The entire scientific community is cheering for the early COVID-19 vaccine data from Pfizer and BioNTech. The 90% efficacy result shows that mRNA injection can indeed work.
This is important for brand new technologies that have not yet seen a single approved product. Coronavirus has been shown to prove that it can quickly transfer to a pandemic pathogen. But is it useful in other diseases? Two industry observers believe that the situation may be different.
SVB Leerink analyst BioNTech’s Daina Graybosch (Daina Graybosch) said in an interview that the early success of the COVID vaccine will “open”
Before the efficacy reading, the industry already knew that this injection, called BNT162b2, can trigger strong neutralizing antibodies, binding antibodies, CD4 and CD8 T cell responses. Graybosch said that although we still don’t know which one of them (even the immune component that scientists didn’t measure) drives the injection effect, at least we know that the vaccine is likely to be effective against this infection.
Flexible infectious disease platform that can
Graybosch is also hesitant to study other unknown mRNA candidates (such as Moderna’s mRNA-1273). Pfizer/BioNTech’s data undoubtedly has a positive impact on Moderna’s plan, but the two platforms are indeed different.
Graybosch pointed out that, for example, Moderna injection is not as good as Pfizer in enhancing CD8 T cell responses. This may be due to different assay methods used by researchers to measure CD8, or it may be due to real differences in platforms.
Graybosch said: “BioNTech CEO UğurŞahin has suggested optimizing its platform to get more antigen expression directly in the antigen presenting cells of the spleen, which will give you a truly powerful CD8 T cell response.”
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Wolfe Research analyst Akash Tewari also opposes the idea of integrating all mRNA technologies into one “platform” basket.
Tewari said: “One of the most important things for me is the difference between the three mRNA methods of Pfizer/BioNTech, CureVac and Moderna.” He pointed out the different “treatment windows” (ie optimal doses) of vaccines. And the CD8 T cell response of BNT162b2.
For mRNA vaccines, genetic information encoding protein antigens needs to be effectively transmitted to cells. Tewari said: “It is not easy to do in itself, and it is not necessarily a platform transaction.”
What these three people have in common is that “mRNA seems to be a very flexible platform in the context of COVID,” Tewari added. In the early research work, BioNTech had about 20 candidates. Before choosing BNT162b2, they were narrowed to four. He said: “Pre-clinical adjustment levels cannot be achieved by other technologies.”
In infectious diseases, we now know that mRNA can spin quickly to create truly complex antigens. Tewari said: “mRNA has demonstrated the ability to quickly get the product into the clinic, and then conduct different preclinical versions of the test in a relatively short period of time, so as to figure out what type of immune signature you want to promote.” “And it It also shows that mRNA can also induce many different immune characteristics.”
Graybosch proposed Shingrix, GlaxoSmithKline’s shingles vaccine, which requires an adjuvant to strike a good balance between T cell and antibody responses. She said: “Now that we have a second platform, it seems to be able to provide services for you.” “So I think we will see more efforts here, and it will accelerate.”
other illnesses?It’s too early
However, even in infectious diseases, Tewari warns that the efficacy of mRNA vaccines may be antigen-specific. Most of the COVID-19 vaccine candidates are focused on the spike protein of the new coronavirus, which plays a key role in infecting human cells. It happens to be an immunodominant antigen, which means that it can attract the immune system to attack, so it is an ideal target for vaccines.
However, there are other harmful areas of pathogens that are hidden, and less important components are transferred to the immune system. This may cause difficulties for mRNA and other more traditional vaccine technologies.
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Graybosch also believes that the positive reading range from Pfizer/BioNTech data to future mRNA vaccines depends on the target of each vaccine. This is the most promising “for environments that require very fast turnaround time to obtain new antigens”, such as pandemics and even flu seasons dominated by unexpected virus strains.
Treatment areas outside of infectious diseases may be more difficult to predict. Graybosch pointed out that cancer is the main focus of BioNTech and Moderna, but choosing the correct tumor-specific neoantigen has always been a challenge for all cancer vaccines. Tewari pointed out that due to the limited immune response that cancer vaccines can induce, some tumors cannot be resolved.
In fact, the flexibility of mRNA and its ability to induce multiple types of immune responses is impressive, “but to say that COVID data means that cancer vaccines will definitely work, which is scientifically irresponsible,” Tewari said .
Rare opportunity for acceleration
The government’s huge investment in the mRNA-based COVID program has greatly accelerated the company’s R&D process and helped make up for the expensive manufacturing scale. Graybosch said: “I think the biggest advantage of doing this is that you can give them cash to do the experiments they want.”
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Unlike infectious diseases, immuno-oncology takes a long time to signal, and investors don’t necessarily pay. Before publishing COVID, BioNTech focused on cancer. She said that now, Graybosch estimates that the company will have more infectious disease programs to provide “continuous cash inflows to support long-term, more challenging, and risky work in the field of immuno-oncology.” “.
More importantly, Graybosch believes that the rise of mRNA as a proven new vaccine platform may change the traditional positioning of the “big four” vaccine giants, such as Sanofi, GSK, Merck and Pfizer. She said: “Because of the work on COVID, some new players have emerged here. They will have manufacturing capabilities and have a lot of scale and experience.”
At present, the four giants have already cooperated on mRNA. Pfizer has established a cooperative relationship with BioNTech. GSK chose CureVac to study up to five mRNA-based vaccines and monoclonal antibodies. Merck and Moderna have been cooperating in oncology, although the New Jersey pharmacy recently dispatched an RSV candidate. Sanofi recently doubled its investment in Translate Bio.