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

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.

Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms

“… 20 Furthermore, SQ combined with MERS-CoV RBD antigen induced robust CD4 + and CD8 + T cell Th1-type response, comparable with LMQ. 54 These data suggest that the ability of adjuvants to strongly activate NLRP3 may be a valuable mechanism for vaccines targeting CD8 + T cell immunity, such as HIV vaccine candidates.…”

“…Adjuvants used in this study (SQ, SMQ, LQ and LMQ) were manufactured at the Vaccine Formulation Institute as described previously. 54 Briefly, SQ adjuvant was prepared by combining squalene-in-water emulsion containing cholesterol (Merck-Sigma, USA) with QS-21 in solution (Desert King International, USA). SMQ was prepared in a similar fashion with the emulsion containing both cholesterol and synthetic TLR4 ligand 3D-6-acyl-PHAD (3D6AP) (Merck-Avanti, USA).…”

Difference in respiratory syncytial virus-specific Fc-mediated antibody effector functions between children and adults

“…Additionally, our study yielded novel insights into the differences between children and adults in functional antibody responses, which warrant further investigations to define their role in protection, taking into account potential differences between risk groups which might require a tailored approach to vaccination. Different vaccine adjuvants have previously been shown to steer the production of antibodies with different functionalities [ 78 , 79 ]. While this provides opportunities for rational vaccine design, more research is needed to fully understand the factors underlying the regulation of antibody quality.…”

Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice

“…The SWE adjuvant (squalene-in-water emulsion) was co-developed by the Vaccine Formulation Institute (Plan-les-Ouates, Switzerland) and Seppic (La Garenne Colombes, France) and is available at GMP grade (Sepivac SWE™) under an open-access model. The SQ, SMQ, LQ, and LMQ adjuvant formulations were manufactured at the Vaccine Formulation Institute (VFI) [ 16 ].…”

“…We also compared the effects of different adjuvants on monomeric (R_M) and trimeric (R_T) stabilized RBD. The adjuvants used were aluminum hydroxide (Al(OH) 3 ), SWE, SQ (a squalene-in-water emulsion containing QS21 saponin), SMQ (a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D(6acyl)-PHAD (3D6AP)), LQ (neutral liposomes containing cholesterol, 1.2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and QS21), and LMQ (neutral liposomes containing cholesterol, DOPC, QS21, and 3D6AP) [ 16 ].…”