Induction of antigen specific intrahepatic CD8+ T cell responses by a secreted heat shock protein based gp96-Ig-PfCA malaria vaccine.

Abstract

Introduction:

A highly efficacious and durable vaccine against malaria is an essential tool for global malaria eradication. One of the promising strategies to develop such a vaccine is to induce robust CD8+ T cell mediated immunity against malaria liver-stage parasites.

Methods:

Here we describe a novel malaria vaccine platform based on a secreted form of the heat shock protein, gp96-immunoglobulin, (gp96-Ig) to induce malaria antigen specific, memory CD8+ T cells. Gp96-Ig acts as an adjuvant to activate antigen presenting cells (APCs) and chaperone peptides/antigens to APCs for cross presentation to CD8+ T cells.

Results:

Our study shows that vaccination of mice and rhesus monkeys with HEK-293 cells transfected with gp96-Ig and two well-known Plasmodium falciparum CSP and AMA1 (PfCA) vaccine candidate antigens, induces liver-infiltrating, antigen specific, memory CD8+ T cell responses. The majority of the intrahepatic CSP and AMA1 specific CD8+ T cells expressed CD69 and CXCR3, the hallmark of tissue resident memory T cells (Trm). Also, we found intrahepatic, antigen-specific memory CD8+ T cells secreting IL-2, which is relevant for maintenance of effective memory responses in the liver.

Discussion:

Our novel gp96-Ig malaria vaccine strategy represents a unique approach to induce liver-homing, antigen-specific CD8+ T cells critical for Plasmodium liver-stage protection.

• Authors: Laura Padula, Eva Fisher, Wathsala Wijayalath, Noelle B Patterson, Jun Huang, Harini Ganeshan, Tanisha Robinson, François A Bates, Margaret A Hanson, Monica L Martin, Katelyn Rivas, Denisse Garcia, Kimberly A Edgel, Martha Sedegah, Eileen Villasante, Natasa Strbo
• Journal: Frontiers in immunology (Front Immunol) Vol. 14 Pg. 1130054 ( 2023) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 37056783 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2023 Padula, Fisher, Wijayalath, Patterson, Huang, Ganeshan, Robinson, Bates, Hanson, Martin, Rivas, Garcia, Edgel, Sedegah, Villasante and Strbo.

Chemical References

• Malaria Vaccines
• Heat-Shock Proteins
• Immunoglobulins
• Antigens, Protozoan

Topics

• Humans
• Malaria Vaccines
• Heat-Shock Proteins (metabolism)
• HEK293 Cells
• Malaria, Falciparum
• CD8-Positive T-Lymphocytes
• Immunoglobulins (metabolism)
• Antigens, Protozoan
• Malaria (prevention & control, metabolism)