Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine
Jake S. O’Donnell, Ariel Isaacs, Virginie Jakob, Célia Lebas, James Barnes, Patrick C. Reading, Paul R. Young, Daniel Watterson, Patrice Dubois, Nicolas Collin, Keith J. Chappell
Abstract
Various chemical adjuvants are available to augment immune responses to non-replicative, subunit vaccines. Optimized adjuvant selection can ensure that vaccine-induced immune responses protect against the diversity of pathogen-associated infection routes, mechanisms of infectious spread, and pathways of immune evasion. In this study, we compare the immune response of mice to a subunit vaccine of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) spike protein, stabilized in its prefusion conformation by a proprietary molecular clamp (MERS SClamp) alone or formulated with one of six adjuvants: either ( i ) aluminium hydroxide, ( ii ) SWE, a squalene-in-water emulsion, ( iii ) SQ, a squalene-in-water emulsion containing QS21 saponin, ( iv ) SMQ, a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D-6-acyl Phosphorylated HexaAcyl Disaccharide (3D6AP); ( v ) LQ, neutral liposomes containing cholesterol, 1.2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and QS21, ( vi ) or LMQ, neutral liposomes containing cholesterol, DOPC, QS21, and 3D6AP. All adjuvanted formulations induced elevated antibody titers which where greatest for QS21-containing formulations. These had elevated neutralization capacity and induced higher frequencies of IFN Ɣ and IL-2-producing CD4 + and CD8 + T cells. Additionally, LMQ-containing formulations skewed the antibody response towards IgG2b/c isotypes, allowing for antibody-dependent cellular cytotoxicity. This study highlights the utility of side-by-side adjuvant comparisons in vaccine development.