Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo

Kutzler, Michele A.; Kraynyak, K A; Nagle, Sarah; Parkinson, Rose; Zharikova, Darya; Chattergoon, Michael A.; Maguire, Henry; Muthumani, Kar; Ugen, Kenneth E.; Weiner, David B.

doi:10.1038/gt.2009.112

Cited by 54 publications

(60 citation statements)

References 53 publications

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“…Recent studies found that systemic immunization of animals with the CCR10 ligand CCL27 or CCL28 as an adjuvant increased titers of antigen-specific IgA antibodies in mucosal tissues such as intestines, suggesting that manipulating the CCR10/ligand axis could be useful in enhancing the vaccination efficacy against mucosal pathogens (28,29). It will be interesting to study how CCR10/ligands increase the mucosal IgA memory in this setting.…”

Section: Discussionmentioning

confidence: 99%

Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines

Yang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Chemokine receptor CCR10 is expressed by all intestinal IgA-producing plasma cells and is suggested to play an important role in positioning these cells in the lamina propria for proper IgA production to maintain intestinal homeostasis and protect against infection. However, interfering with CCR10 or its ligand did not impair intestinal IgA production under homeostatic conditions or during infection, and the in vivo function of CCR10 in the intestinal IgA response remains unknown. We found that an enhanced generation of IgA + cells in isolated lymphoid follicles of intestines offset defective intestinal migration of IgA + cells in CCR10-KO mice, resulting in the apparently normal IgA production under homeostatic conditions and in primary response to pathogen infection. However, the compensatorily generated IgA + cells in CCR10-KO mice carried fewer hypermutations in their Ig heavy chain alleles than those of WT mice, indicating that their IgA repertoires are qualitatively different, which might impact the intestinal homeostasis of microflora. In addition, CCR10-deficient long-lived IgA-producing plasma cells and IgA + memory B cells generated against the pathogen infection could not be maintained properly in intestines. Consequently, IgA memory responses to the pathogen reinfection were severely impaired in CCR10-KO mice. These findings elucidate critical roles of CCR10 in regulating the intestinal IgA response and memory maintenance and could help in design of vaccines against intestinal and possibly other mucosal pathogens.

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Section: Discussionmentioning

confidence: 99%

Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines

Yang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…In the present study, we selected 5 peptide epitopes -KSFKDILPK (SAG1 224-232 ), STFWPCLLR (SAG2C [13][14][15][16][17][18][19][20][21] ), AVVSLLRLLK (GRA5 89-98 ), SSAYVFSVK (SRS52A 250-258 ), and AMLTAFFLR (GRA6 [164][165][166][167][168][169][170][171][172] ) -that elicited IFN-γ from peripheral blood mononuclear leukocytes (PBMCs) from T. gondii seropositive HLA-A03 supertype humans. SAG1 is a surface protein expressed in tachyzoites and mediates adhesion of the parasite to the host cell prior to invasion (7,8).…”

Section: Introductionmentioning

confidence: 99%

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

et al. 2016

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We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion [GLA-SE]) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included 5 of our best down-selected CD8(+) T cell-eliciting epitopes, a universal CD4(+) helper T lymphocyte epitope (PADRE), and a secretory signal, all arranged for optimal MHC-I presentation. Their capacity to elicit immune and protective responses was studied using immunization of HLA-A*11:01 transgenic mice. These multi-epitope vaccines increased memory CD8(+) T cells that produced IFN-γ and protected mice against parasite burden when challenged with T. gondii. Endocytosis of emulsion-trapped protein and cross presentation of the antigens must account for the immunogenicity of our adjuvanted protein. Thus, our work creates an adjuvanted platform assembly of peptides resulting in cross presentation of CD8(+) T cell-eliciting epitopes in a vaccine that prevents toxoplasmosis

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“…The antitumor adjuvant effect of CCL21 was also demonstrated in a melanoma animal model (Yamano et al, 2006). In an influenza virus DNA vaccine study, we al-so observed that coinjection with chemokines, CCL27 and CCL28 induces long-lived viral neutralizing antibodies, leading to protection from morbidity and mortality associated from a lethal influenza virus challenge (Kutzler et al, 2009). Along with this, coinjection of HBsAg DNA vaccines with plasmid DNAs expressing CCL20 and a cytokine, Flt3 (fms-related tyrosine kinase 3) ligand induced Ag-specific immune responses in HBsAg transgenic mice by recovering DC functions (personal communication with Sidong Xiong), suggesting an important role of coinjection of certain chemokines and cytokines in overcoming Ag-specific immune tolerance.…”

Section: Cytokines and Chemokines As Adjuvantsmentioning

confidence: 89%

DNA Vaccines against Infectious Diseases and Cancer

Han¹,

Weiner²,

Sin³

2010

Biomolecules and Therapeutics

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-Progress in the development of DNA vaccines and their delivery strategies has been made since their initial concept as a next generation vaccine. Since DNA vaccine includes non-infectious DNA parts of pathogens, it can't cause disease yet it closely mimic the natural process of infection and immune responses. Despite their early promising results of controlling infectious diseases and cancer in small animal models, DNA vaccines failed to display a level of immunogenicity required for combating these diseases in humans, possibly due to their lower protein expression levels. However, increasing evidence has shown that DNA vaccines are clinically well-tolerated and safe. Furthermore, one notable advantage of DNA vaccines includes convenient utilities of plasmid DNAs coding for antigens. For instance, any emerging pathogens could be prevented easily and timely by allowing the simple exchange of antigen-encoding genes. In this review, newly developed DNA vaccine strategies, including electroporation, which has emerged as a potent method for DNA delivery, targeting infectious diseases and cancer will be discussed with a focus on any on-going DNA vaccine trials or progress made pre-clinically and in clinics.

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Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo

Cited by 54 publications

References 53 publications

Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines

Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

DNA Vaccines against Infectious Diseases and Cancer

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