As the world raptly awaits the first vaccines for COVID-19, scientists are hard at work developing potential boosters for vaccines. One method at their fingertips: strengthening our immune response with an ingredient called an adjuvant.
You may have heard about adjuvants recently in the news. But what are they, exactly?
We sat down with an immunology expert – 3M Scientist Mark Tomai, Ph.D. – to get a better understanding of how adjuvants work and how they can help us in the COVID-19 pandemic and beyond.
Tomai: In simple terms, an adjuvant is anything you can use in a vaccine setting to boost the immune response and enhance the efficacy of the given vaccine.
Adjuvants come from a variety of sources and have been used for decades. They were first used with diphtheria and tetanus vaccines. One of the hallmark adjuvants is the substance called alum – an aluminum derivative that is used to boost the immune response.
Over the last several years we’ve learned that if you are using a heat-killed vaccine, which contains the whole organism, those organisms have built-in adjuvants that boost the immune response. If you are using protein-based vaccines or subunit vaccines, they often require an adjuvant to provide that boost.
Q: How does an adjuvant work to boost our immune response?
Tomai: We all have immune cells in our bodies. Some of these immune cells express what are called toll-like receptors (TLRs), which are proteins that play a key role in our innate immune system. There are 10 human TLRs that are either expressed on the outside of the cell or inside the cell. They recognize foreign substances that are expressed by a variety of pathogens and then pass on appropriate signals to the immune cells, initiating an immune response.
3M developed a small molecule that is a dual TLR 7 and 8 agonist (3M-052) that can act as an adjuvant to boost the immune response to a variety of antigens that can be used in vaccines. The adjuvant was formulated in an emulsion by the Infectious Disease Research Institute (IDRI). Because the molecule activates cells expressing either TLR7 or TLR8, which are generally expressed on different immune cells, it is designed to activate a broad range of immune cells which leads to a more robust immune response.
Tomai: Some of the vaccines that 3M-052 is being used with include HIV, malaria, influenza, and SARS-CoV-2 vaccines. Currently, 3M-052 is being evaluated in a number of studies for use in combination with a number of COVID-19 vaccine candidates delivered by injection.
Q: Are 3M’s small molecule TLR agonists being used for anything besides vaccines?
Tomai: 3M’s TLR agonists are being used or evaluated for use in a number of applications beyond use as a vaccine adjuvant. They have demonstrated potent anti-tumor activity* and are being evaluated for use in treating cancer. The field of immuno-oncology is changing the way cancer treatment is being approached and immunotherapies are playing a crucial role in this arena. These TLR agonists also are being used to treat viral infections due in part to their ability to induce interferon, a molecule that has potent antiviral activity.
Tomai: There’s so much happening right now in the field of immunology, not only to fight the pandemic, but in treatments for numerous diseases, including cancer. It is incredible to come to work each day knowing that what we’re working on really has the potential to make a huge impact on peoples’ lives.
Q: Are you seeing promising results with the use of 3M-052 in COVID-19 vaccines?
Tomai: Yes, we are. Our adjuvant is showing great promise in numerous COVID-19 vaccine studies. These are a few examples:
1. Intratumoral immunotherapy with TLR7/8 agonist MEDI9197 modulates the tumor microenvironment leading to enhanced activity when combined with other immunotherapies. Mullins SR, Vasilakos JP, Deschler K, Grigsby I, Gillis P, John J, Elder MJ, Swales J, Timosenko E, Cooper Z, Dovedi SJ, Leishman AJ, Luheshi N, Elvecrog J, Tilahun A, Goodwin R, Herbst R, Tomai MA, Wilkinson RW.J Immunother Cancer. 2019 Sep 11;7(1):244. doi: 10.1186/s40425-019-0724-8.PMID: 31511088
2. Safety and clinical activity of intratumoral MEDI9197 alone and in combination with durvalumab and/or palliative radiation therapy in patients with advanced solid tumors. Siu L, Brody J, Gupta S, Marabelle A, Jimeno A, Munster P, Grilley-Olson J, Rook AH, Hollebecque A, Wong RKS, Welsh JW, Wu Y, Morehouse C, Hamid O, Walcott F, Cooper ZA, Kumar R, Ferté C, Hong DS.J Immunother Cancer. 2020 Oct;8(2):e001095. doi: 10.1136/jitc-2020-001095.PMID: 33037117
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