| Summary: | Vaccines have evolved from using attenuated viruses beginning in 1935, to using inactivated viruses, toxoids and now to using subunit and recombinant proteins. Subunit proteins use viral antigens (fragments) to generate protective immunity, and as such are less immunogenic compared to attenuated or inactivated (whole) viral vaccines. As a result, adjuvants are added to subunit vaccines, to improve their effectiveness by enhancing and sustaining immune responses, reducing the
dose of antigen needed, enhancing the breadth of the immune response, increasing the immunological memory associated with the adaptive immune system, and decreasing the frequency of vaccination. Adjuvants developed to enhance immune responses include aluminum hydroxide compounds (alum), emulsions, virosomes, liposomes, and ISCOMs. In the last few decades considerable attention has been focused on lipid-based adjuvants for use in vaccines - for example, squalene oil-in-water emulsions as
adjuvants have been extensively studied. Currently two emulsion adjuvants are added to commercially marketed influenza vaccines: MF59 and AS03 with many more in pre-clinical and clinical studies - GLA-SE, WEC50, AF03, AF04, etc. Emulsion adjuvants promote or enhance T-cell responses, which are typically absent after recombinant protein immunization, and have been used successfully for flu prevention in a diverse group of patients for flu, from pediatric to geriatric and from healthy
individuals to immune-compromised individuals. Even though adjuvanted flu vaccines are commercially successful, the mechanism of action of these added agents is not clearly understood. This lack of understanding is a key hindrance in adjuvant development, which in turn holds back vaccine development in general.
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