Coadministration of antigen-conjugated and free CpG: Effects of in vitro and in vivo interactions in a murine model

Herbáth, Melinda; Szekeres, Zsuzsanna; Kövesdi, Dorottya; Papp, Krisztián; Erdei, Anna; Prechl, József

doi:10.1016/j.imlet.2014.02.007

Cited by 7 publications

(10 citation statements)

References 33 publications

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“…A variety of antigen-adjuvant co-delivery systems have been developed, including particulate vaccine formulations and soluble conjugates. [6][7][8][9][10] In soluble conjugates, the tumor antigen is directly conjugated to a vaccine adjuvant as a means for co-delivery and has been shown to induce a strong immune response. 9,11,12 However, the direct conjugation of antigen to adjuvant may obstruct both the processing of the antigen for presentation to T cells as well as the binding of the adjuvant to the target toll-like receptor (TLR) for complete activation of the APC.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity

et al. 2017

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“…Similar to previous examples, higher antibody and cellular immune responses were observed for the conjugates, with no CTL responses observed where mixtures were administered. Finally, CpG oligodeoxynucelotide (ODN) ligands for TLR9 have also been attached to protein and peptide vaccines, once again demonstrating the production of more potent antibody (Herbath et al, 2014) and CTL responses in mice (Heit et al, 2003; Datta et al, 2004). The use of CpG‐ODN as an adjuvant in humans, however, may prove less effective than in mice due to reduced expression of TLR9 by human DC subsets (Kastenmuller et al, 2014).…”

Section: Development Of Subunit Vaccine Formulationsmentioning

confidence: 99%

Progress in Vaccine Development

Moyle

2015

CP Microbiology

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Vaccination has a proven record as one of the most effective medical approaches to prevent the spread of infectious diseases. Traditional vaccine approaches involve the administration of whole killed or weakened microorganisms to stimulate protective immune responses. Such approaches deliver many microbial components, some of which contribute to protective immunity, and assist in guiding the type of immune response that is elicited. Despite their impeccable record, these approaches have failed to yield vaccines for many important infectious organisms. This has prompted a move towards more defined vaccines (‘subunit vaccines’), where individual protective components are administered. This unit provides an overview of the components that are used for the development of modern vaccines including: an introduction to different vaccine types (whole organism, protein/peptide, polysaccharide, conjugate, and DNA vaccines); techniques for identifying subunit antigens; vaccine delivery systems; and immunostimulatory agents (‘adjuvants’), which are fundamental for the development of effective subunit vaccines. © 2015 by John Wiley & Sons, Inc.

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“… 12 − 14 Co-delivery of an antigen with CpG has been shown in vitro and in vivo to enhance antigen presentation to T-cells, the activation and differentiation of T-cells into T H 1 and cytotoxic T lymphocytes (CTL), and the cytotoxicity of effector T-cells compared with delivery as a mixture. 2 , 4 , 5 , 8 , 15 , 16 The enhanced immune response observed when co-delivering an antigen and CpG is believed to be due to their simultaneous internalization by an APC. When delivered as a mixture, only one of the two agents might be internalized, leading to either an activated APC that does not present the antigen to T-cells or an APC that may present the antigen, however, without being fully activated, thereby not being able to induce a full T-cell response.…”

Section: Introductionmentioning

confidence: 99%

“…The generation of a cellular T-helper (T H ) 1 immune response is important for the development of vaccination strategies. The co-delivery of an adjuvant and an antigen to antigen-presenting cells (APCs) has been shown to induce strong cellular immune responses and, therefore, has the potential to develop enhanced immunotherapies. , Co-delivery of an antigen and an adjuvant for inducing cellular immune responses has been achieved by formulating the antigen and adjuvant into or onto a particle − or by directly conjugating the antigen and adjuvant to each other. − …”

Section: Introductionmentioning

confidence: 99%

Comparative Study of 5′- and 3′-Linked CpG–Antigen Conjugates for the Induction of Cellular Immune Responses

2017

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Conjugation of CpG to an antigen induces a stronger immune response compared to that of the mixture. This study compares the in vitro immunostimulatory activity of CpG conjugated via either its 5′ or 3′ end to the model antigen ovalbumin (OVA). CpG modified with an amine at either the 5′ or 3′ end was conjugated to OVA via a stable bis-aryl hydrazone bond. Similar levels of CpG conjugation to OVA were observed for both conjugates on the basis of the absorbance at 360 nm for the formation of the bis-aryl hydrazone bond, which determined 2.8 ± 0.3 CpGs linked per OVA. Both the 5′ and 3′ CpG–OVA conjugates had similar size-exclusion chromatography elution profiles. The immunostimulatory properties of the conjugates were determined by dendritic cells (DCs) and T-cells isolated from mice. The activation of DCs was determined by the upregulation of activation markers CD86 and CD40. T-cells were co-cultured with stimulated DCs, and the immunogenicity was determined by measuring T-cell proliferation and interferon γ production. Both the CpG 5′- and 3′-linked conjugates induced the same level (p > 0.5) of DC activation markers, which were significantly higher than those of the untreated control. Similarly, T-cell assays showed no significant difference (p > 0.5) between the 5′ and 3′ conjugates with respect to T-cell proliferation and interferon γ production. The 5′ and 3′ conjugates induced T-cell activation significantly higher than the mixture of CpG and OVA. This study showed that the end at which CpG is conjugated to an antigen has no influence on the generation of a T-cell-based immune response in vitro.

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Coadministration of antigen-conjugated and free CpG: Effects of in vitro and in vivo interactions in a murine model

Cited by 7 publications

References 33 publications

Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity

Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity

Progress in Vaccine Development

Comparative Study of 5′- and 3′-Linked CpG–Antigen Conjugates for the Induction of Cellular Immune Responses

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