Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection

Tejram Sahu; Ella J. Gehrke; Yevel Flores-Garcia; Godfree Mlambo; Julia D. Romano; Isabelle Coppens

doi:10.1038/s41541-021-00360-1

Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection

Tejram Sahu, Ella J. Gehrke, Yevel Flores-Garcia, Godfree Mlambo, Julia D. Romano, Isabelle Coppens

Bloomberg School of Public Health

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

Abstract

Genetically attenuated sporozoite vaccines can elicit long-lasting protection against malaria but pose risks of breakthrough infection. Chemoprophylaxis vaccination (CVac) has proven to be the most effective vaccine strategy against malaria. Here, we demonstrate that a liver stage-specific autophagy mutant of Plasmodium berghei (ATG8 overexpressor), when used as a live vaccine under a CVac regimen, provides superior long-lasting protection, in both inbred and outbred mice, as compared to WT-CVac. Uniquely, the protection elicited by this mutant is predominantly dependent on a CD8⁺ T-cell response through an IFN-γ-independent mechanism and is associated with a stable population of antigen-experienced CD8⁺ T cells. Jointly, our findings support the exploitation of liver-stage mutants as vaccines under a CVac protocol. This vaccination strategy is also a powerful model to study the mechanisms of protective immunity and discover new protective antigens.

Original language	English (US)
Article number	98
Journal	npj Vaccines
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41541-021-00360-1
State	Published - Dec 2021

ASJC Scopus subject areas

Immunology
Pharmacology
Infectious Diseases
Pharmacology (medical)

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title = "Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection",

abstract = "Genetically attenuated sporozoite vaccines can elicit long-lasting protection against malaria but pose risks of breakthrough infection. Chemoprophylaxis vaccination (CVac) has proven to be the most effective vaccine strategy against malaria. Here, we demonstrate that a liver stage-specific autophagy mutant of Plasmodium berghei (ATG8 overexpressor), when used as a live vaccine under a CVac regimen, provides superior long-lasting protection, in both inbred and outbred mice, as compared to WT-CVac. Uniquely, the protection elicited by this mutant is predominantly dependent on a CD8+ T-cell response through an IFN-γ-independent mechanism and is associated with a stable population of antigen-experienced CD8+ T cells. Jointly, our findings support the exploitation of liver-stage mutants as vaccines under a CVac protocol. This vaccination strategy is also a powerful model to study the mechanisms of protective immunity and discover new protective antigens.",

author = "Tejram Sahu and Gehrke, {Ella J.} and Yevel Flores-Garcia and Godfree Mlambo and Romano, {Julia D.} and Isabelle Coppens",

note = "Funding Information: The authors are grateful to Fidel Zavala for helpful discussions throughout the course of this study, providing parasite strains and reagents, and critically reading the manuscript. The authors acknowledge the Johns Hopkins Malaria Research Institute (JHMRI) and the Bloomberg Philanthropies. We thank the Insectary and Parasitology Core Facilities of JHMRI, and the technical staff from the Johns Hopkins Microscopy Facility. We also acknowledge Photini Sinnis who provided mCherry-expressing Plasmodium berghei. This study was supported by a NIAID R56 AI080631 to I.C., a JHMRI pilot grant to I.C. and the Bloomberg Philanthropies. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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AU - Mlambo, Godfree

AU - Romano, Julia D.

AU - Coppens, Isabelle

N1 - Funding Information: The authors are grateful to Fidel Zavala for helpful discussions throughout the course of this study, providing parasite strains and reagents, and critically reading the manuscript. The authors acknowledge the Johns Hopkins Malaria Research Institute (JHMRI) and the Bloomberg Philanthropies. We thank the Insectary and Parasitology Core Facilities of JHMRI, and the technical staff from the Johns Hopkins Microscopy Facility. We also acknowledge Photini Sinnis who provided mCherry-expressing Plasmodium berghei. This study was supported by a NIAID R56 AI080631 to I.C., a JHMRI pilot grant to I.C. and the Bloomberg Philanthropies. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

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N2 - Genetically attenuated sporozoite vaccines can elicit long-lasting protection against malaria but pose risks of breakthrough infection. Chemoprophylaxis vaccination (CVac) has proven to be the most effective vaccine strategy against malaria. Here, we demonstrate that a liver stage-specific autophagy mutant of Plasmodium berghei (ATG8 overexpressor), when used as a live vaccine under a CVac regimen, provides superior long-lasting protection, in both inbred and outbred mice, as compared to WT-CVac. Uniquely, the protection elicited by this mutant is predominantly dependent on a CD8+ T-cell response through an IFN-γ-independent mechanism and is associated with a stable population of antigen-experienced CD8+ T cells. Jointly, our findings support the exploitation of liver-stage mutants as vaccines under a CVac protocol. This vaccination strategy is also a powerful model to study the mechanisms of protective immunity and discover new protective antigens.

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Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection

Abstract

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