Safety and Mechanism of Action of Licensed Vaccine Adjuvants.

Vaccines are some of the most effective tools for the prevention of infectious diseases. Adjuvants are included in vaccines for a variety of reasons: to increase the breadth of response, to lower antigen dose, to overcome limited immune response in some populations, or to enable complex combination vaccines. This study aims to review the safety of licensed vaccine adjuvants and describe their mechanism of action. Potential publications for inclusion were identified through a direct search of PubMed/Medline database. Results of online literature searches were supplemented by relevant papers cited in published studies along with the authors’ knowledge of published studies. To date, there are 5 licensed vaccine adjuvants in US and Europe: Aluminum salts (EU, US), MF59 (EU), AS03 (EU), AS04 (EU, US), and virosomes (EU). AS03 is not available as an adjuvant in other vaccines but included within the US government’s National Stockpile. All vaccines that contain these adjuvants have been proven safe in clinical trials and post-marketing studies, with the exception of the AS03, for which the rare events of narcolepsy have been reported in some countries. Every adjuvant has a complex and often multifactorial immunological mechanism, usually poorly understood in vivo. The safety profile of an adjuvant, including the actual and hypothetical risks, is a critical component that can speed up or impede adjuvant development. The increasing understanding in adjuvant sciences is fundamental to the further development of new adjuvants.

Safety and Mechanism of Action of Licensed Vaccine Adjuvants.

Vaccines are some of the most effective tools for the prevention of infectious diseases. Adjuvants are included in vaccines for a variety of reasons: to increase the breadth of response, to lower antigen dose, to overcome limited immune response in some populations, or to enable complex combination vaccines. This study aims to review the safety of licensed vaccine adjuvants and describe their mechanism of action. Potential publications for inclusion were identified through a direct search of PubMed/Medline database. Results of online literature searches were supplemented by relevant papers cited in published studies along with the authors’ knowledge of published studies. To date, there are 5 licensed vaccine adjuvants in US and Europe: Aluminum salts (EU, US), MF59 (EU), AS03 (EU), AS04 (EU, US), and virosomes (EU). AS03 is not available as an adjuvant in other vaccines but included within the US government’s National Stockpile. All vaccines that contain these adjuvants have been proven safe in clinical trials and post-marketing studies, with the exception of the AS03, for which the rare events of narcolepsy have been reported in some countries. Every adjuvant has a complex and often multifactorial immunological mechanism, usually poorly understood in vivo. The safety profile of an adjuvant, including the actual and hypothetical risks, is a critical component that can speed up or impede adjuvant development. The increasing understanding in adjuvant sciences is fundamental to the further development of new adjuvants.

Virosome vaccines and their application in cancer immunotherapy

Background: An increasing number of tumor associated antigens (TAA) capable of inducing immune responses have been identified in the last two decades. Unfortunately, they are weak immunogens and require potent adjuvants to promote their immunogenicity. Virosomes, nano-lipid vesicles containing viral protein spikes, have been proven amenable for transferring antigen (Ag) to the major histocompatibility complex (MHC) class I processing pathway with the aim to prime cytotoxic T-ymphocytes (CTL) responses. Objective: This mini-review outlines the virosomes platform, ranging from virosomal preparation, their intracellular trafficking and mechanism of action. Methods: The review is directed toward an application of virosomes as a novel and potential vaccine adjuvant in active cancer immunotherapy. Results and conclusion: Virosomes have been proven to be a suitable TAA delivery carrier. Ag encapsulated inside the lumen of virosomes could be prevented from serum- and cell-associated peptidases. Virosomes also facilitated the intracellular trafficking of encapsulated Ag, in which Ag could reach the cytosol and be presented by the MHC-Class I machinery. In addition, virosomes with TAA encapsulated are amenable to be a novel tumor immunotherapeutic strategy.