CpG Oligonucleotides as Vaccine Adjuvants

Kayraklioglu, Neslihan; Horuluoglu, Begum; Klinman, Dennis M.

doi:10.1007/978-1-0716-0872-2_4

Cited by 75 publications

(76 citation statements)

References 294 publications

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“…Furthermore, Biological E has recently completed early phase (1 and 2) trials of a AH:CpG-adjuvanted SARS-CoV-2 RBD protein vaccine (trial # CTRI/2020/11/029032) which was intended for low- and middle-income countries, and are currently advancing through manufacturing and clinical development through a large-scale phase 3 trial in India ( 17 ). CpG is classified into 4 major classes, with distinct activation profiles of human cells ( 68 ). Class B CpG-1018 has been extensively evaluated in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this preprint (which this version posted May 21, 2021. ; https://doi.org/10.1101/2021.05.20.444848 doi: bioRxiv preprint currently advancing through manufacturing and clinical development through a large-scale phase trial in India (17). CpG is classified into major classes, with distinct activation profiles of human cells (68). Class B CpG-1018 has been extensively evaluated in clinical trials.…”

Section: ± 4)mentioning

confidence: 99%

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Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity

McGrath

Haupt

Seo

et al. 2021

Preprint

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Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic especially for low- and middle-income countries. While vaccines against SARS-CoV-2 based on mRNA and adenoviral-vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are needed to meet global demand. In this context, protein subunit vaccines formulated with appropriate adjuvants represent a promising approach to address this urgent need. Receptor-binding domain (RBD) is a key target of neutralizing antibodies (Abs) but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists, including those activating STING, TLR3, TLR4 and TLR9, alone or formulated with aluminum hydroxide (AH), and benchmarked them to AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that the AH and CpG adjuvant formulation (AH:CpG) demonstrated the highest enhancement of anti-RBD neutralizing Ab titers in both age groups (~80-fold over AH), and protected aged mice from the SARS-CoV-2 challenge. Notably, AH:CpG-adjuvanted RBD vaccine elicited neutralizing Abs against both wild-type SARS-CoV-2 and B.1.351 variant at serum concentrations comparable to those induced by the authorized mRNA BNT162b2 vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and synergistically enhanced cytokine and chemokine production in human young adult and elderly mononuclear cells. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.

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Section: Discussionmentioning

confidence: 99%

Section: ± 4)mentioning

confidence: 99%

Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity

McGrath

Haupt

Seo

et al. 2021

Preprint

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“…Such formulations should promote optimum immune responses and immunological memory (150). Suitable targets would be TLR3, TL7, TLR8, or TLR9 (151)(152)(153).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

Stoy

2021

Front. Immunol.

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Interleukin-1 receptor-associated kinase 4 (IRAK4) and interferon regulatory factor 5 (IRF5) lie sequentially on a signaling pathway activated by ligands of the IL-1 receptor and/or multiple TLRs located either on plasma or endosomal membranes. Activated IRF5, in conjunction with other synergistic transcription factors, notably NF-κB, is crucially required for the production of proinflammatory cytokines in the innate immune response to microbial infection. The IRAK4-IRF5 axis could therefore have a major role in the induction of the signature cytokines and chemokines of the hyperinflammatory state associated with severe morbidity and mortality in COVID-19. Here a case is made for considering IRAK4 or IRF5 inhibitors as potential therapies for the “cytokine storm” of COVID-19.

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“…Our study revealed important data about the in vitro interplay between human primary mDCs and A. fumigatus antigens focusing on molecular and functional mechanisms, which in future might allow the development of immunomodulators for more effective antifungal immunotherapy. This includes additional in vitro and in vivo studies on the potential use of appropriate adjuvants for mDC activation, such as TLR ligands (e.g., Pam3CDK4 or CpG-containing oligonucleotides) ( 35 ), the combined use of mDCs and autologous pDCs ( 36 ), or the exploitation of the potential immunomodulatory effects of antifungals, especially echinocandins, on ex vivo -pulsed mDCs. Although a GMP-grade medium was used for DC culture and stimulation in this study, further standardization of the antigens and protocols for future GMP-compliant products will be needed.…”

Section: Discussionmentioning

confidence: 99%

CcpA- and Shm2-Pulsed Myeloid Dendritic Cells Induce T-Cell Activation and Enhance the Neutrophilic Oxidative Burst Response to Aspergillus fumigatus

et al. 2021

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Aspergillus fumigatus causes life-threatening opportunistic infections in immunocompromised patients. As therapeutic outcomes of invasive aspergillosis (IA) are often unsatisfactory, the development of targeted immunotherapy remains an important goal. Linking the innate and adaptive immune system, dendritic cells are pivotal in anti-Aspergillus defense and have generated interest as a potential immunotherapeutic approach in IA. While monocyte-derived dendritic cells (moDCs) require ex vivo differentiation, antigen-pulsed primary myeloid dendritic cells (mDCs) may present a more immediate platform for immunotherapy. To that end, we compared the response patterns and cellular interactions of human primary mDCs and moDCs pulsed with an A. fumigatus lysate and two A. fumigatus proteins (CcpA and Shm2) in a serum-free, GMP-compliant medium. CcpA and Shm2 triggered significant upregulation of maturation markers in mDCs and, to a lesser extent, moDCs. Furthermore, both A. fumigatus proteins elicited the release of an array of key pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-8, and CCL3 from both DC populations. Compared to moDCs, CcpA- and Shm2-pulsed mDCs exhibited greater expression of MHC class II antigens and stimulated stronger proliferation and IFN-γ secretion from autologous CD4+ and CD8+ T-cells. Moreover, supernatants of CcpA- and Shm2-pulsed mDCs significantly enhanced the oxidative burst in allogeneic neutrophils co-cultured with A. fumigatus germ tubes. Taken together, our in vitro data suggest that ex vivo CcpA- and Shm2-pulsed primary mDCs have the potential to be developed into an immunotherapeutic approach to tackle IA.

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CpG Oligonucleotides as Vaccine Adjuvants

Cited by 75 publications

References 294 publications

Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity

Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

CcpA- and Shm2-Pulsed Myeloid Dendritic Cells Induce T-Cell Activation and Enhance the Neutrophilic Oxidative Burst Response to Aspergillus fumigatus

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