Properties and prospects of adjuvants in influenza vaccination - messy precipitates or blessed opportunities?

Abstract

Influenza is a major challenge to healthcare systems world-wide. While prophylactic vaccination is largely efficient, long-lasting immunity has not been achieved in immunized populations, at least in part due to the challenges arising from the antigen variation between strains of influenza A virus as a consequence of genetic drift and shift. From progress in our understanding of the immune system, the mode-of-action of vaccines can be divided into the stimulation of the adaptive system through inclusion of appropriate vaccine antigens and of the innate immune system by the addition of adjuvant to the vaccine formulation. A shared property of many vaccine adjuvants is found in their nature of water-insoluble precipitates, for instance the particulate material made from aluminum salts. Previously, it was thought that embedding of vaccine antigens in these materials provided a “depot” of antigens enabling a long exposure of the immune system to the antigen. However, more recent work points to a role of particulate adjuvants in stimulating cellular parts of the innate immune system. Here, we briefly outline the infectious medicine and immune biology of influenza virus infection and procedures to provide sufficient and stably available amounts of vaccine antigen. This is followed by presentation of the many roles of adjuvants, which involve humoral factors of innate immunity, notably complement. In a perspective of the ultrastructural properties of these humoral factors, it becomes possible to rationalize why these insoluble precipitates or emulsions are such a provocation of the immune system. We propose that the biophysics of particulate material may hold opportunities that could aid the development of more efficient influenza vaccines.

Structural Immunology of Complement Receptors 3 and 4

“…Finally, it is well-known that receptor-mediated phagocytosis requires a particle size of about 50 nm, which is a hard-to-reach dimension limit by applying soluble antigens. Taken together, this evidence suggests that a valuable direction of optimizing vaccine adjuvants would include a closer examination of CR3 and CR4 in this context ( 171 ).…”

“…From what we now know of the protein binding properties of CR4, it is possible to ask the question if CR4 already is a part of vaccine responses. Jalilian et al reviewed the use of adjuvants, mainly in influenza vaccination ( 171 ). In spite of some adjuvant formulations having been used for almost a 100 years, we know surprisingly little about their therapeutic effects.…”

Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate

“…Their mechanisms of adjuvanticity can be categorized accordingly to the criteria of O'Hagan and Valiante [2], which classifies them depending on their delivery system and their immunopotentiation. However, few adjuvants are currently licensed [3][4][5] and a long delay exists in licensing new types. This is creating inconvenience for novel emerging vaccines, mainly since they cannot utilize novel adjuvants focused on exploring novel strategies, such as generating also robust cell-mediated immune (CMI) responses [6][7][8].…”

Vaccines in the Prevention of Viral Pneumonia

“…Adjuvants augment the host's immune response to vaccination, normally by providing a collateral 'danger' signal via the innate immune system and thus boosting the protective acquired immune response. They enhance immunological memory, allowing greater optimised antigen presentation 9 . Examples of adjuvants include alum (aluminum salts), virosomes, MP59 and AS03.…”