The mRNA platform will continue to grab headlines for a while as it made history thanks to Moderna and Pfizer producing the world’s first and fastest Covid-19 vaccines using the mRNA platform. Of course, producing a vaccine in just 11 months is no small feat when compared to the usual 10-15 years required for vaccine manufacturing.

Still, the Coalition for Epidemic Preparedness Innovation (CEPI) is encouraging biopharmaceutical companies to respond even faster with its moonshot goal of making vaccines available within 100 days to avoid the devastating impacts of future pandemics.

In this regard, Dr. Tore Godal, founding CEO of GAVI, spoke about some vaccine innovations which CEPI is supporting in the Indo-Pacific Region at a vaccine cooperation forum held in Korea in December.

Current Covid-19 vaccine status

According to the latest statistics from the World Health Organization (WHO), there are 11 vaccines granted emergency use worldwide which include RNA, protein subunits, non-replicating viral vectors, and inactivated vaccine types.

In Korea, a similar variety is made available with eight approved which includes only one domestically made protein subunit type vaccine from SK Bioscience called SKYCovione. However, other Korean biopharmaceutical companies have quickly joined in the race with a further nine vaccines currently undergoing clinical trials. Among them, the most advanced ones include protein subunit vaccines from Eu Biologics and SK Bioscience and a DNA vaccine from Inovio.

Molecular clamp vaccines on the horizon

Molecular clamp vaccines are subunit vaccines and are so-called because of their ability to clamp the antigen of the virus in the state before fusing with its target cell, also known as the pre-fusion state. Many subunit vaccines usually target the fusion proteins of the virus but it usually changes shape upon binding to the cell. Accordingly, the molecular clamp technology works by locking the fusion protein of the virus into its pre-fusion state to allow for an optimal immune response.

Just like the mRNA platform, it requires the viral protein’s genomic sequence, which is then coupled with an optimized clamp sequence to produce a synthetic antigen, purified and rapidly manufactured into a vaccine.

The University of Queensland, CEPI, and CSL partnered to advance the development of a Covid-19 vaccine candidate with another promising platform called the molecular clamp vaccine. However, it suffered a temporary setback returning weak false-positive HIV screening results in some tests as the molecular clamp was derived from fragments of an HIV spike protein, Gp41 which was undesirable for future HIV screening tests.

Nevertheless, CEPI believed in this sub-unit vaccine platform and pledged $5.7 million (7.4 billion won) in November 2022 to develop the re-engineered second-generation molecular clamp vaccine, the Clamp2 platform, which overcomes the previous diagnostic issue. The team has already demonstrated its equivalence to the original platform in preclinical trials and is scheduled to begin clinical trials this year.

Although the platform will be validated against a currently licensed Covid-19 vaccine, the researchers aim to use this platform to progress other therapeutic and vaccine candidates in need like the endemic HTLV-1 virus in Australia, stating that the Covid-19 vaccine market is already saturated.

Benefits of the molecular clamp vaccine platform

This platform was first studied using 10 different viruses including Ebola, Lassa virus, MERS, varying influenza types, and Nipah viruses. As this platform still has to undergo clinical trials, a direct comparison cannot yet be made against the mRNA platform which has been well-studied. However, based on published studies, this platform can be leveraged for its speed against emerging infectious diseases as it does not require previous knowledge of the virus’ protein structure and can be synthesized remotely using genetic sequence information alone.

Additionally, as the clamp can target the prefusion protein of the virus, it is often more protective than other sub-unit vaccines which usually target the post-fusion form. Regarding safety, cytotoxic components can be removed to only contain viral fragments without replicative components for improved safety over other vaccine types.

Furthermore, subunit vaccines are scalable, and antigens can be designed and formulated for enhanced thermostability, reducing deployment costs to increase vaccine affordability and access.

Commenting on whether this new platform could be beneficial for Korea’s vaccine manufacturing hubs, IVI’s Europe Regional Office Head and Deputy Director General Anh Wartel explained, “IVI is not currently involved in any project using the molecular clamp technology approach but is supporting vaccine manufacturers using various platforms like the inactivated, DNA, mRNA, protein-based adjuvanted, and adenoviral vectors to accelerate vaccine R&D against SARS-CoV-2 since February 2020 across preclinical, clinical as well as pre-and post-authorization studies,”

In this regard, we have been testing Covid-19 vaccines from companies that have committed ~1 billion doses of Covid-19 vaccines to COVAX facility, for global supply including LMICs, she said.

Wartel went on to say that IVI is no stranger to collaborating with multiple manufacturing partners to advance innovative vaccine technologies, and can help with tech transfers to Korean partners in this field.

What’s new in mRNA?

With all this buzz around the molecular clamp vaccine platform, both Moderna and BioNTech/Pfizer, giants in the mRNA business, have not announced any R&D plans for this newer platform and are focusing their efforts on further developing the mRNA platform. Although significant achievements have already been made with the mRNA platform regarding the Covid-19 vaccines, other areas like cancer, influenza, and RSV vaccines are still undergoing clinical trials.

Among these, cancer mRNA vaccines seem to be the most advanced with both giants again racing to commercialize a cancer vaccine. In this regard, Moderna’s cancer vaccine together with Merck’s Keytruda showed a reduction in the risk of death or recurrence by 44 percent in stage III/IV melanoma patients compared with Keytruda alone. Moderna is also ramping up its mRNA facilities with its acquisition of Japanese OriCiro, which produces cell-free synthesis and amplification of plasmid DNA, a key building block in mRNA manufacturing. More data will likely be revealed on Sunday (6:30 AM KST) as Moderna’s CEO Stephane Bancel is scheduled to present on the development of its personalized cancer treatment and vaccines using its mRNA platform at the world’s largest tech show, CES 2023.

Meanwhile, BioNTech plans to conduct an initial clinical test of BNT113, a vaccine candidate for head and neck cancer at its Taiwanese hub. Both Pfizer and BioNTech also announced in December that they received U.S FDA Fast Track designation for the single dose mRNA vaccine against both Covid-19 and Influenza to simplify immunization practices against two of the most prevalent respiratory viruses.

As the mRNA platform remains one of the most widely studied vaccine platforms today, BioNTech also launched its BioNTainers, a modular mini factory with the ability to manufacture 50 million doses a year. This initiative aims to enable scalable mRNA vaccine production and support for accessing novel medicines in Africa. Accordingly, the first BioNTainer is expected to arrive in Rwanda in the first quarter of 2023 and subsequently in Senegal and South Africa.