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.

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 IFNƔ 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