Bacteria Striking Back
Bacterial infections are much less deadly than they used to be before the introduction of antibiotics.
“Before we had antibiotics, infections like scarlet fever could even lead to heart problems. Surgery often led to deadly infections in the blood like bacteremia or septicemia.
A World Without Antibiotics
Because antibiotics silently save so many lives every day, we have started to take them for granted. But this is far from a safe assumption. Bacteria evolve very quickly, and not dying from antibiotics is a strong evolutionary pressure. So, it is common for a new antibiotic to lose its efficiency after 10-15 years.
The only thing that kept antibiotics ahead of bacteria resistance was the effort of researchers to keep finding new molecules decade after decade. This is a silent war between researchers and pathogens.
Recently, pathogens started to win. Antibiotic resistance is a growing problem, especially concerning diseases contracted in hospitals. Antibiotic resistance kills more than 1.27 million people yearly worldwide. Very few new antibiotic classes have been discovered since 2000.
Source: Aphage
Due to this growing antibiotic resistance, some infections like Clostridium difficile have become more prevalent, especially in hospitals and among weakened patients, children, and the elderly.
- Difficile is an especially tricky infection because it attacks the digestive system. The main treatment is a lengthy course of antibiotics.
- However, because antibiotics also target beneficial bacteria in the gut microbiome, C. difficile often takes advantage of their absence, releasing toxins in the colon that allow C. difficile to prosper.
So the announcement of the development of a first vaccine against C. difficile is an important news. It was made by researchers at the Penn Medicine and Children’s Hospital of Philadelphia and published in the prestigious scientific publication Science, under the title “A multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection”.
C. difficile Infections
C. difficile is a bacteria causing infection of the colon, which can cause symptoms like diarrhea and fever and, in severe cases, up to bowel perforation, kidney failure, or death.
C. difficile infections (CDI) are affecting around 500,000 patients yearly in the USA and causing 30,000 deaths.
Another effect of CDI is that they tend to be re-occurring in 35% of the cases. Among these first re-occurring cases, 60% will re-occur further, potentially turning into a chronic issue.
As CDI affects mostly vulnerable populations, the very young or old people, or seriously sick, this can also reduce their recovery from other health issues. C. difficile spores are also very resistant, making their complete elimination in the environment difficult, especially in hospitals and healthcare centers.
C. difficile mRNA Vaccine
Because C. difficile targets mostly vulnerable patients, preventing the infections from occurring in the first place would be ideal.
However, an issue researchers have met in creating a vaccine against C. difficile is that the bacteria can hide in biofilms or very tough spores, making it appear in different forms to the immune system.
To tackle this issue, the researchers used the mRNA-LNP (Lipid NanoParticle) vaccine platform, the same platform that gave us the mRNA COVID-19 vaccines.
Contrary to traditional vaccines, mRNA vaccines can train the immune system to target the bacteria in several different ways.
“Where most vaccines are spurring one’s immune system to create specific antibodies, mRNA vaccines were a perfect candidate for a C. difficile vaccine because they can be easily packaged up to elicit the immune system to do more than one thing to protect against a bacteria, virus, or fungus,”
Drew Weissman, 2023 Nobel Laureate MD, PhD, and co-author of the study.
The C. difficile mRNA vaccine was designed to target an enzyme found in diverse strains of this bacterium that processes several surface factors required for gut colonization and virulence.
So not only should this help target the bacteria in general, but it should, at least in theory, affect especially the most virulent strains.
When tested in animal models, the experimental vaccine created a strong immune response against all forms of C. difficile, including vegetative cells and spores. The immune response was mediated through long-lived T cells, anti-toxin immunoglobulin G, and mucosal antibody responses.
Source: Science
This allowed for 100% survival of the mice, as well as no measurable impact on the rest of the gut microbiome, increasingly understood as a key factor in maintaining overall health.
Effect On Antibiotic Resistance
Growing antibiotic resistance threatens to cause a massive death toll in the upcoming years. By 2050 the deaths from antibiotic resistance could amount to 10 million per year, almost 10x more than the already heavy death toll of today.
“Antimicrobial resistance (AMR) has caused 1.27 million deaths directly in 2019, with 1 in 5 of the victims a child under 5 years old. And 4.95 million people who died in 2019 suffered from drug-resistant infections, such as lower respiratory, bloodstream, and intra-abdominal infections.”
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Some solutions might be deployed soon, like antibacterial polymers, or “living antibiotics” (bacteriophages).
But another ideal situation would be to avoid creating and propagating antibiotic resistance in the first place. This way, new molecule classes or therapeutic methods could last longer before the bacteria develop a way to escape them.
The more vaccines exist, especially for bacteria requiring heavy use of antibiotics like C. difficile, the less resistance will develop.
So not only could this vaccine reduce the growing issue of C. difficile antibiotic resistance and associated deaths, but it could also reduce the emergence and prevalence of antibiotic resistance for other diseases as well.
Expanding mRNA Applications
As we discussed recently in “Fighting Cancer with BioTech – Why mRNA Vaccines Are Such a Leap Forward,” mRNA technology is quickly expanding into new applications.
One such application is treating cancer, where the immune system is trained by the mRNA injections to find and kill cancer cells the way they do against Covid-19 with the pandemic vaccines.
Other mRNA therapy candidates are looking at treating other persistent diseases resistant to treatment, like Lyme disease, malaria, or the herpes simplex virus.
Ultimately, mRNA could even be used to treat allergies and auto-immune diseases, heal damaged organs, or be used for safer gene therapies.
Investing In mRNA Vaccines
mRNA has become, in large part due to the pandemic, a darling of investors in 2020-2022. The necessary cooling down of mRNA vaccine sales post-pandemic has caused the prices of many mRNA-related stocks to decline as a result.
This does not change the fact that technology is remarkably powerful in preventing diseases, from infectious diseases to cancer and maybe rare diseases, auto-immune syndromes, etc. And expertise in mRNA vaccines gives a serious head start to some companies in bringing this tech to new fields of medicine.
You can invest in mRNA companies through many brokers, and you can find here, on securities.io, our recommendations for the best brokers in the USA, Canada, Australia, the UK, as well as many other countries.
If you are not interested in solely mRNA companies, you can also look into biotech ETFs like WisdomTree BioRevolution UCITS ETF (WBIO), VanEck Biotech ETF (BBH), or First Trust NYSE Arca Biotechnology Index Fund (FBT), which will provide more diversified exposure to capitalize on the growing biotech economy.
Companies Offering mRNA Solutions
One of the leading companies in mRNA cancer therapies is BioNTech, which is building from its success in developing the Covid-19 mRNA vaccine commercialized by Pfizer.
Cancer
BioNTech currently has 11 different candidates in cancer treatments, covering cancer in the ovaries, prostate, intestines, skin, head, neck, and multiple solid tumors.
Most clinical trials on oncology treatment are in phase 1/2, with three candidates already in phase III.
Source: BioNTech
In total, the company has 21 clinical programs in oncology. This includes not only mRNA, but also small molecules, Immuno-Oncology agent (IO), and Antibody-drug-conjugates (ADCs).
The first oncology product is expected to be potentially launched in 2026.
Source: BioNTech
Infectious Diseases
BioNTech also stayed the leader in COVID-19 vaccines, with >50% market share, and upcoming combination respiratory vaccines (Covid + Flu/Influenza) in late 2025 or 2026 if approved.
Regarding infectious diseases, BioNtech is pursuing vaccines for shingles, Herpex, tuberculosis, malaria and Mpox. Among those, the diseases affecting the most people are Herpex viruses (3.7 billion people infected), malaria (249 million), and tuberculosis (10.6 million).
Source: BioNTech
AI
BioNTech is also very active in the AI-Biotech field, with the creation in 2020 and full acquisition in 2023 of the company InstaDeep AI.
Source: BioNTech
InstaDeep is the “first AI Immunotherapy Platform”, using LLM technology on DNA and protein sequences, AI vision for histology (tissues under a microscope) analysis, and AI agent for lab automation and quality control.
The goal is to deploy AI across the entire R&D pipeline.
It uses a supercomputing cluster with 224 Nvidia H100 GPUs and 86,000 CPU cores, with 0.5 ExaFLOPS, making it into the top 100 worldwide. InstaDeep’s genomics AI models are among the most downloaded, illustrating how they are “state-of-the-art” in this field.
Financials
The money from the pandemic gave the company a very strong position, with €16,9B in total available cash by mid-2024. In 2023, Covid-19 vaccines still generated €3.8B in revenues, for a gross profit of €3.2B.
This is likely to slow down in 2024, but overall, the company has very strong finances for what is still ultimately an early-stage biotech startup with only one product commercialized.
