scholarly journals Structure and Function of HLA-A*02-Restricted Hantaan Virus Cytotoxic T-Cell Epitope That Mediates Effective Protective Responses in HLA-A2.1/Kb Transgenic Mice

2016 ◽  
Vol 7 ◽  
Author(s):  
Ying Ma ◽  
Linfeng Cheng ◽  
Bin Yuan ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
...  
1995 ◽  
Vol 7 (4) ◽  
pp. 597-605 ◽  
Author(s):  
Stephen Man ◽  
Michael H. Newberg ◽  
Victoria L. Crotzer ◽  
C. John Luckey ◽  
Noelle S. Williams ◽  
...  

2020 ◽  
Author(s):  
Ying Ma ◽  
Kang Tang ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
Linfeng Cheng ◽  
...  

Abstract Background: An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods: Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results: The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo.Conclusions: This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ying Ma ◽  
Kang Tang ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
Linfeng Cheng ◽  
...  

Abstract Background An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed. Methods Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test. Results The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo. Conclusions This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.


2020 ◽  
Author(s):  
Ying Ma ◽  
Kang Tang ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
Linfeng Cheng ◽  
...  

Abstract Background An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could inhibit HTNV replication in vivo.Conclusions This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.


2020 ◽  
Author(s):  
Ying Ma ◽  
Kang Tang ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
Linfeng Cheng ◽  
...  

Abstract Background: An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods: Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results: The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo.Conclusions: This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Michael Linnebacher ◽  
Anne Wienck ◽  
Inga Boeck ◽  
Ernst Klar

Microsatellite instability (MSI-H) induced by defects of the DNA mismatch repair system results in insertion or deletion of single nucleotides at short repetitive DNA sequences. About 15% of sporadic and approximately 90% of hereditary nonpolyposis colorectal cancers display MSI-H. When affecting coding regions, MSI-H results in frameshift mutations and expression of corresponding frameshift peptides (FSPs). Functional tumor promoting relevance has been demonstrated for a growing number of genes frequently hit by MSI-H. Contrary, immune reactions against FSPs are involved in the immune surveillance of MSI-H cancers. Here, we provide conclusive data that the (−1) frame ofU79260(FTO)encodes an HLA-A0201-restricted cytotoxic T cell epitope (FSP11; TLSPGWSAV). T cells specific for FSP11 efficiently recognized HLA-A0201(pos)tumor cells harboring the mutated reading frame. Considering the exceptionally high mutation rate ofU79260(FTO)in MSI-H colorectal carcinoma (81.8%), this recommends that FSP11 be a component of future vaccines.


Gene Therapy ◽  
2009 ◽  
Vol 16 (11) ◽  
pp. 1380-1382 ◽  
Author(s):  
E Breous ◽  
S Somanathan ◽  
J M Wilson

Sign in / Sign up

Export Citation Format

Share Document