Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice

Wørzner, Katharina; Sheward, Daniel J.; Schmidt, S.; Hanke, Leo; Zimmermann, Julie; McInerney, Gerald M.; Hedestam, Gunilla B. Karlsson; Murrell, Ben; Christensen, Dennis; Pedersen, Gabriel Kristian

doi:10.1016/j.ebiom.2020.103197

Cited by 38 publications

(36 citation statements)

References 61 publications

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“…The finding confirmed that CAF01 induced a higher level of B, Th, and CD4 + T cells than alum [ 108 ]. In a similar study, while CAF01 induced higher titer of IFN-γ and IL-17, alum adjuvanted vaccines skewed toward IL-5, IL-10, and IL-13 [ 108 ]. Studies confirmed that pre-fusion stabilized spike protein (S-2P), S1, and RBD based subunit vaccines produced NA regardless of adjuvants [ 108 , 109 ].…”

Section: Body Of the Reviewsupporting

confidence: 75%

“…Cationic adjuvant formulations (CAF01) are a liposome adjuvant containing a cocktail of dimethyldioctadecyl ammonium bromide (DDA) as a delivery vehicle and synthetic mycobacterial cord factor as an immunomodulator. Worzner et al [ 108 ] evaluated the efficacy of alum, squalene oil in water emulsion system (SE), and CAF01 and spike protein antigen in mice. The finding confirmed that CAF01 induced a higher level of B, Th, and CD4 + T cells than alum [ 108 ].…”

Section: Body Of the Reviewmentioning

confidence: 99%

“…Worzner et al [ 108 ] evaluated the efficacy of alum, squalene oil in water emulsion system (SE), and CAF01 and spike protein antigen in mice. The finding confirmed that CAF01 induced a higher level of B, Th, and CD4 + T cells than alum [ 108 ]. In a similar study, while CAF01 induced higher titer of IFN-γ and IL-17, alum adjuvanted vaccines skewed toward IL-5, IL-10, and IL-13 [ 108 ].…”

Section: Body Of the Reviewmentioning

confidence: 99%

“…In a similar study, while CAF01 induced higher titer of IFN-γ and IL-17, alum adjuvanted vaccines skewed toward IL-5, IL-10, and IL-13 [ 108 ]. Studies confirmed that pre-fusion stabilized spike protein (S-2P), S1, and RBD based subunit vaccines produced NA regardless of adjuvants [ 108 , 109 ]. A study using S1 as the antigen evaluated the titer of neutralizing antibody and found that CoVaccine adjuvanted S1 protein subunit vaccines produced more neutralizing IgG antibodies than aluminum adjuvanted S1 protein vaccines [ 109 ].…”

Section: Body Of the Reviewmentioning

confidence: 99%

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SARS-CoV-2 subunit vaccine adjuvants and their signaling pathways

Mekonnen

Mengist

Jin

2021

Expert Review of Vaccines

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Introduction: Vaccines are the agreed upon weapon against the COVID-19 pandemic. This review discusses about COVID-19 subunit vaccines adjuvants and their signaling pathways, which could provide a glimpse into the selection of appropriate adjuvants for prospective vaccine development studies. Areas covered: In the introduction, a brief background about the SARS-CoV-2 pandemic, the vaccine development race and classes of vaccine adjuvants were provided. . The antigen, trial stage, and types of adjuvants were extracted from the included articles and thun assimilated. Finally, the pattern recognition receptors (PRRs), their classes, cognate adjuvants, and potential signaling pathways were comprehended. Expert opinion: Adjuvants are unsung heroes of subunit vaccines. The in silico studies are very vital in avoiding several costly trial errors and save much work times. The majority of the (pre)clinical studies are promising. It is encouraging that most of the selected adjuvants are novel. Much emphasis must be paid to the optimal paring of antigen-adjuvant-PRRs for obtaining the desired vaccine effect. A good subunit vaccine/adjuvant is one that has high efficacy, safety, dose sparing, and rapid seroconversion rate and broad spectrum of immune response. In the years to come, COVID-19 adjuvanted subunit vaccines are expected to have superior utility than any other vaccines for various reasons.

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Section: Body Of the Reviewsupporting

confidence: 75%

Section: Body Of the Reviewmentioning

confidence: 99%

Section: Body Of the Reviewmentioning

confidence: 99%

Section: Body Of the Reviewmentioning

confidence: 99%

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SARS-CoV-2 subunit vaccine adjuvants and their signaling pathways

Mekonnen

Mengist

Jin

2021

Expert Review of Vaccines

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“…Wørzne et al reported that a single immunization of mice with the SARS-CoV-2 spike protein together with the adjuvant CAF01 significantly enhanced spike-specific CD4 + T H responses, producing IFN-γ and IL-17, compared to other adjuvants, such as squalene emulsion (SE) and aluminum hydroxide. By contrast, the antibody responses against the spike receptor binding domain (RBD) was similar for all adjuvants [102]. Vaccines against hepatitis virus E mainly target the structural capsid protein open-reading-frame-2 (ORF-2) of the virus.…”

Section: Liposomes As Adjuvants In Vaccine Formulationsmentioning

confidence: 99%

Nano-Microparticle Platforms in Developing Next-Generation Vaccines

et al. 2021

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The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8+ T-cell response. In contrast, next-generation nano/microparticle-based vaccines offer several advantages over traditional ones because they can induce a more potent CD8+ T-cell response and, at the same time, are ideal carriers for proteins, adjuvants, and nucleic acids. The fact that these nanocarriers can be loaded with molecules able to modulate the immune response by inducing different effector functions and regulatory activities makes them ideal tools for inverse vaccination, whose goal is to shut down the immune response in autoimmune diseases. Poly (lactic-co-glycolic acid) (PLGA) and liposomes are biocompatible materials approved by the Food and Drug Administration (FDA) for clinical use and are, therefore, suitable for nanoparticle-based vaccines. Recently, another candidate platform for innovative vaccines based on extracellular vesicles (EVs) has been shown to efficiently co-deliver antigens and adjuvants. This review will discuss the potential use of PLGA-NPs, liposomes, and EVs as carriers of peptides, adjuvants, mRNA, and DNA for the development of next-generation vaccines against endemic and emerging viruses in light of the recent COVID-19 pandemic.

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Pathogen‐Mimicking Nanoparticles Based on Rigid Nanomaterials as an Efficient Subunit Vaccine Delivery System for Intranasal Immunization

Wan,

Deng,

Huang

et al. 2024

Adv Healthcare Materials

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Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan–catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS‐CoV‐2 spike protein receptor‐binding domain (RBD) and toll‐like receptor (TLR)9 agonist unmethylated cytosine‐guanine (CpG) motif, forming uniform virus‐like nanoparticles (Ssp‐Chic‐RBD‐CpG) via electrostatic and covalent interactions. Ssp‐Chic‐RBD‐CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92‐fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C‐C motif) ligand 20 (CCL20)‐driven DCs recruitment and maturation by Ssp‐Chic‐RBD‐CpG are evidenced by a cell co‐culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF‐κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein‐based subunit vaccines as well when intranasal administration is needed.

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Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice

Cited by 38 publications

References 61 publications

SARS-CoV-2 subunit vaccine adjuvants and their signaling pathways

SARS-CoV-2 subunit vaccine adjuvants and their signaling pathways

Nano-Microparticle Platforms in Developing Next-Generation Vaccines

Pathogen‐Mimicking Nanoparticles Based on Rigid Nanomaterials as an Efficient Subunit Vaccine Delivery System for Intranasal Immunization

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