Blueprints of Signaling Interactions between Pattern Recognition Receptors: Implications for the Design of Vaccine Adjuvants

Timmermans, Kim; Plantinga, Theo S.; Kox, Matthijs; Vaneker, Michiel; Scheffer, Gert Jan; Adema, Gosse J.; Joosten, Leo A. B.; Netea, Mihai G.

doi:10.1128/cvi.00703-12

Cited by 40 publications

(32 citation statements)

References 31 publications

(50 reference statements)

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“…These techniques target a specific PRR or a limited population of PRRs (32,34). However, activation of a broader range of PRRs resulting from release of damage-associated molecular patterns (DAMPs) during natural lytic viral infection is able to produce a more robust immune response (31,33,(35)(36)(37).…”

mentioning

confidence: 99%

“…Furthermore, they are inexpensive, can be easily manufactured, and can be stored for long periods (28,29), making them ideal for use in developing countries where the need for an effective HCV vaccine is greatest. Until now, strategies to enhance the immunogenicity of DNA vaccines have focused on encoding agonists of pathogen recognition receptors (PRRs), including Toll-like receptor (TLR) and NOD-like receptor agonists, or coinjection with TLR agonists such as poly(I·C) (30)(31)(32)(33). These techniques target a specific PRR or a limited population of PRRs (32,34).…”

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confidence: 99%

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A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

Gummow

et al. 2015

J Virol

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There are 3 to 4 million new hepatitis C virus (HCV) infections annually around the world, but no vaccine is available. Robust T-cell mediated responses are necessary for effective clearance of the virus, and DNA vaccines result in a cell-mediated bias. Adjuvants are often required for effective vaccination, but during natural lytic viral infections damage-associated molecular patterns (DAMPs) are released, which act as natural adjuvants. Hence, a vaccine that induces cell necrosis and releases DAMPs will result in cell-mediated immunity (CMI), similar to that resulting from natural lytic viral infection. We have generated a DNA vaccine with the ability to elicit strong CMI against the HCV nonstructural (NS) proteins (3, 4A, 4B, and 5B) by encoding a cytolytic protein, perforin (PRF), and the antigens on a single plasmid. We examined the efficacy of the vaccines in C57BL/6 mice, as determined by gamma interferon enzyme-linked immunosorbent spot assay, cell proliferation studies, and intracellular cytokine production. Initially, we showed that encoding the NS4A protein in a vaccine which encoded only NS3 reduced the immunogenicity of NS3, whereas including PRF increased NS3 immunogenicity. In contrast, the inclusion of NS4A increased the immunogenicity of the NS3, NS4B, andNS5B proteins, when encoded in a DNA vaccine that also encoded PRF. Finally, vaccines that also encoded PRF elicited similar levels of CMI against each protein after vaccination with DNA encoding NS3, NS4A, NS4B, and NS5B compared to mice vaccinated with DNA encoding only NS3 or NS4B/5B. Thus, we have developed a promising "multiantigen" vaccine that elicits robust CMI. IMPORTANCESince their development, vaccines have reduced the global burden of disease. One strategy for vaccine development is to use commercially viable DNA technology, which has the potential to generate robust immune responses. Hepatitis C virus causes chronic liver infection and is a leading cause of liver cancer. To date, no vaccine is currently available, and treatment is costly and often results in side effects, limiting the number of patients who are treated. Despite recent advances in treatment, prevention remains the key to efficient control and elimination of this virus. Here, we describe a novel DNA vaccine against hepatitis C virus that is capable of inducing robust cell-mediated immune responses in mice and is a promising vaccine candidate for humans. G lobal efforts to generate an effective vaccine for hepatitis C virus (HCV) have been hampered, since correlates of sterilizing immunity have not been identified and traditional vaccine strategies have proved to be ineffective (1). Approximately 230 million individuals are infected, many of whom will develop serious liver disease, and since current treatment is costly and often results in serious side effects, this has limited the number of patients who are treated (2, 3). Much of the global effort to develop an effective HCV vaccine/treatment has been directed toward genotype 1 (gt1) (4, 5); however, gt3 is ...

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confidence: 99%

mentioning

confidence: 99%

A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

Gummow

et al. 2015

J Virol

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“…Triggering specific combinations of PRRs in DCs can induce synergistic production of cytokines, which can result in enhanced T-cell responses (Th1, Th2 and Th17) [65][66][67] and/or reversal of the immunosuppressive action of regulatory T cells (T reg ) [68][69][70]. The inclu- increase in the manufacturing capacity and offers a potential for greater distribution of the given vaccine.…”

Section: Nod-like Receptors (Nlrs) C-type Lectin Receptors (Clrs) Anmentioning

confidence: 98%

Poly(Lactic Acid) and Poly(Lactic- Co -Glycolic Acid) Particles as Versatile Carrier Platforms for Vaccine Delivery

Pavot

Berthet

Rességuier

et al. 2014

Nanomedicine (Lond.)

106

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The development of safe and effective vaccines for cancer and infectious diseases remains a major goal in public health. Over the last two decades, controlled release of vaccine antigens and immunostimulant molecules has been achieved using nanometer or micron-sized delivery vehicles synthesized using biodegradable polymers. In addition to achieving a depot effect, enhanced vaccine efficacy using such delivery vehicles has been attributed to efficient targeting of antigen presenting cells such as dendritic cells. Biodegradable and biocompatible poly(lactic acid) and poly(lactic-co-glycolic acid) polymers belong to one such family of polymers that have been a popular choice of material used in the design of these delivery vehicles. This review summarizes research findings from ourselves and others highlighting the promise of poly(lactic acid)- and poly(lactic-co-glycolic acid)-based vaccine carriers in enhancing immune responses.

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“…Reseptor PRRs yang lain, Toll like Receptors (TLR), Nucleotide Binding Oligomerization Domain Proteins (NOD), RNA helicases seperti Retinoic Acid Induce-Ible Gen 1 (RIG-1) atau MDA5, lectin tipe C mampu menghambat respon sinyal intraseluler untuk mengaktifkan gen yang memproduksi sitokin. Kombinasi TLR2 dan NOD2, TLR5 dan NOD2, TLR5 dan TLR3 serta TLR5 dan TLR 9 menunjukkan sinergisme yang baik dalam memproduksi sitokin sedangkan kombinasi TLR4 dan TLR2, TLR4 dan Dectin-1, TLR2 dan TLR9 serta TLR3 dan TLR2 menghambat produksi sitokin (Timmermans et al 2013).…”

Section: Pattern Recognition Receptors Pada Sistem Kekebalan Bawaan Uunclassified

“…Sitokin adalah mediator peptida yang disekresikan oleh sel hematopoietic atau non-hematopoietic yang dapat menghambat atau meningkatkan proliferasi, diferensiasi, aktivasi dan pergerakan sel, serta berperan penting dalam kekebalan dan produksi sitokin lainnya (Timmermans et al 2013). Respon yang ditimbulkan oleh sitokin tergantung pada jenis sitokin dan sel target.…”

Section: Sitokinunclassified

Cytokines Disregulation in Birds and Mammals Infected by Avian Influenza Virus

Hewajuli¹,

Dharmayanti²

2016

WARTAZOA

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Blueprints of Signaling Interactions between Pattern Recognition Receptors: Implications for the Design of Vaccine Adjuvants

Cited by 40 publications

References 31 publications

A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

Poly(Lactic Acid) and Poly(Lactic- Co -Glycolic Acid) Particles as Versatile Carrier Platforms for Vaccine Delivery

Cytokines Disregulation in Birds and Mammals Infected by Avian Influenza Virus

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