Getting a boost: How adjuvants can improve vaccines for COVID-19

Q: What are adjuvants?

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.

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.

Q: What types of vaccines are being used in combination with 3M’s adjuvants?

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.

Tomai: Yes, we are. Our adjuvant is showing great promise in numerous COVID-19 vaccine studies. These are a few examples:

• Nature recently published an article showing the effectiveness of SARS-CoV2 immunization using the 3M-052 adjuvant along with a protein-based nanoparticle vaccine. The study showed induction of neutralizing antibodies to the immunizing strain as well as to the U.K., South African and Brazilian variants. This data suggests that this combination could potentially be used as a universal coronavirus vaccine – a vaccine to protect against a wide variety or coronaviruses, which is extremely exciting.
• A group of researchers at the University of North Carolina at Chapel Hill, Weill Cornell Medicine and NewYork-Presbyterian also reported promising pre-clinical results in vaccines for young children – showing safety and strong immunity in their study of vaccine candidates which used the 3M adjuvant.
• Researchers at Emory University have developed a protein platform vaccine candidate with the 3M adjuvant to induce a long-lasting antibody response to COVID-19.
• Researchers at Emory University,  Infectious Disease Research Institute (IDRI), 3M and Texas Children’s Hospital’s Center for Vaccine Development at Baylor College of Medicine were the first to show combining yeast-expression technology and a the novel adjuvant formulation to produce a COVID-19 vaccine candidate is effective against COVID-19. It shows potential to be easy to produce at large scale and cost-effective, important aspects for vaccinating people worldwide.

References:

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