on technology transfer and knowledge enhancement in the Global South, must continue apace.

Prescriptions for COVID-19 mRNA vaccines are severely restricted by pharmaceutical companies, which refuse to share patents with developing countries. To combat “vaccine hoarding” and global health inequality, the World Health Organization, a consortium of research organizations and a drug patent group came together in 2021 to launch the structure of mRNA vaccines, establishing the first mRNA research and transfer center in South Africa, with “speakers” in Brazil and Argentina .

In February, the World Health Organization announced that six additional countries in sub-Saharan Africa and North Africa would receive technology to enable them to manufacture COVID-19 vaccines as part of the initiative.

The World Health Organization said the mRNA technology could also be used for insulin to treat diabetes, cancer drugs and possibly vaccines for the three biggest killers of infectious diseases. The World Health Organization has said that centers for transferring mRNA technology will eventually enhance access to vaccines for all, strengthen health security and promote self-reliance in the future.

Diversifying RNA vaccine manufacturing capacity in low- and middle-income countries should be a global health priority, said Kate Stegmann, advocacy coordinator in Africa for the MSF Access Campaign. She said: “More regions producing mRNA vaccines as an essential preparedness against infectious diseases could enhance the response not only to COVID-19 and future infectious diseases, but also to existing diseases such as malaria, tuberculosis and HIV.”

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