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

Kamal El Bissati, Aziz A Chentoufi, Paulette A Krishack, Ying Zhou, Stuart Woods, Jitender P Dubey, Lo Vang, Joseph Lykins, Kate E Broderick, Ernest Mui, Yasuhiro Suzuki, Qila Sa, Stephanie Bi, Nestor Cardona, Shiv K Verma, Laura Frazeck, Catherine A Reardon, John Sidney, Jeff Alexander, Alessandro Sette & 4 others Tom Vedvick, Jeffrey A Guderian, Steven Reed, Craig W Roberts

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Abstract

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.

Original languageEnglish
JournalJCI Insight
Volume1
Issue number15
DOIs
Publication statusPublished - 22 Sep 2016

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T-Lymphocyte Epitopes
HLA-A Antigens
Toxoplasma
Emulsions
Cross-Priming
Transgenic Mice
Epitopes
Vaccines
Proteins
Toxoplasmosis
Helper-Inducer T-Lymphocytes
Endocytosis
Immunization
Parasites
Ligands
T-Lymphocytes
Lipids
Antigens
Peptides
DNA

Keywords

  • Toxoplasma gondii
  • HLA-A*1101
  • vaccine
  • DNA
  • multi-epitope protein

Cite this

El Bissati, Kamal ; Chentoufi, Aziz A ; Krishack, Paulette A ; Zhou, Ying ; Woods, Stuart ; Dubey, Jitender P ; Vang, Lo ; Lykins, Joseph ; Broderick, Kate E ; Mui, Ernest ; Suzuki, Yasuhiro ; Sa, Qila ; Bi, Stephanie ; Cardona, Nestor ; Verma, Shiv K ; Frazeck, Laura ; Reardon, Catherine A ; Sidney, John ; Alexander, Jeff ; Sette, Alessandro ; Vedvick, Tom ; Guderian, Jeffrey A ; Reed, Steven ; Roberts, Craig W. / Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii. In: JCI Insight. 2016 ; Vol. 1, No. 15.
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abstract = "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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El Bissati, K, Chentoufi, AA, Krishack, PA, Zhou, Y, Woods, S, Dubey, JP, Vang, L, Lykins, J, Broderick, KE, Mui, E, Suzuki, Y, Sa, Q, Bi, S, Cardona, N, Verma, SK, Frazeck, L, Reardon, CA, Sidney, J, Alexander, J, Sette, A, Vedvick, T, Guderian, JA, Reed, S & Roberts, CW 2016, 'Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii', JCI Insight, vol. 1, no. 15. https://doi.org/10.1172/jci.insight.85955

Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii. / El Bissati, Kamal; Chentoufi, Aziz A; Krishack, Paulette A; Zhou, Ying; Woods, Stuart; Dubey, Jitender P; Vang, Lo; Lykins, Joseph; Broderick, Kate E; Mui, Ernest; Suzuki, Yasuhiro; Sa, Qila; Bi, Stephanie; Cardona, Nestor; Verma, Shiv K; Frazeck, Laura; Reardon, Catherine A; Sidney, John; Alexander, Jeff; Sette, Alessandro; Vedvick, Tom; Guderian, Jeffrey A; Reed, Steven; Roberts, Craig W.

In: JCI Insight, Vol. 1, No. 15, 22.09.2016.

Research output: Contribution to journalArticle

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T1 - Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

AU - El Bissati, Kamal

AU - Chentoufi, Aziz A

AU - Krishack, Paulette A

AU - Zhou, Ying

AU - Woods, Stuart

AU - Dubey, Jitender P

AU - Vang, Lo

AU - Lykins, Joseph

AU - Broderick, Kate E

AU - Mui, Ernest

AU - Suzuki, Yasuhiro

AU - Sa, Qila

AU - Bi, Stephanie

AU - Cardona, Nestor

AU - Verma, Shiv K

AU - Frazeck, Laura

AU - Reardon, Catherine A

AU - Sidney, John

AU - Alexander, Jeff

AU - Sette, Alessandro

AU - Vedvick, Tom

AU - Guderian, Jeffrey A

AU - Reed, Steven

AU - Roberts, Craig W

PY - 2016/9/22

Y1 - 2016/9/22

N2 - 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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KW - Toxoplasma gondii

KW - HLA-A1101

KW - vaccine

KW - DNA

KW - multi-epitope protein

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U2 - 10.1172/jci.insight.85955

DO - 10.1172/jci.insight.85955

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