Synthetic innate defence regulator peptide enhances in vivo immunostimulatory effects of CpG-ODN in newborn piglets

Cao, Ding; Li, Huazhou; Jiang, Zhenggu; Xu, Chenchao; Cheng, Qing; Yang, Zhaihan; Cao, Guangjun; Zhang, Linghua

doi:10.1016/j.vaccine.2010.06.103

Cited by 21 publications

(15 citation statements)

References 44 publications

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“…This sequence shares the same ancestor as the other sequences used in this study, it has relatively improved activity, and it has been employed previously as an adjuvant (15,16). We replaced two or three amino acids to produce new peptides the peptide, and the first column gives the amino acid species.…”

Section: Resultsmentioning

confidence: 99%

In Vitro and In Vivo Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method

Wang

et al. 2014

Antimicrob Agents Chemother

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cTo design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machinelearning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. The in vivo antimicrobial activity of DP7 was tested in a Staphylococcus aureus infection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of the S. aureus outer membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections.A ntimicrobial peptides (AMPs) are produced by multicellular organisms to defend against microbial infections. Along with potent antimicrobial activity, many AMPs also have the ability to enhance immunity by functioning as immunomodulators (1-3). AMPs therefore have excellent therapeutic potential, especially in light of increased drug resistance to many conventional antibiotic therapies. A number of naturally occurring peptides and synthetic derivatives have been developed or are currently in development (2, 4-6). Although AMPs vary in length, amino acid composition, and structure, they share some similarities, such as electrical charge and amphipathicity (3, 7). To determine the characteristics that are important in antimicrobial activity, bioinformatic tools and prediction methods have been developed (8), all based to some extent on the sequence similarities between peptides (9-11).To optimize the antimicrobial activity of identified AMPs and to predict novel peptide sequences, we present a machine-learning method based on the concept of an antimicrobial activity contribution score for each amino acid. Here, we consider that each amino acid in a peptide sequence possesses a different level of importance for the biological activity of that peptide, and this is represented by an assigned score. By calculation of each amino acid's contribution score, we can predict the antimicrobial activity of an AMP.To verify our results, we tested some of our designed AMPs ...

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Section: Resultsmentioning

confidence: 99%

In Vitro and In Vivo Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method

Wang

et al. 2014

Antimicrob Agents Chemother

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“…Recently, several reports had demonstrated enhanced adjuvant activities for IDRs in combination with CpG ODN [11][12][13][14]. And our recent investigation [21] also clearly showed that the combination of CpG ODN and peptide HH2 (VQLRIRVAVIRA) had good immunostimulatory functions on innate immune system for piglets. To date, there is still no information on the efficiency of CpG ODN combination with IDRs on the intestinal innate immune system when delivered to neonatal piglets.…”

Section: Introductionmentioning

confidence: 66%

“…Clinical signs and morbidity were examined daily for 14 days post challenge. The doses of CpG ODN and IDR used correspond to those previously reported by Zhang et al and Kindrachuk et al [11,20,21]. At day 3 post immunization 6 piglets per group were euthanized by bleeding under anesthesia by intravenous injection of Halothane (24 mg/kg), intestinal tissues (jejunum) and mesenteric lymph nodes (MLNs) were collected and jejunum tissue samples were stored at − 70°C until assayed by quantitative real-time PCR (qRT-PCR) sequence detection system for chemokines (IP-10, I-TAC, RANTES and MCP-1) and cytokines (IFN-γ, IL-4, TNF-α, IL-12) mRNA expression in intestinal tissues.…”

Section: Immunization Of Animalsmentioning

confidence: 84%

“…Recently, synthetic IDRs are being investigated as potential immunotherapeutic agents because of their unique combination of immunostimulatory and anti-inflammatory properties [34]. Here we had undertaken to choose HH2, whose good immunostimulatory effects were reported recently [10] and also were tested by us [21] to have optimal effects among reported IDRs. In this study, we showed that combination of CpG ODN and IDR could further enhance innate intestinal immunity compared to CpG ODN and IDR alone in newborn piglets.…”

Section: Discussionmentioning

confidence: 99%

“…Here we had undertaken to choose HH2, whose good immunostimulatory effects were reported recently [11] and also were tested by us [21] to have optimal effects among reported IDRs, and investigated whether the combination of HH2 with CpG ODN could enhance innate intestinal immune responses.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Innate defense regulator peptide synergizes with CpG ODN for enhanced innate intestinal immune responses in neonate piglets

Yang¹,

Mao²,

Zhang³

et al. 2012

International Immunopharmacology

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Host defense peptides: An alternative as antiinfective and immunomodulatory therapeutics

2012

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Host defense peptides are conserved components of innate immune response present among all classes of life. These peptides are potent, broad spectrum antimicrobial agents with potential as novel therapeutic compounds. Also, the ability of host defense peptides to modulate immunity is an emerging therapeutic concept since its selective modulation is a novel antiinfective strategy. Their mechanisms of action and the fundamental differences between pathogens and host cells surfaces mostly lead to a not widely extended microbial resistance and to a lower toxicity toward host cells. Biological libraries and rational design are novel tools for developing such molecules with promising applications as therapeutic drugs.

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Synthetic innate defence regulator peptide enhances in vivo immunostimulatory effects of CpG-ODN in newborn piglets

Cited by 21 publications

References 44 publications

In Vitro and In Vivo Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method

In Vitro and In Vivo Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method

Innate defense regulator peptide synergizes with CpG ODN for enhanced innate intestinal immune responses in neonate piglets

Host defense peptides: An alternative as antiinfective and immunomodulatory therapeutics

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