Boosting Efficacy of Vaccine through Metal-Organic Nanoparticles

Boosting Vaccines With Metal-Organic Nanoparticles

Vaccines work by safely exposing the body to pathogens, “teaching” the immune system how to react the day it meets the actual disease-causing virus or bacteria. The issue is that for the immune system to do so, it needs to be exposed to a minimum quantity of pathogens or fragments, which can sometimes be difficult.

For this reason, traditional vaccines use adjuvants like aluminum to boost the immune system’s reaction. However, these can cause unwanted side effects as they stimulate ALL immune reactions, not just the ones intended by the vaccine.

A research team from MIT might have found a solution to increase vaccine effectiveness by using a novel type of adjuvant leveraging nanotechnology. They used a nanoparticle called a metal organic framework (MOF) which acts as an adjuvant boosting a specific immune reaction instead of a generalized reaction like with classical adjuvants.

The research involved Robert Langer, an MIT Institute professor, and Dan Barouch, a professor at Harvard Medical School.

How Metal-Organic Nanoparticles Work

The published research paper explains that they used a MOF called ZIF-8, a zinc ion attached to four molecules of imidazole, an organic compound. This is the first time the mechanisms of how ZIF-8 works have been elucidated.

The researchers embedded  SARS-CoV-2 spike protein inside the structure of 100-200 nm ZIF-8 particles, with that size allowing it to be swallowed by macrophages or to enter lymph nodes. The MOF particles get broken down, delivering the viral protein straight to the immune system.

So, it essentially works by directing the viral particles to the immune system for detection instead of overstimulating the whole immune system to make it detect the viral particles in the bloodstream. Targeting viral particles created a very specific dose-dependent response to the COVID protein and a larger reaction than the protein without the MOF.

What makes it especially useful is that it mimics how the body builds immunity against the virus, with the digested virus being broken down in pieces and memorized for creating long-term immunity. So, from the immune system’s point of view, there is little difference between a ZIF-8 particle and a real viral particle.

What’s Next For Metal-Organic Nanoparticles and MOF Vaccines?

The discovery of how to use MOF without an adjuvant opened the way to an entirely new generation of vaccines that might be safer and more efficient.

Another advantage is that such vaccines using subunits of proteins are cheaper and easier to manufacture than RNA vaccines. So this could keep traditional vaccine designs competitive even against the new waves of mRNA vaccines in development.

The next step will be to do further tests to ensure the safety of ZIF-8 now that it has been proven that it can boost vaccine effects. Procedures for mass manufacturing at cost will also need to be developed.

Another possibility is that ZIF-8 is not the end point of MOF-based vaccines. Similar nanoparticles could display an even stronger immune effect, a better safety profile, or be easier & cheaper to mass manufacture.

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Vaccine Companies’ Stocks

1. Merck

While it was beaten in total revenues in the last few years by COVID-19 vaccine companies, Merck still held the #1 spot of non-COVID-19 vaccine sellers. Among its best sellers is the anti-HPV (Human Papillomavirus) vaccine Gardasil, bringing $8.8B in 2023, and explosive revenue growth in the last 3 years.

The company is also looking to launch a new pneumococcal vaccine with a PDUFA date set for its V116 vaccine in June 2024 and 5 other vaccines in the R&D pipeline.

Improving the efficiency of vaccines and reducing the need for adjuvants that can cause side effects will be of great interest to companies like Merck, which had to regularly deal with controversy over its vaccines, which may cause some rare diseases, including Gardasil.

So, while mRNA vaccines have been all the rage due to the pandemic, more traditional protein-based designs are far from over and can be massively profitable.

2. GSK

GSK is another heavyweight in vaccine production, notably with an advanced 5-in-1 meningococcal vaccine (for meningitis) that brought 1.1B in revenues in 2022, even if it is still yet to be approved for the US market.

The company is also working on expanding its vaccine offer. Its RSV vaccine targeting 50-59-year-old adults has been approved in January 2024, and is the first to be available for this population. More vaccines are in development, including for:

• Shingles.
• Influenza.
• Meningococcal diseases.
• Pneumococcal diseases.
• Hepatitis B
• Herpex simplex virus

GSK expects the vaccine category to keep growing at a “High-single-digit % CAGR”.

GSK’s focus on infectious diseases, through vaccines and new antibiotics, answers a pressing need in the context of rising antibiotic resistance and new epidemics. It is also the provider of adjuvants or manufacturing services to other companies’ vaccines, which puts it in a prime position to benefit from improvements in classical vaccines and manufacture them at scale.

3. Sanofi

Sanofi is another large leader in the vaccine market, with a strong presence in the yearly flu vaccine. It is also a leader in overall immunology, notably thanks to Duxipent, an anti-allergic therapy.

Sanofi’s R&D efforts rely on both traditional vaccine technologies and mRNA vaccines. By 2025, it expects to present at least 5 “best-in-class” new vaccine candidates in phase 3 of clinical trials.

As a result, the company expects its vaccine sales to grow to as much as $10B+ by 2030, mostly from a continuous lead in influenza, and growth in RSV, Pneumococcal, and new mRNA markets.

It is also working on innovative immunology technology platforms, like antibody-drug conjugate, SYNTHORIN, and leveraging the body’s Natural Killer (NK) cells, as well as combining these with AI and genomic research.

Sanofi is expanding in areas where vaccines tend to underperform, like infants with an immature immune system. And it is also looking to expand vaccines’ potential, notably by targeting acne.

Improvement in efficiency, like using MOF to create a strong immune response, could be a new path for the company to deliver even better medical performance, especially for diseases or situations where vaccines have historically failed to perform adequately.