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

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

doi:10.3389/fimmu.2022.976968

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

Front Immunol. 2022 Sep 2:13:976968. doi: 10.3389/fimmu.2022.976968. eCollection 2022.

Authors

Jake S O'Donnell^{1

2}, Ariel Isaacs^{1

2}, Virginie Jakob³, Celia Lebas³, James B Barnes⁴, Patrick C Reading^{4

5}, Paul R Young^{1

2

6}, Daniel Watterson^{1

2

6}, Patrice M Dubois³, Nicolas Collin³, Keith J Chappell^{1

2

6}

Affiliations

¹ The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.
² The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
³ Vaccine Formulation Institute, Geneva, Switzerland.
⁴ The WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁵ Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁶ Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, QLD, Australia.

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.

Keywords: MERS; T cell; adjuvant; antibody; vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
Adjuvants, Pharmaceutic
Aluminum Hydroxide
Animals
CD8-Positive T-Lymphocytes
Disaccharides
Emulsions
Immunoglobulin G
Interleukin-2
Liposomes
Mice
Phosphorylcholine
Saponins* / pharmacology
Spike Glycoprotein, Coronavirus
Squalene
Toll-Like Receptor 4*
Vaccines, Subunit
Water

Substances

Adjuvants, Immunologic
Adjuvants, Pharmaceutic
Disaccharides
Emulsions
Immunoglobulin G
Interleukin-2
Liposomes
Saponins
Spike Glycoprotein, Coronavirus
Toll-Like Receptor 4
Vaccines, Subunit
Water
Phosphorylcholine
Aluminum Hydroxide
Squalene