A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice

Ana Maria Valencia-Hernandez; Wei Yi Ng; Nazanin Ghazanfari; Sonia Ghilas; Maria N. de Menezes; Lauren E. Holz; Cheng Huang; Kieran English; Myo Naung; Peck Szee Tan; Kirsteen M. Tullett; Thiago M. Steiner; Matthias H. Enders; Lynette Beattie; Yu Cheng Chua; Claerwen M. Jones; Anton Cozijnsen; Vanessa Mollard; Yeping Cai; David G. Bowen; Anthony W. Purcell; Nicole L. La Gruta; Jose A. Villadangos; Tania de Koning-Ward; Alyssa E. Barry; Winfried Barchet; Ian A. Cockburn; Geoffrey I. McFadden; Stephanie Gras; Mireille H. Lahoud; Patrick Bertolino; Ralf B. Schittenhelm; Irina Caminschi; William R. Heath; Daniel Fernandez-Ruiz

doi:10.1016/j.chom.2020.04.010

A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver T_RM Cell-Mediated Immunity against Malaria in Mice

Ana Maria Valencia-Hernandez, Wei Yi Ng, Nazanin Ghazanfari, Sonia Ghilas, Maria N. de Menezes, Lauren E. Holz, Cheng Huang, Kieran English, Myo Naung, Peck Szee Tan, Kirsteen M. Tullett, Thiago M. Steiner, Matthias H. Enders, Lynette Beattie, Yu Cheng Chua, Claerwen M. Jones, Anton Cozijnsen, Vanessa Mollard, Yeping Cai, David G. BowenAnthony W. Purcell, Nicole L. La Gruta, Jose A. Villadangos, Tania de Koning-Ward, Alyssa E. Barry, Winfried Barchet, Ian A. Cockburn, Geoffrey I. McFadden, Stephanie Gras, Mireille H. Lahoud, Patrick Bertolino, Ralf B. Schittenhelm, Irina Caminschi, William R. Heath, Daniel Fernandez-Ruiz

Research output: Contribution to journal › Article › Research › peer-review

47 Citations (Scopus)

Abstract

Liver-resident memory CD8⁺ T (T_RM) cells remain in and constantly patrol the liver to elicit rapid immunity upon antigen encounter and can mediate efficient protection against liver-stage Plasmodium infection. This finding has prompted the development of immunization strategies where T cells are activated in the spleen and then trapped in the liver to form T_RM cells. Here, we identify PbRPL6_120-127, a H2-K^b-restricted epitope from the putative 60S ribosomal protein L6 (RPL6) of Plasmodium berghei ANKA, as an optimal antigen for endogenous liver T_RM cell generation and protection against malaria. A single dose vaccination targeting RPL6 provided effective and prolonged sterilizing immunity against high dose sporozoite challenges. Expressed throughout the parasite life cycle, across Plasmodium species, and highly conserved, RPL6 exhibits strong translation potential as a vaccine candidate. This is further advocated by the identification of a broadly conserved, immunogenic HLA-A^∗02:01-restricted epitope in P. falciparum RPL6.

Original language	English
Pages (from-to)	950-962
Number of pages	13
Journal	Cell Host & Microbe
Volume	27
Issue number	6
DOIs	https://doi.org/10.1016/j.chom.2020.04.010
Publication status	Published - 10 Jun 2020

Keywords

adaptive immmunity
antigen
CD8 T cell
dendritic cell targeting
epitope discovery
liver
malaria
T cell memory
tissue-resident memory T cell
vaccine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.chom.2020.04.010

Cite this

Valencia-Hernandez, A. M., Ng, W. Y., Ghazanfari, N., Ghilas, S., de Menezes, M. N., Holz, L. E., Huang, C., English, K., Naung, M., Tan, P. S., Tullett, K. M., Steiner, T. M., Enders, M. H., Beattie, L., Chua, Y. C., Jones, C. M., Cozijnsen, A., Mollard, V., Cai, Y., ... Fernandez-Ruiz, D. (2020). A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver T_RM Cell-Mediated Immunity against Malaria in Mice. Cell Host & Microbe, 27(6), 950-962. https://doi.org/10.1016/j.chom.2020.04.010

@article{dfb91dad4c1d48da86c348c9d99fb5dc,

title = "A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice",

abstract = "Liver-resident memory CD8+ T (TRM) cells remain in and constantly patrol the liver to elicit rapid immunity upon antigen encounter and can mediate efficient protection against liver-stage Plasmodium infection. This finding has prompted the development of immunization strategies where T cells are activated in the spleen and then trapped in the liver to form TRM cells. Here, we identify PbRPL6120-127, a H2-Kb-restricted epitope from the putative 60S ribosomal protein L6 (RPL6) of Plasmodium berghei ANKA, as an optimal antigen for endogenous liver TRM cell generation and protection against malaria. A single dose vaccination targeting RPL6 provided effective and prolonged sterilizing immunity against high dose sporozoite challenges. Expressed throughout the parasite life cycle, across Plasmodium species, and highly conserved, RPL6 exhibits strong translation potential as a vaccine candidate. This is further advocated by the identification of a broadly conserved, immunogenic HLA-A∗02:01-restricted epitope in P. falciparum RPL6.",

keywords = "adaptive immmunity, antigen, CD8 T cell, dendritic cell targeting, epitope discovery, liver, malaria, T cell memory, tissue-resident memory T cell, vaccine",

author = "Valencia-Hernandez, {Ana Maria} and Ng, {Wei Yi} and Nazanin Ghazanfari and Sonia Ghilas and {de Menezes}, {Maria N.} and Holz, {Lauren E.} and Cheng Huang and Kieran English and Myo Naung and Tan, {Peck Szee} and Tullett, {Kirsteen M.} and Steiner, {Thiago M.} and Enders, {Matthias H.} and Lynette Beattie and Chua, {Yu Cheng} and Jones, {Claerwen M.} and Anton Cozijnsen and Vanessa Mollard and Yeping Cai and Bowen, {David G.} and Purcell, {Anthony W.} and {La Gruta}, {Nicole L.} and Villadangos, {Jose A.} and {de Koning-Ward}, Tania and Barry, {Alyssa E.} and Winfried Barchet and Cockburn, {Ian A.} and McFadden, {Geoffrey I.} and Stephanie Gras and Lahoud, {Mireille H.} and Patrick Bertolino and Schittenhelm, {Ralf B.} and Irina Caminschi and Heath, {William R.} and Daniel Fernandez-Ruiz",

year = "2020",

month = jun,

day = "10",

doi = "10.1016/j.chom.2020.04.010",

language = "English",

volume = "27",

pages = "950--962",

journal = "Cell Host & Microbe",

issn = "1931-3128",

publisher = "Elsevier",

number = "6",

}

Valencia-Hernandez, AM, Ng, WY, Ghazanfari, N, Ghilas, S, de Menezes, MN, Holz, LE, Huang, C, English, K, Naung, M, Tan, PS , Tullett, KM, Steiner, TM, Enders, MH, Beattie, L, Chua, YC, Jones, CM, Cozijnsen, A, Mollard, V, Cai, Y, Bowen, DG, Purcell, AW , La Gruta, NL, Villadangos, JA, de Koning-Ward, T, Barry, AE, Barchet, W, Cockburn, IA, McFadden, GI, Gras, S , Lahoud, MH, Bertolino, P, Schittenhelm, RB , Caminschi, I, Heath, WR & Fernandez-Ruiz, D 2020, 'A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver T_RM Cell-Mediated Immunity against Malaria in Mice', Cell Host & Microbe, vol. 27, no. 6, pp. 950-962. https://doi.org/10.1016/j.chom.2020.04.010

TY - JOUR

T1 - A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice

AU - Valencia-Hernandez, Ana Maria

AU - Ng, Wei Yi

AU - Ghazanfari, Nazanin

AU - Ghilas, Sonia

AU - de Menezes, Maria N.

AU - Holz, Lauren E.

AU - Huang, Cheng

AU - English, Kieran

AU - Naung, Myo

AU - Tan, Peck Szee

AU - Tullett, Kirsteen M.

AU - Steiner, Thiago M.

AU - Enders, Matthias H.

AU - Beattie, Lynette

AU - Chua, Yu Cheng

AU - Jones, Claerwen M.

AU - Cozijnsen, Anton

AU - Mollard, Vanessa

AU - Cai, Yeping

AU - Bowen, David G.

AU - Purcell, Anthony W.

AU - La Gruta, Nicole L.

AU - Villadangos, Jose A.

AU - de Koning-Ward, Tania

AU - Barry, Alyssa E.

AU - Barchet, Winfried

AU - Cockburn, Ian A.

AU - McFadden, Geoffrey I.

AU - Gras, Stephanie

AU - Lahoud, Mireille H.

AU - Bertolino, Patrick

AU - Schittenhelm, Ralf B.

AU - Caminschi, Irina

AU - Heath, William R.

AU - Fernandez-Ruiz, Daniel

PY - 2020/6/10

Y1 - 2020/6/10

N2 - Liver-resident memory CD8+ T (TRM) cells remain in and constantly patrol the liver to elicit rapid immunity upon antigen encounter and can mediate efficient protection against liver-stage Plasmodium infection. This finding has prompted the development of immunization strategies where T cells are activated in the spleen and then trapped in the liver to form TRM cells. Here, we identify PbRPL6120-127, a H2-Kb-restricted epitope from the putative 60S ribosomal protein L6 (RPL6) of Plasmodium berghei ANKA, as an optimal antigen for endogenous liver TRM cell generation and protection against malaria. A single dose vaccination targeting RPL6 provided effective and prolonged sterilizing immunity against high dose sporozoite challenges. Expressed throughout the parasite life cycle, across Plasmodium species, and highly conserved, RPL6 exhibits strong translation potential as a vaccine candidate. This is further advocated by the identification of a broadly conserved, immunogenic HLA-A∗02:01-restricted epitope in P. falciparum RPL6.

AB - Liver-resident memory CD8+ T (TRM) cells remain in and constantly patrol the liver to elicit rapid immunity upon antigen encounter and can mediate efficient protection against liver-stage Plasmodium infection. This finding has prompted the development of immunization strategies where T cells are activated in the spleen and then trapped in the liver to form TRM cells. Here, we identify PbRPL6120-127, a H2-Kb-restricted epitope from the putative 60S ribosomal protein L6 (RPL6) of Plasmodium berghei ANKA, as an optimal antigen for endogenous liver TRM cell generation and protection against malaria. A single dose vaccination targeting RPL6 provided effective and prolonged sterilizing immunity against high dose sporozoite challenges. Expressed throughout the parasite life cycle, across Plasmodium species, and highly conserved, RPL6 exhibits strong translation potential as a vaccine candidate. This is further advocated by the identification of a broadly conserved, immunogenic HLA-A∗02:01-restricted epitope in P. falciparum RPL6.

KW - adaptive immmunity

KW - antigen

KW - CD8 T cell

KW - dendritic cell targeting

KW - epitope discovery

KW - liver

KW - malaria

KW - T cell memory

KW - tissue-resident memory T cell

KW - vaccine

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U2 - 10.1016/j.chom.2020.04.010

DO - 10.1016/j.chom.2020.04.010

M3 - Article

C2 - 32396839

AN - SCOPUS:85085278821

SN - 1931-3128

VL - 27

SP - 950

EP - 962

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 6

ER -

A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver T_RM Cell-Mediated Immunity against Malaria in Mice

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Drivers of effective T cell immunity

Protecting against malaria through liver-resident memory T cells

Understanding the complexity of antigen presentation

Monash Proteomics & Metabolomics Facility

Cite this

A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Projects

Drivers of effective T cell immunity

Protecting against malaria through liver-resident memory T cells

Understanding the complexity of antigen presentation

Equipment

Monash Proteomics & Metabolomics Facility

Cite this

A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver T_RM Cell-Mediated Immunity against Malaria in Mice