Enhanced Th2 immunity after DNA prime–protein boost immunization with amyloid β (1–42) plus CpG oligodeoxynucleotides in aged rats

Subramanian, S.; Shree, A.N. Divya

doi:10.1016/j.neulet.2008.03.024

Cited by 16 publications

(10 citation statements)

References 41 publications

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“…The immune response following DNA immunizations in general is much lower compared to peptide immunizations and to enhance the antigen specific response boost immunizations are performed to enhance this response. Most commonly used is a protein/peptide or viral boost immunization to enhance the antibody response in DNA immunizations (Kim et al 2007, Subramanian & Divya Shree, 2008, Davtyan et al 2010). Our results show that it is also very efficient to augment a peptide immunization with a DNA boost.…”

Section: Discussionmentioning

confidence: 99%

“…To overcome a significantly lower antibody production following DNA immunizations, so called prime-boost regimens have been shown to be highly effective. (Kim et al 2007, Subramanian & Divya Shree, 2008, Davtyan et al 2010). This greater level of immunity is based on a heterologous prime boost protocol in which the antigen is applied via different routes and immunization sites.…”

Section: Introductionmentioning

confidence: 99%

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A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease

Lambracht-Washington

et al. 2013

Journal of Neuroimmunology

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Immunotherapy has the potential to provide a possible treatment therapy to prevent or delay Alzheimer Disease. In a clinical trial (AN1792) in which patients received this immunotherapy and received active Aβ1–42 peptide immunizations, treatment was stopped when 6% of patients showed signs of meningoencephalitis. Follow up on these patients led to the conclusion that the antibody response was beneficial in removing Aβ1–42 from brain but an accompanying inflammatory Th1 T cell response was harmful. As a safe alternative treatment targeting the same self protein, Aβ1–42, in brain, we and others are working on a DNA Aβ1–42 immunization protocol as the immune response to DNA immunizations differs in many aspects from immunizations with peptide antigens. Because the immune response to DNA vaccination has different kinetics and has a significantly lower antibody production, we evaluated two different prime boost regimens, Aβ1–42 DNA prime/ Aβ1–42 peptide boost and Aβ1–42 peptide prime/ Aβ1–42 DNA boost for their effectiveness in antibody production and possible side effects due to inflammatory T cell responses. While both boost regimes significantly enhanced the specific antibody production with comparable antibody concentrations, the absence of the Aβ1–42 T cell response (no proliferation and no cytokine production) is consistent with our previous findings using this DNA Aβ1–42 trimer immunization and greatly enhances the safety aspect for possible clinical use.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease

Lambracht-Washington

et al. 2013

Journal of Neuroimmunology

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“…On the basis of these data, we endeavored to test a DNA prime–protein boost regimen to enhance the efficacy of our AD epitope vaccine. To our knowledge, only one group has studied the DNA prime–peptide boost regimen using a whole-length Aβ 42 peptide, but could not enhance the immune response without adding an adjuvant (oligo-deoxynucleotides, CpG motif) 72. In contrast, in this study we show that a DNA prime–protein boost strategy induces a significantly higher anti-PADRE T-cell proliferation (Figure 5b) and a higher production of anti-Aβ antibodies compared with a DNA prime–DNA boost regimen (Figure 2b).…”

Section: Discussionmentioning

confidence: 99%

DNA prime–protein boost increased the titer, avidity and persistence of anti-Aβ antibodies in wild-type mice

et al. 2009

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Recently, we reported that a DNA vaccine, composed of three copies of a self B cell epitope of amyloid-b (Ab 42 ) and the foreign T-cell epitope, Pan DR epitope (PADRE), generated strong anti-Ab immune responses in wild-type and amyloid precursor protein transgenic animals. Although DNA vaccines have several advantages over peptideprotein vaccines, they induce lower immune responses in large animals and humans compared with those in mice. The focus of this study was to further enhance anti-Ab 11 immune responses by developing an improved DNA vaccination protocol of the prime-boost regimen, in which the priming step would use DNA and the boosting step would use recombinant protein. Accordingly, we generated DNA and recombinant protein-based epitope vaccines and showed that priming with DNA followed by boosting with a homologous recombinant protein vaccine significantly increases the anti-Ab antibody responses and do not change the immunoglobulin G1 (IgG1) profile of humoral immune responses. Furthermore, the antibodies generated by this prime-boost regimen were long-lasting and possessed a higher avidity for binding with an Ab 42 peptide. Thus, we showed that a heterologous prime-boost regimen could be an effective protocol for developing a potent Alzheimer's disease (AD) vaccine.

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“…CpG ODN as vaccine adjuvant has been shown to restore Ag-specific immune responses to OVA, diphtheria toxoid, hepatitis B, polysaccharide of S. pnuemoniae, amyloid b and tumor cells in aged mice and rats [81][82][83][84][85][86][87]. When 3-month-old (or young adult) and 18-monthold (or aged) mice were orally immunized with OVA plus CpG ODN as adjuvant, both groups of mice showed high and equivalent levels of OVA-specific systemic IgG and mucosal IgA Ab responses [88].…”

Section: Reviewmentioning

confidence: 99%

Mucosal immunosenescence: new developments and vaccines to control infectious diseases

Fujihashi

Kiyono

2009

Trends in Immunology

102

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Enhanced Th2 immunity after DNA prime–protein boost immunization with amyloid β (1–42) plus CpG oligodeoxynucleotides in aged rats

Cited by 16 publications

References 41 publications

A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease

A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease

DNA prime–protein boost increased the titer, avidity and persistence of anti-Aβ antibodies in wild-type mice

Mucosal immunosenescence: new developments and vaccines to control infectious diseases

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