Vaccine Adjuvants

Efforts to develop safe and effective vaccines increasingly involve the use of adjuvants—substances formulated as part of a vaccine to boost immune responses and enhance the vaccine’s effectiveness. NIAID plays a leading role in the discovery, development, and characterization of new vaccine adjuvants. 

Why is the Study of Vaccine Adjuvants a Priority for NIAID?

Researchers can use adjuvants to improve the efficacy of available vaccines, to help design new or improved vaccines for infectious diseases, or to help develop vaccines for treating allergies, autoimmune diseases, and cancer. 

Vaccine adjuvants augment and help guide immune responses to antigens, the vaccine components that elicit pathogen-specific immune responses. Certain populations, such as people with compromised immune systems, pregnant people, older adults and the very young, may particularly benefit from adjuvanted vaccines because their immune systems have unique characteristics and needs and may require an extra boost to provide protection. Adjuvants also can make it possible for a vaccine to achieve high efficacy using less antigen, which in some cases may be in short supply or costly, and this may expand the number of vaccine doses available. Additionally, adjuvanted vaccines can elicit more durable immune responses, reducing or eliminating the need for booster vaccinations and thereby simplifying immunization schedules.  

How is NIAID Addressing This Critical Topic?

The goal of NIAID’s vaccine adjuvant research programs is to develop a “toolbox” of adjuvants that can be matched with antigens to optimize vaccine efficacy. This goal is articulated in the 2018 Strategic Plan for Research on Vaccine Adjuvants. NIAID supports a broad portfolio of vaccine adjuvant research ranging from basic immunology studies to clinical testing of adjuvanted vaccine candidates. 

To foster collaboration between NIAID-supported vaccine adjuvant researchers and the broader scientific community, NIAID established the Vaccine Adjuvant Compendium (VAC) in 2020. This web-based tool displays adjuvant characteristics to help vaccine developers identify those adjuvants suitable for the disease they want to prevent.   

History of Vaccine Adjuvants

Aluminum salts have been safely used as vaccine adjuvants since the 1930s and are still widely used today. As technologic and scientific advances increased researchers’ understanding of human immunity, new insights led to the identification of novel adjuvants and many promising adjuvant candidates. Five new adjuvants have been approved for use in vaccines in the United States since 2009. Visit the Centers for Disease Control and Prevention's web page on questions and concerns about adjuvants and vaccines for a list and description of adjuvants used in approved U.S. vaccines.

NIAID Advances in Vaccine Adjuvant Research 

A novel adjuvant developed with NIAID funding contributed to the success of a highly efficacious COVID-19 vaccine called COVAXIN, which received Emergency Use Listing by the World Health Organization in 2021 and approval in 14 countries as of May 2022. The adjuvant, Alhydroxiquim-II, was discovered and tested in the laboratory by the biotech company ViroVax LLC of Lawrence, Kansas. The adjuvant comprises a small molecule attached in a unique way to Alhydrogel, a substance frequently called alum that is the most commonly used adjuvant in vaccines for people. Alhydroxiquim-II travels to lymph nodes, where the small molecule detaches from alum and activates two cellular receptors. These receptors, TLR7 and TLR8, play a vital role in the immune response to viruses. The NIAID Adjuvant Program has supported the research of the founder and chief executive officer of ViroVax since 2009. Learn more about Alhydroxiquim-II and the 2019 meeting that led the company Bharat Biotech to select this adjuvant for the COVID-19 vaccine that became known as COVAXIN.

COVID-19 vaccines based on just a fragment of the Spike protein from SARS-CoV-2 may be more affordable for low- and middle-income countries to produce at scale than the many COVID-19 vaccines based on the entire Spike protein. However, the key Spike fragment that binds to people’s cells—the receptor binding domain, or RBD—does not elicit a strong immune response on its own, especially in older individuals. To overcome this problem, researchers supported by the NIAID Adjuvant Discovery and Development Programs screened multiple vaccine adjuvants either alone or paired with aluminum hydroxide to find a formulation that would boost the immune response to the RBD protein the most. The investigators discovered that a vaccine combining the protein with two adjuvants, aluminum hydroxide and CpG (a short piece of DNA), worked best. Giving both young and aging mice this adjuvanted vaccine elicited neutralizing antibodies to SARS-CoV-2 at concentrations comparable to those induced by the Pfizer-BioNTech COVID-19 vaccine and protected aging mice from SARS-CoV-2 infection. The experimental vaccine also activated human immune cells donated by older adults. The findings were published in the journal Science Translational Medicine in 2021.  

Additional Resources

For more information about adjuvants and other vaccine ingredients, see FDA’s Q&A about Common Ingredients in U.S. Licensed Vaccines. For a general overview of adjuvants and a list of adjuvants included in vaccines licensed in the United States, see CDC’s Adjuvants Help Vaccines Work Better web page.

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