Intranasal administration of peptide antigens of HIV with mucosal adjuvant CpG ODN coentrapped in microparticles enhances the mucosal and systemic immune responses

Pun, Par Bahadur; Bhat, Ajaz A.; Mohan, Teena; Kulkarni, Smita; Paranjape, Ramesh; Rao, D. N.

doi:10.1016/j.intimp.2009.01.012

Cited by 24 publications

(12 citation statements)

References 44 publications

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“…There has been significant interest in using cytosine-phosphate-guanine (CpG)-containing oligodeoxynucleotides (ODNs) as an adjuvant for preventative therapeutic measures [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. CpG provides protection from a variety of pathogens, such as Klebsiella pneumoniae, Yersinia pestis, Listeria monocytogenes, Burkholderia pseudomallei , respiratory syncytial virus and human immunodeficiency virus, by enhancing non-specific immunity commonly associated with a strong polarized Th1-cell response, including increased production of IFN-γ and Th1-associated antibody isotypes [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Pre- and post-vaccination with CpG has been shown to protect and in some cases may contribute to the cessation of disease transmission [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…The activation of innate immunity by the administration of CpG has been shown to provide protection against an array of intracellular pathogens [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Against low aerosol challenge of B. mallei , BALB/c mice pre-treated with CpG had lower levels of bacterial burden in the lungs and increased survival compared to controls [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques

et al. 2013

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Burkholderia mallei, the etiologic agent of glanders, are Category B select agents with biothreat potential, and yet effective therapeutic treatments are lacking. In this study, we showed that CpG administration increased survival, demonstrating protection in the murine glanders model. Bacterial recovery from infected lungs, liver and spleen was significantly reduced in CpG-treated animals as compared with non-treated mice. Reciprocally, lungs of CpG-treated infected animals were infiltrated with higher levels of neutrophils and inflammatory monocytes, as compared to control animals. Employing the B. mallei bioluminescent strain CSM001 and the Neutrophil-Specific Fluorescent Imaging Agent, bacterial dissemination and neutrophil trafficking were monitored in real-time using multimodal in vivo whole body imaging techniques. CpG-treatment increased recruitment of neutrophils to the lungs and reduced bioluminescent bacteria, correlating with decreased bacterial burden and increased protection against acute murine glanders. Our results indicate that protection of CpG-treated animals was associated with recruitment of neutrophils prior to infection and demonstrated, for the first time, simultaneous real time in vivo imaging of neutrophils and bacteria. This study provides experimental evidence supporting the importance of incorporating optimized in vivo imaging methods to monitor disease progression and to evaluate the efficacy of therapeutic treatment during bacterial infections.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques

et al. 2013

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“…The effects of CpG ODN as adjuvant to enhance the immune response of coadministered antigens have been shown in many studies (Angel et al , ; Badiee et al , ; Bargieri et al , ; Cheng et al , ; Conforti et al , ; Kaushik et al , ; Mutwiri et al , ; Pun et al , ). For example, intranasal administration of peptide antigens of HIV with a Class B CpG ODN, CpG 1826 or CpG 2006, significantly enhanced peptide specific IgG and IgA peak titers and such responses were sustained for longer durations (Pun et al , ). The administration of recombinant outer membrane protein (rOMP28) of Brucella melitensis with CpG caused increased cell mediated immune response in terms of induced IgG2a, T‐cell proliferation and up‐regulation of type I cytokine expression (Kaushik et al , ).…”

Section: Discussionmentioning

confidence: 99%

A safety study of a B‐class CpG ODN in Sprague–Dawley rats

Liu

Shen

Liu

et al. 2011

J of Applied Toxicology

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Oligodeoxynucleotides containing CpG motifs (CpG ODNs) are potent immune activators and are being tested as anti-tumor, antimicrobial agents and as adjuvants in vaccines. Little has been reported, however, about the systematic and comprehensive safety evaluation on repeated CpG ODN administration. To investigate the safety profile of a newly developed CpG ODN, CpG 684, we conducted a 28-day repeated dose toxicity study in rats, at dose levels of 5, 20 and 150 µg CpG 684 per rat. No abnormalities in clinical observations, growth, urinalysis and bone marrow cell counts were found in CpG 684 treated rats. CpG 684 was proved biologically active, capable of up-regulating the expressions of CD40 and CD86 molecules. The monocyte numbers were increased at the dose levels of 20 and 150 µg per rat. The spleen weights were increased in female rats at the dose level of 150 µg per rat. Microscopically, 5, 20 and 150 µg per rat CpG 684 caused local inflammatory cell infiltration and hyperplasia of fibrous tissue at injection sites; the treatment of 5 and 150 µg per rat CpG 684 induced enhanced inflammatory reaction in inguinal lymphoid tissue, and the dose of 150 µg per rat induced cell hyperplasia in white pulp of spleen and white pulp expansion. CpG 684 at 150 µg per rat led to decreases in peripheral lymphocyte, serum globulin, glucose, alkaline phosphatase and K+ levels in female rats, and induced the decrease in serum albumin and total protein in rats of both sexes. The data from this study will provide an important reference for developing CpG 684 as an adjuvant for vaccines of human use.

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“…Therefore, we could speculate that CpG-oDN F3 was a strong inducer of functional maturation of chicken BM-DC. Many reports demonstrated that CpG-oDN was a potent adjuvant, which could promote the immune responses of an inactivated vaccine after mucosal immunization in mice (Pun et al, 2009). This may be due to the fact that CpG-oDN is a potent signal for growth, activation, and maturation of mouse DC.…”

Section: Discussionmentioning

confidence: 99%

The stimulatory effect of different CpG oligonucleotides on the maturation of chicken bone marrow-derived dendritic cells

et al. 2014

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CpG oligonucleotide (CpG-ODN) can exert an immunostimulatory effect on different types of immune cells such as dendritic cells (DC). The immunostimulatory activity of CpG-ODN is closely related to its nucleotide sequence and structural characteristics. In this study, we aimed at evaluating the stimulatory effects of different CpG-ODN on the maturation of chicken bone marrow-derived DC (BM-DC) in vitro. First, 4 CpG-ODN were designed. Then chicken bone marrow cells were extracted from tibia and femur and cultured in the RPMI 1640 medium with recombinant chicken granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After culture for 6 d, the cells were stimulated by different CpG-ODN or lipopolysaccharide for 24 h. Finally, the effects of different CpG-ODN on the maturation of chicken BM-DC were investigated by morphologic, phenotypic, and functional assays. The results showed that the cultured cells could display the typical DC morphology, and the CpG-ODN could efficiently stimulate the BM-DC to show the mature morphologic characteristics and upregulate the expression of cluster of differentiation (CD) 40 and CD86 molecules. In addition, after stimulation by CpG-ODN, the BM-DC could significantly induce T-cell proliferative response (P < 0.01). Among all the sequences, the stimulatory effect of CpG-ODN F3 with an addition of poly-guanosine strings at the 3' end was the best on the chicken BM-DC. In conclusion, this is the first report to demonstrate that different CpG-ODN have distinct stimulatory effects on the maturation of chicken BM-DC and CpG-ODN F3 with the best stimulatory effect can be a potent stimulant for the maturation of chicken BM-DC.

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Intranasal administration of peptide antigens of HIV with mucosal adjuvant CpG ODN coentrapped in microparticles enhances the mucosal and systemic immune responses

Cited by 24 publications

References 44 publications

Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques

Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques

A safety study of a B‐class CpG ODN in Sprague–Dawley rats

The stimulatory effect of different CpG oligonucleotides on the maturation of chicken bone marrow-derived dendritic cells

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