Compounds called adjuvants are key to making vaccines created from inactive viruses strong enough to generate an immune response. Now, researchers think they may have found one of the most potent adjuvants yet: an immunomodulating small molecule called PVP-037.
“In principle, this compound can be added to any vaccine to enhance its action,” Ofer Levy, M.D., Ph.D., a Boston Children’s Hospital scientist and the lead author on a July 3 Science Advances article describing the discovery, said in an accompanying press release. “PVP-037 is one of the most active adjuvants we’ve discovered, and we think it induces a greater, more durable, and broader immune response to vaccines.”
The researchers identified PVP-037 by screening a 200,000-plus library of small molecules found in human immune cells. Of the 25 hits the analysis returned, PVP-037 was the most active.
The compound is what’s known as an imidazopyrimidine, a versatile molecule often used in drug development across a wide range of diseases. Cell studies on donor immune cells showed that PVP-037 activated immune pathways and cytokine production. In mice, an optimized form of the adjuvant boosted antibodies against flu and SARS-CoV-2, the virus that causes COVID-19, when given alongside disease-causing antigens.
Of course, efficacy alone isn’t enough—for an adjuvant to be useful, it needs to be easily integrated into the vaccine development timeline. Here, too, PVP-037 seems to be a good fit. The compound is stable and can be formulated in most drug delivery systems, like oil-in-water emulsions. It’s also easy to work with, according to the researchers.
The study is limited by the fact that the experiments were in mice and that the mechanisms by which the adjuvant works weren’t totally clear. Further, the researchers still need to study how it performs in the presence of actual pathogens, not just key proteins, they wrote in their paper. There are other details to work out as well.
“Immunization studies were undertaken at relatively short time points, such that future studies are needed to assess the impact of PVP-037 on durability of immune responses,” they wrote in the article. “Although we focused on [antibody] responses as important correlates of protection against influenza and SARS-CoV-2 … further studies should assess T cell responses … along with toxicity studies on stable formulations.”
Meanwhile, Boston Children’s and the researchers have already patented the adjuvant and plan to use funds from the National Institute of Allergy and Infectious Diseases to study whether the adjuvant works across age groups. They’ll be looking at its performance inside influenza, whooping cough and opioid vaccines to prevent fentanyl overdose deaths, according to the press release.
The work on imidazopyrimidines as immunomodulatory compounds has been patented, too, and will eventually be studied for applications in allergy and cancer treatments.