Recombinant Wolbachia surface protein (WSP)-induced T cell responses in Wuchereria bancrofti infections

ABSTRACT Vaccines for P. falciparum will need to contain both T- and B-cell epitopes. Conserved epitopes are the most desirable, but they are often poorly immunogenic. The major merozoite surface protein 1 (MSP-1) is currently a leading vaccine candidate antigen. In this study, six peptides from conserved or partly conserved regions of MSP-1 were evaluated for immunogenicity in B10 congenic mice. Following immunization with the peptides, murine T cells were tested for the ability to proliferate in vitro and antibody responses to MSP-1 were evaluated in vivo. The results showed that one highly conserved sequence (MSP-1#1, VTHESYQELVKKLEALEDAV; located at amino acid positions 20 to 39) and one partly conserved sequence (MSP-1#23, GLFHKEKMILNEEEITTKGA; located at positions 44 to 63) contained both T- and B-cell epitopes. Immunization of mice with these peptides resulted in T-cell proliferation and enhanced production of antibody to MSP-1 upon exposure to merozoites. MSP-1#1 stimulated T-cell responses in three of the six strains of mice evaluated, whereas MSP-1#23 was immunogenic in only one strain. Immunization with the other four peptides resulted in T-cell responses to the peptides, but none of the resulting peptide-specific T cells recognized native MSP-1. These results demonstrate that two sequences located in the N terminus of MSP-1 can induce T- and B-cell responses following immunization in a murine model. Clearly, these sequences merit further consideration for inclusion in a vaccine for malaria.

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Targeting a Plasmodium vivax merozoite surface protein 1 fragment to the DEC205+ dendritic cell population elicits strong antibody and T cell responses.

Frontiers in Immunology ◽

10.3389/conf.fimmu.2013.02.00557 ◽

2013 ◽

Vol 4 ◽

Author(s):

Amorim Kelly ◽

Yamamoto Marcio ◽

Boscardin Silvia

Keyword(s):

T Cell ◽

Dendritic Cell ◽

Plasmodium Vivax ◽

Cell Population ◽

Surface Protein ◽

T Cell Responses ◽

Merozoite Surface Protein ◽

Cell Responses ◽

Merozoite Surface Protein 1 ◽

Dendritic Cell Population

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Antibody and T Cell Responses in Reciprocal Prime-Boost Studies with Full-Length and Truncated Merozoite Surface Protein 1–42 Vaccines

PLoS ONE ◽

10.1371/journal.pone.0075939 ◽

2013 ◽

Vol 8 (9) ◽

pp. e75939

Author(s):

Kae Pusic ◽

Danielle Clements ◽

Sophie Kobuch ◽

George Hui

Keyword(s):

T Cell ◽

Surface Protein ◽

T Cell Responses ◽

Merozoite Surface Protein ◽

Full Length ◽

Cell Responses ◽

Merozoite Surface Protein 1

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CD4+ T-Cell- and Gamma Interferon-Dependent Protection against Murine Malaria by Immunization with Linear Synthetic Peptides from a Plasmodium yoelii17-Kilodalton Hepatocyte Erythrocyte Protein

Infection and Immunity ◽

10.1128/iai.67.11.5604-5614.1999 ◽

1999 ◽

Vol 67 (11) ◽

pp. 5604-5614 ◽

Cited By ~ 38

Author(s):

Yupin Charoenvit ◽

Victoria Fallarme Majam ◽

Giampietro Corradin ◽

John B. Sacci ◽

Ruobing Wang ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Synthetic Peptides ◽

Vaccine Development ◽

Surface Protein ◽

T Cell Responses ◽

Plasmodium Yoelii ◽

Gamma Interferon ◽

Cell Responses ◽

Ifn Γ

ABSTRACT Most work on protective immunity against the pre-erythrocytic stages of malaria has focused on induction of antibodies that prevent sporozoite invasion of hepatocytes, and CD8+ T-cell responses that eliminate infected hepatocytes. We recently reported that immunization of A/J mice with an 18-amino-acid synthetic linear peptide from Plasmodium yoelii sporozoite surface protein 2 (SSP2) in TiterMax adjuvant induces sterile protection that is dependent on CD4+ T cells and gamma interferon (IFN-γ). We now report that immunization of inbred A/J mice and outbred CD1 mice with each of two linear synthetic peptides from the 17-kDa P. yoelii hepatocyte erythrocyte protein (HEP17) in the same adjuvant also induces protection against sporozoite challenge that is dependent on CD4+ T cells and IFN-γ. The SSP2 peptide and the two HEP17 peptides are recognized by B cells as well as T cells, and the protection induced by these peptides appears to be directed against the infected hepatocytes. In contrast to the peptide-induced protection, immunization of eight different strains of mice with radiation-attenuated sporozoites induces protection that is absolutely dependent on CD8+ T cells. Data represented here demonstrate that CD4+ T-cell-dependent protection can be induced by immunization with linear synthetic peptides. These studies therefore provide the foundation for an approach to pre-erythrocytic-stage malaria vaccine development, based on the induction of protective CD4+ T-cell responses, which will complement efforts to induce protective antibody and CD8+T-cell responses.

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An optimized workflow for CRISPR-Cas9 deletion of surface and intracellular factors in primary human T lymphocytes

PLoS ONE ◽

10.1371/journal.pone.0247232 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0247232

Author(s):

Cristina Leoni ◽

Niccolò Bianchi ◽

Lucia Vincenzetti ◽

Silvia Monticelli

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Gene Editing ◽

Protein A ◽

Surface Protein ◽

T Cell Responses ◽

Cell Responses ◽

Human T Lymphocytes ◽

Human T Cell ◽

Non Coding Rna

The appropriate regulation of T lymphocyte functions is key to achieve protective immune responses, while at the same time limiting the risks of tissue damage and chronic inflammation. Deciphering the mechanisms underpinning T cell responses in humans may therefore be beneficial for a range of infectious and chronic diseases. Recently, the development of methods based on CRISPR-Cas9 gene-editing has greatly expanded the available tool-box for the mechanistic studies of primary human T cell responses. While the deletion of a surface protein has become a relatively straightforward task, as long as an antibody for detection is available, the identification and selection of cells lacking an intracellular protein, a non-coding RNA or a protein for which no antibody is available, remain more problematic. Here, we discuss the options currently available to scientists interested in performing gene-editing in primary human T lymphocytes and we describe the optimization of a workflow for the screening and analysis of lymphocytes following gene-editing with CRISPR-Cas9 based on T cell cloning and T7 endonuclease I cleavage assay.

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