The power of mRNA: The technology's potential to tackle global health threats

By Rachel Arthur contact

- Last updated on GMT

Pic:gettyricharddrury
Pic:gettyricharddrury

Related tags: mRNA

After the success of mRNA with COVID-19 vaccines, a new partnership between Moderna and IAVI will seek to use the tech to target HIV/AIDS, tuberculosis, and antimicrobial-resistant enteric infections.

Announced this morning, the partnership will ‘combine the power of Moderna's mRNA platform and IAVI's expertise in discovery and product development to advance vaccines and antibodies.’

Heading up the program is a partnership for HIV antigen development: which entered a Phase 1 clinical trial in January and represents the first in-human mRNA HIV trial.

The partnership will also focus on making such vaccines and treatments globally accessible: especially in low income countries where the targeted diseases have high incidence and prevalence.

Large-scale push for mRNA

HIV/AIDS, tuberculosis (TB), antimicrobial-resistant enteric infections, and COVID-19 are estimated to have caused at least 95 million new infections and more than 4 million deaths in 2020 alone.

IAVI is an international organisation which focuses on translating scientific discovery into accessible solutions. Following the success of mRNA technology in COVID-19 vaccines, it’s now turning its focus to the tech in a large-scale push towards other diseases.

“Moderna’s proven, innovative platform has the potential to be a key that unlocks rapid production of vaccine and antibody candidates that could significantly accelerate our ability to solve the most difficult public health problems,”​ Mark Feinberg, M.D., Ph.D., president and CEO of IAVI.

“IAVI’s partnership with Moderna is a unique example of two organizations with complementary expertise and shared goals combining the best of our science to address urgent global public health needs.”

Targeting HIV

The program furthest along in development is a Phase I clinical trial, IAVI G002​, of HIV vaccine antigens being delivered by mRNA.

The trial was initiated in January 2022 and is testing vaccine antigens that were originally developed as proteins by a team led by William Schief, Ph.D., professor at Scripps Research and executive director of vaccine design at IAVI's Neutralizing Antibody Center (NAC).

Results from the IAVI G001 clinical trial showed that an adjuvanted protein-based version of the immunogen eOD-GT8 60mer induced the desired B cell response in 97% of recipients. IAVI G002 takes this concept further: it will determine whether mRNA-encoded eOD-GT8 60mer followed by an additional mRNA-encoded immunogen induces further maturation of B cells.

This trial, funded by the Bill & Melinda Gates Foundation, represents the first time mRNA for HIV vaccines is evaluated in humans. Another Phase I trial is expected to begin this year in South Africa and Rwanda.

This trial, IAVI G003, is sponsored by IAVI and supported by the US President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID). Additional support is provided by the Bill & Melinda Gates Foundation through grants to Moderna and to the Collaboration for AIDS Vaccine Discovery Vaccine Immunology Statistical Center.

The trial will assess whether receipt of the priming vaccine antigen being evaluated in IAVI G002 in U.S. populations induces similar responses in African populations. Eventually, through these and future trials, the partners hope to demonstrate proof-of-principle for the elicitation of HIV broadly neutralizing antibodies in humans via the vaccine approach pioneered by Dr. Schief's lab.

Preclinical programs

Meanwhile, the other joint IAVI-Moderna programs - for TB vaccine candidates and antibodies for SARS-CoV-2, HIV, and antimicrobial-resistant enteric pathogens - are in preclinical stages.

Tuberculosis is a notoriously difficult area for vaccine development. Responding to these challenges, the tuberculosis collaboration will focus on researching a set of promising antigens that could bring  'much-needed diversity' to the global preclinical TB vaccine pipeline.

For the antibody programs, scientists at the NAC are collaborating with Moderna researchers with the aim to improve the antibody-mRNA platform and establish proof-of-concept for testing in humans.

mRNA potential

Outside the IAVI-Moderna program, a number of programs are seeking to embrace mRNA for various targets. 

Moderna also has another HIV program: taking its HIV trimer mRNA vaccine into clinical trials last month.​ Three new development programs were announced earlier this year for vaccine candidates​ against herpes simplex virus, varicella-zoster virus and a new checkpoint cancer vaccine. The three new projects will build on learnings from the company's COVID-19 vaccine; and join other candidates in Moderna's pipeline which include a flu vaccine, RSV vaccine, and Zika vaccine.

BioNTech has set its sights on malaria​: believing that the tech could prove successful in another area which, like tuberculosis, is a large health threat that has nevertheless proved tricky for vaccine development in the past (while more than 100 vaccines have entered clinical trials, none had reached the WHO's efficacy goal until a Phase 2 study for a University of Oxford candidate​ last year)

Pfizer, meanwhile, pledges to continue to capitalize on its strengths in both mRNA R&D and manufacturing. Speaking in February, CEO Albert Bourla said the company's strategy has two pillars: focusing firstly on expanding the vaccine portfolio and secondly by exploring where the tech can go next.

It pledges to grow its portfolio of prophylactic mRNA vaccines: including vaccines for shingles, flu, and other infectious diseases (particularly viral). It already has a pre-COVID agreement with BioNTech on a flu vaccine, signed in 2018. The two companies also see an opportunity to create a shingles vaccine​​​ with higher efficacy and better tolerability than those on the market: with clinical trials expected to start in the second half of this year. 

External agreements with BioNTech, Beam Therapeutics, Acuitas Therapeutics and Codex DNA also seek to push the boundaries in mRNA.

 

Related topics: Bio Developments