An adjuvant is a substance that is formulated as part of a vaccine to enhance its ability to induce protection against infection. The word “adjuvant” comes from the Latin adjuvare and means “to help.” Adjuvants help activate the immune system, allowing the antigens—pathogen components that elicit an immune response—in vaccines to induce long-term protective immunity.
An effective vaccine stimulates both arms of the immune system: innate immunity and adaptive immunity. Innate immunity occurs within hours, as immune cells recognize a pathogen. Subsequently, the adaptive immune response develops over several days and involves coordination and expansion of adaptive immune cells called T and B cells. This leads to immune memory, when cells highly specific to the pathogen are retained for later use in case of re-infection. Adjuvants are important for activating the innate immune response, resulting in improved adaptive immunity with enhanced activation of T and B cells.
The first human vaccines were based on weakened or killed pathogens that cannot cause disease. These vaccines contain naturally occurring adjuvants and antigens from the incapacitated pathogen and can elicit strong protective immune responses. Many of these types of vaccines are still widely used. For example, the seasonal flu shot contains killed influenza virus and the nasal spray flu vaccine includes weakened virus, which is unable to cause flu illness.
Most vaccines developed today include only the antigens that best stimulate the immune system, such as proteins, rather than the entire virus or microbe. For example, the egg-free flu vaccine contains an influenza virus protein that is produced in cell culture. Although this design makes vaccines safer and easier to produce, it often requires the incorporation of adjuvants to elicit a strong protective immune response, because the antigens alone are not sufficient to induce adequate immunity and long-term protection.
The egg-free flu vaccine contains hemagglutinin (HA), the surface protein that binds influenza virus to the cell being infected, rather than killed influenza virus. HA antigen is produced using recombinant DNA technology. The HA gene is placed into baculovirus, a carrier virus that infects insect cells and is harmless to humans. Baculovirus-infected insect cells produce HA, which scientists harvest and purify from cell culture for inclusion in the vaccine.
Read more about Types of Vaccines.
Adjuvants Used in U.S. Vaccines
Alum, which is composed of aluminum salts, was the first vaccine adjuvant to be widely used in the United States. It has been used for more than 70 years. Alum is included in many U.S. vaccines, including those that prevent hepatitis B, human papillomavirus (HPV), and pneumococcus infections.
Alum was the only vaccine adjuvant in use in the United States until 2009, when the Food and Drug Administration (FDA) approved Cervarix, an HPV vaccine that contains an adjuvant called AS04. This adjuvant is a combination of alum and monophosphoryl lipid A (MPL), an immune-stimulating lipid (fat). In 2013, FDA approved the inclusion of another combination adjuvant, AS03, in the pandemic H5N1 influenza vaccine. Currently, this vaccine is included in the U.S. vaccine stockpile but is not commercially available. AS03 is an oil-in-water emulsion that is similar to MF59, an adjuvant that has been used for many years in licensed flu vaccines in more than 30 countries outside the United States. Scientists continue to develop novel antigen-adjuvant combinations.