Vaccine Tech – Best Supporting Actors

April 24, 2024 - Kristin DeBellis, PharmD

The World Health Organization (WHO) will celebrate the 50th year of its Essential/Expanded Programme on Immunization (EPI), a coordinated mission to provide universal access to life-saving vaccines during this year’s World Immunization Week.1 While vaccine history can be traced back over 500 years, these past 50 years have witnessed important advances. Eradication of smallpox around 1980 marked a key programmatic success that spurred public-private partnerships, and innovations geared toward improving safety, efficacy, and the supply-chain followed, including the groundbreaking production and distribution of messenger RNA (mRNA) vaccines.1,2


Rather than using whole pathogens, some vaccines now include only partial components (antigens), known as antigen subunit vaccines, designed to stimulate the immune system. However, these may need an added agent to induce an adequate and longer response – adjuvants.3 Adjuvants are now found in diverse immune-based therapies for allergies, cancer, and autoimmune diseases.3-5 Additionally, they can be credited with improving vaccine stability, reducing the required dose and frequency of administrations, providing response in patient population with immune challenges, and aiding development on a scalable level.4,5

The most common adjuvants are aluminum salts, still used today after nearly a century. They were initially devised as a purification and delivery system but were also found to improve immune response.5 Interest in finding adjuvants to help provide longer-lasting, disease-specific, and population-specific immune response (e.g., neonates, pregnant women, older adults, immune-suppressed individuals) led to the creation of the US National Institute of Allergy and Infectious Diseases (NIAID) within the National Institutes of Health. Launched to support adjuvant research and development programs in 2004, NIAID established its first strategic plan in 2010. Between 2009 and 2018, 5 new adjuvant compounds were employed in US Food and Drug Administration (FDA)-approved vaccines.4,6 NIAID established an online Vaccine Adjuvant Compendium in 2020 as a searchable repository for adjuvant developers and vaccine researchers to readily share their findings; more than 80 formulations are currently listed, with their corresponding immune profile, administration route(s), and investigational uses.4,7

Aside from the most prevalent, aluminum salts, 4 adjuvants are currently used in FDA-approved, commercially available vaccines, and others are in vaccines maintained in the Strategic National Stockpile.8,9 In 2015, the FDA approved the FLUAD® influenza vaccine for people ≥65 years of age containing MF-59®, a water-in-oil emulsion adjuvant made from squalene, an oil occurring naturally in plant cells. It has been found to provoke a improved response in infants, older adults, and other at-risk persons.5,6,9 A similar enhanced response in targeted populations was found with the adjuvant system AS01, liposomal formulations composed of a lipid plus a natural extract from a soapbark tree, called saponin, currently used in the Shingrix® shingles vaccine, and is being tested in investigational malaria and HIV vaccines.8-10 CpG systems, various synthetic forms of DNA are available in several motifs, with CpG 1018 used in the FDA-approved Heplisav-B® hepatitis B virus vaccine.8,9

Some vaccines, including the commonly used measles/mumps/rubella, and recently deployed mRNA vaccines for COVID-19 are considered self-adjuvanted, meaning they provoke a robust immune response without the need for an adjuvant.8,11 However, mRNA technology still presents large-scale production challenges and ultra-cold storage limit worldwide access.10 The Novavax Covid-19 vaccine candidate, an antigen subunit type, uses their proprietary Matrix-M™ adjuvant made of saponins, cholesterol, and phospholipids, received FDA Emergency Use Authorization in 2022.8,11 Data so far indicate this formulation provokes a good immune response across different strains of the SARS-CoV-2 virus, including in those patients who are immunosuppressed.11,12 Novavax COVID-19 can be refrigerated prior to use, thus helping to solve a key storage issue.10,13


Aside from the saponin-based adjuvants discussed, momentum is building behind plant products for a variety of reasons. Their mucosal absorption capabilities make them unique candidates for oral vaccinations, and they are considered environmentally nontoxic. Inulin has been found by the FDA to be safe, renewable, and biodegradable. A delta particulate form developed under the NIAID program and is currently being studied across a wide range of disease targets.14

Data so far indicate this formulation provokes a good immune response across different strains of the SARS-CoV-2 virus, including in those patients who are immunosuppressed.

As these products begin to reshape the landscape of available vaccines, it is clear that COVID-19 will not be the only disease for which multiple options will be available from which to choose. The day is coming when the need to understand the qualities adjuvants impart will be as important as knowing the mechanism of the active agent. Start now by reading any of the following resources:


The WHO’s EPI has come a long way in the last 50 years, but the award for Best Performance by a Supporting Actor goes to adjuvants for their shining performance in new vaccine technology over the past decade.





1. 50th anniversary of the Expanded Programme on Immunization (EPI) ( Accessed February 14, 2024.



2. College of Physicians of Philadelphia. History of vaccines. Vaccine timeline: before Jenner to after COVID-19. Accessed February 14, 2024.



3. NIH-NIAID. Vaccine types. Accessed February 22, 2024.



4. NIH-NIAID. Vaccine adjuvants. Accessed February 22, 2024.



5. Facciola A, Visalli G, Laguna A, et al. An overview of vaccine adjuvants: current evidence and future perspectives. Vaccines (Basel). 2022;10(5):819. doi:10.3390/vaccines10050819



6. NIH-NIAID. 2018 NIAID Strategic Plan for Research on Vaccine Adjuvants. NIAID. Accessed March 27, 2024.



7. NIH-NIAID. Vaccine Adjuvant Compendium (VAC). Accessed March 12, 2024.



8. Vaccine safety. Adjuvants and vaccines. Accessed February 22, 2024.



9. Common ingredients in FDA-approved vaccines. Accessed March 12, 2024.



10. Nanishi E, Angelidou A, Rotman C, et al. Precision vaccine adjuvants for older adults: a scoping review. Clin Infect Dis. 2022;75(suppl 1):S72-S80. doi:10.1093/cid/ciac302



11. Stertman L, Palm AE, Zarnegar B, et al. The Matrix-M™ adjuvant: a critical component of vaccines for the 21st century. Hum Vaccin Immunother. 2023;19(1):2189885. doi:10.1080/21645515.2023.2189885



12. Mueller-Enz M, Woopen C, Katoul Al Rahbani G, et al. NVX-CoV2373-induced T- and B-cellular immunity in immunosuppressed people with multiple sclerosis that failed to respond to mRNA and viral vector SARS-CoV-2 vaccines. Front Immunol. 2023;14:1081933. doi:10.3389/fimmu.2023.1081933



13. Novavax COVID-19 Vaccine, Adjuvanted. Package insert. Novavax Inc; 2023. Accessed March 27, 2024.



14. Kumar A, Sharma A, Tirpude NV, et al. Plant‑derived immuno‑adjuvants in vaccines formulation: a promising avenue for improving vaccines efficacy against SARS‑CoV‑2 virus. Pharmacol Rep. 2022;74(6):1238-1254. doi:10.1007/s43440-022-00418-4