AUTHOR=O’Donnell Jake S. , Isaacs Ariel , Jakob Virginie , Lebas Celia , Barnes James B. , Reading Patrick C. , Young Paul R. , Watterson Daniel , Dubois Patrice M. , Collin Nicolas , Chappell Keith J. 

TITLE=Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.976968

DOI=10.3389/fimmu.2022.976968

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>i</italic>) aluminium hydroxide, (<italic>ii</italic>) SWE, a squalene-in-water emulsion, (<italic>iii</italic>) SQ, a squalene-in-water emulsion containing QS21 saponin, (<italic>iv</italic>) SMQ, a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D-6-acyl Phosphorylated HexaAcyl Disaccharide (3D6AP); (<italic>v</italic>) LQ, neutral liposomes containing cholesterol, 1.2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and QS21, (<italic>vi</italic>) 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<sub>Ɣ</sub> and IL-2-producing CD4<sup>+</sup> and CD8<sup>+</sup> 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.</p>