Archaeosomes: Extreme Microbes Lead to New Vaccines for Cancer and Intracellular Pathogens

NRC researchers have discovered that the toughest microbes in the world make the best vaccines. Archaea, microbes that live in the most inhospitable environments on Earth, have special membranes to help them survive boiling heat, freezing cold, acid, alkaline and salty wastes.

Growing Bacteria for Vaccines

Fat molecules from these microbes' membrane formulated into a vaccine can provoke our most powerful immune response. Evidence indicates that these fats, or lipids, goad our immune systems into mopping up viruses such as HIV, bacteria that cause tuberculosis and even cancer cells.

This technology was recently licensed to Nicholas Piramal India Limited, one of India's largest healthcare companies. It could provide a booster shot to the vaccine market which is expected to grow from $4 billion to $20 billion over the next 10 years.

"We anticipate that this new adjuvant will lead to protective vaccines against difficult diseases such as TB which lacks an effective vaccine and kills millions every year," said inventor Dennis Sprott, Group Leader in Immunomodulation at NRC Institute for Biological Sciences (NRC-IBS).

Cells of Methanobrevibacter smithii (as viewed under a microscope), one of several archaeal species used for obtaining the polar lipids used to make archaeosomes.

Archaea provocateur

Archaea are called 'extremophiles' because they live in radically hostile environments such as volcanoes, deep sea vents, alkaline flats and glaciers. Their extra-tough and highly stable membranes help the microbes survive because the membranes' lipids are biochemically resistant to breakdown by oxidation, heat, cold, acid, alkaline or salt.

When you take the proteins out of the microbial membranes, the remaining lipids form a little bubble called a liposome. Inserting a chemical or protein inside the liposome prevents the chemical or protein payload from getting digested as it travels through the gastrointestinal tract on the way to the bloodstream. Sprott and fellow scientist Girish Patel, Group Leader of Infections and Immunity, suspected that liposomes made from archaeal membranes (or archaeosomes, as Sprott has coined the term) could have advantageous properties.

"We were already working on the structure of their unusual lipids," said Sprott, "so we decided to try them to make liposomes for drug delivery."

In addition to being tough, archaeosomes are very good adjuvants. Adjuvants are immune-stimulating compounds added to vaccines to boost the body's immune response. Another NRC collaborator, Dr. Lakshmi Krishnan, discovered that archaeosomes provoke several different types of immune reactions including the lethally effective 'cytotoxic T-lymphocyte response'. Neither of the two FDA-approved adjuvants used in current vaccines provokes this kind of immune response, which is the body's most effective mechanism to root out pathogens hiding inside our cells.

"You have to have a cytotoxic response to kill cells of other types. This is what you need in vaccines against cancer and viruses like HIV or bacteria like TB," said Sprott. "The reason we don't all die from cancer at a young age is thanks to our cytotoxic response; our T cells become hunters for malignant cells and kill them."

Tough enough to make it to market

The licensing deal to Nicholas Piramal India Limited was a high point in the long and fruitful collaboration among Sprott, Patel, Krishnan, and others NRC scientists.

"Lots of different types of expertise were used to bring this technology to the level where it is now," said Patel. He credits this achievement to the specialized lab facilities and wide-ranging expertise in biochemistry, bacterial culture, immunology, toxicology and business development at NRC-IBS.

"There were scientific and market challenges," said Patel. "In the beginning of the project, nobody knew whether we could make vesicles out of these lipids." It didn't help that the very best adjuvant came from the most anaerobic, or oxygen-sensitive, species of archaea around. Growing a large enough batch of these exotic microbes to harvest their membranes required specialized equipment and procedures.

"Another challenge was developing the intellectual property portfolio," said Patel. "I went to the US patent office six times to defend the technology."

The team brought additional expertise on board as the project evolved. After figuring out the immune response and running toxicology tests to ensure the vaccine was safe, the final challenge was to get a company involved.

"What really mattered to the company was that we had the scale-up procedure, we had the proof of principle in cancer and infectious disease, we showed that there were no safety issues and we had a strong intellectual property portfolio," said Patel.

Patel also recognizes the impact of NRC's innovation culture. "We're tuned into commercial interests and what we can do for companies. We're lending focus and expertise to help their objectives as a business. We have mitigated the company's risk."

75 L fermenter vessel in the Bacterial Culture Facility of NRC-IBS, one of several vessels used for cultivation of archaeal species.

Vaccines: not just for prevention anymore

Collaborative research between NRC-IBS and Nicholas Piramal to study the archaeosomes' impact on immunity is ongoing. According to Sprott, researchers are developing vaccines to treat conditions that chemical-based pharmaceuticals can't defeat.

"New diseases are emerging and antibiotic resistance is becoming a concern, so there is a new push for vaccines to get around the antibiotic problem."

In the future, a shot in the arm might be all we'll need to protect us against lurking pathogens or our own malfunctioning cells. Scott Ferguson, Business Relations Officer at NRC-IBS, has high hopes for archaeosomes as they make their way through clinical trials.

"The NRC archaeosome technology could revolutionize the vaccine industry with its novel capacity to both deliver the vaccine payload and to provide an increased response via its adjuvant ability."

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