“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

Abstract

Emulsion adjuvants such as MF59 and AS03 have been used for more than two decades as key components of licensed vaccines, with over 100 million doses administered to diverse populations in more than 30 countries. Substantial clinical experience of effectiveness and a well-established safety profile, along with the ease of manufacturing have established emulsion adjuvants as one of the leading platforms for the development of pandemic vaccines. Emulsion adjuvants allow for antigen dose sparing, more rapid immune responses, and enhanced quality and quantity of adaptive immune responses. The mechanisms of enhancement of immune responses are well defined and typically characterized by the creation of an “immunocompetent environment” at the site of injection, followed by the induction of strong and long-lasting germinal center responses in the draining lymph nodes. As a result, emulsion adjuvants induce distinct immunological responses, with a mixed Th1/Th2 T cell response, long-lived plasma cells, an expanded repertoire of memory B cells, and high titers of cross-neutralizing polyfunctional antibodies against viral variants. Because of these various properties, emulsion adjuvants were included in pandemic influenza vaccines deployed during the 2009 H1N1 influenza pandemic, are still included in seasonal influenza vaccines, and are currently at the forefront of the development of vaccines against emerging SARS-CoV-2 pandemic variants. Here, we comprehensively review emulsion adjuvants, discuss their mechanism of action, and highlight their profile as a benchmark for the development of additional vaccine adjuvants and as a valuable tool to allow further investigations of the general principles of human immunity.

Using Dual Toll-like Receptor Agonism to Drive Th1-Biased Response in a Squalene- and α-Tocopherol-Containing Emulsion for a More Effective SARS-CoV-2 Vaccine

“…For nanoparticle vaccines, particle size is critical to the vaccine’s efficacy [ 56 ]. Size partially controls the particle uptake by innate cells [ 57 ] and the access to resident T and B cells by trafficking to the DLN via lymphatic vessels [ 42 ]. For emulsions, MF59™ with a droplet size of 160 nm has a more potent adjuvant effect than similar emulsions with a 90 or 20 nm droplet size [ 58 ], though the reason has not been elucidated.…”

“…An emulsion system containing 2.5% v / v squalene, 2.5% v / v DL-α-tocopherol, and 0.96% v / v Tween-80 in DPBS with a pH of 6.8 was chosen as the emulsion vehicle for this study, due to the success of AS03™ in other vaccines [ 42 ] and its continued testing for use as an adjuvant in a SARS-CoV-2 vaccine [ 17 ]. The commercially available AddaS03™ is a research-grade equivalent of AS03™ and also thoroughly researched.…”

Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2

“…Despite IFA lacks the mycobacterial component and causes less granuloma formation and pain than CFA, its use in preclinical studies has been replaced by less toxic W/O adjuvants, such as Montanide ISA™ 51 and 720 ( 117 ). Besides, newer squalene-based oil-in-water emulsified adjuvants, such as AS03 and MF59, are used in licensed human vaccines, as they are more readily metabolizable, less toxic, and better characterized ( 118 – 120 ). Then, a perspective in our laboratory is to explore the serum and mucosal antibody responses against recombinant proteins, using the newer adjuvants already mentioned and the combined s.c.-i.n.…”

The role of cell-mediated immunity against influenza and its implications for vaccine evaluation

“…The first novel type of adjuvant authorized for widespread use in influenza vaccines were oil-in-water (o/w) emulsions ( 142 ). These achieve a superior immune response post-vaccination by releasing specific cytokines like IL-5 and IL-8 at the site of injection which increase antigen uptake by APCs and induce a mixed Th1/Th2-oriented immune response ( 143 ). Three o/w emulsions that have already been investigated for use in commercial influenza vaccines are AS03 (GlaxoSmithKline; GSK), MF59 (Novartis), and AF03 (Sanofi Pasteur).…”