Small Molecules Give Vaccines A Big Boost

Small molecule libraries represent a promising source of new vaccine-boosting ingredients, scientists find.

AsianScientist (Nov. 11, 2020) – As the world eagerly awaits the arrival of a COVID-19 vaccine, scientists in Japan are turning to small molecule libraries to discover new ingredients that make vaccines more effective. These ingredients, known as adjuvants, help elicit a stronger immune response when added to a vaccine. The team’s findings were published in the journal Angewandte Chemie.

Vaccines are typically divided into two main types. Live attenuated vaccines are produced by weakening a disease-causing bacterium or virus in the laboratory. When administered, the modified microorganism in the vaccine replicates in the body and generates long-lasting immunity.

In contrast, inactivated vaccines contain killed versions of the microbes, or components like proteins and sugars. Because these vaccines do not contain live bacteria or viruses, they cannot replicate and stimulate a strong immune response. Hence, adjuvants are often added to inactivated vaccines to accelerate, prolong or enhance their effect. While adjuvants have been used for nearly a century, how they actually work remains a mystery to scientists.

“Adjuvants generate a robust and long-lasting immune response, but the ones currently in use, like aluminum salts and oil-in-water emulsions, were developed in the 1920s,” explained study leader Dr. Motonari Uesugi of Kyoto University. “We don’t precisely understand how they work, which is why they are often called immunologists’ dirty little secret.”

Given the historically unclear understanding over adjuvants, it should come as no surprise that many existing adjuvant compounds were discovered through mere trial-and-error.

Seeking a more rigorous method to identify adjuvants, Uesugi and his team screened a library of 8,000 small molecules for their ability to self-assemble. Molecular self-assembly, where molecules self-organize without guidance from an outside source, is a naturally-occurring process in cells. This led the researchers to hypothesize that self-assembling molecules may resemble the structures of disease-causing microbes and stimulate an immune response.

From the library, the team identified 116 self-assembling candidates and then screened them for their ability to increase the expression of pro-inflammatory molecules. Eventually, Uesugi and his colleagues singled out cholicamide, which assembles to form a virus-like structure that enters the cell. Once inside, cholicamide generates an immune response through the same mechanism that detects single‐stranded viral RNA. When used as an adjuvant for the influenza vaccine and given to mice, cholicamide proved to be as potent as aluminum salts.

Further studies are needed to determine how cholicamide mimics the single RNA strands of viruses to stimulate the immune system. Still, their study shows that screening small molecule libraries represent a promising strategy for identifying vaccine adjuvants.

“Our study, to the best of our knowledge, is the first report of using a small molecule library for vaccine adjuvant discovery,” said Uesugi. “We hope the new approach paves the way for discovering and designing self-assembling small molecule adjuvants against pathogens, including emerging viruses.”

The article can be found at: Jin et al. (2020) Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants.


Source: Kyoto University; Photo: Mindy Takamiya/Kyoto University iCeMS.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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