Immune Responses to Whole-Organism Blood-Stage Malaria Vaccines

Malaria ◽  
2017 ◽  
pp. 197-210
Author(s):  
Amber I. Raja ◽  
Danielle I. Stanisic ◽  
Michael F. Good
Keyword(s):  
Immune Responses ◽  
Blood Stage ◽  
Malaria Vaccines ◽  
Blood Stage Malaria

scholarly journals Protection against malaria in mice is induced by blood stage–arresting histamine-releasing factor (HRF)–deficient parasites

2016 ◽  
Vol 213 (8) ◽  
pp. 1419-1428 ◽  
Author(s):  
Claudia Demarta-Gatsi ◽  
Leanna Smith ◽  
Sabine Thiberge ◽  
Roger Peronet ◽  
Pierre-Henri Commere ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plasmodium Berghei ◽  
Blood Cells ◽  
Housekeeping Genes ◽  
Blood Stage ◽  
Parasite Development ◽  
Rodent Models ◽  
Cell Responses ◽  
Blood Stage Malaria

Although most vaccines against blood stage malaria in development today use subunit preparations, live attenuated parasites confer significantly broader and more lasting protection. In recent years, Plasmodium genetically attenuated parasites (GAPs) have been generated in rodent models that cause self-resolving blood stage infections and induce strong protection. All such GAPs generated so far bear mutations in housekeeping genes important for parasite development in red blood cells. In this study, using a Plasmodium berghei model compatible with tracking anti–blood stage immune responses over time, we report a novel blood stage GAP that lacks a secreted factor related to histamine-releasing factor (HRF). Lack of HRF causes an IL-6 increase, which boosts T and B cell responses to resolve infection and leave a cross-stage, cross-species, and lasting immunity. Mutant-induced protection involves a combination of antiparasite IgG2c antibodies and FcγR+ CD11b+ cell phagocytes, especially neutrophils, which are sufficient to confer protection. This immune-boosting GAP highlights an important role of opsonized parasite-mediated phagocytosis, which may be central to protection induced by all self-resolving blood stage GAP infections.

scholarly journals ChAd63-MVA–vectored Blood-stage Malaria Vaccines Targeting MSP1 and AMA1: Assessment of Efficacy Against Mosquito Bite Challenge in Humans

2012 ◽  
Vol 20 (12) ◽  
pp. 2355-2368 ◽  
Author(s):  
Susanne H Sheehy ◽  
Christopher JA Duncan ◽  
Sean C Elias ◽  
Prateek Choudhary ◽  
Sumi Biswas ◽  
...  
Keyword(s):  
Blood Stage ◽  
Mosquito Bite ◽  
Malaria Vaccines ◽  
Blood Stage Malaria

scholarly journals Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2

2020 ◽  
Vol 6 (9) ◽  
pp. eaay9269
Author(s):  
Yong Fu ◽  
Yan Ding ◽  
Qinghui Wang ◽  
Feng Zhu ◽  
Yulong Tan ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Underlying Mechanism ◽  
Innate Immune ◽  
Blood Stage ◽  
Innate Immune Responses ◽  
Malaria Parasites ◽  
Monocyte Chemoattractant Protein 1 ◽  
Blood Stage Malaria

Malaria parasites suppress host immune responses to facilitate their survival, but the underlying mechanism remains elusive. Here, we found that blood-stage malaria parasites predominantly induced CD4+Foxp3+CD25+ regulatory T cells to release soluble fibrinogen-like protein 2 (sFGL2), which substantially enhanced the infection. This was attributed to the capacity of sFGL2 to inhibit macrophages from releasing monocyte chemoattractant protein-1 (MCP-1) and to sequentially reduce the recruitment of natural killer/natural killer T cells to the spleen and the production of interferon-γ. sFGL2 inhibited c-Jun N-terminal kinase phosphorylation in the Toll-like receptor 2 signaling pathway of macrophages dependent on FcγRIIB receptor to release MCP-1. Notably, sFGL2 were markedly elevated in the sera of patients with malaria, and recombinant FGL2 substantially suppressed Plasmodium falciparum from inducing macrophages to release MCP-1. Therefore, we highlight a previously unrecognized immune suppression strategy of malaria parasites and uncover the fundamental mechanism of sFGL2 to suppress host innate immune responses.

Blood-stage malaria vaccines: post-genome strategies for the identification of novel vaccine candidates

2017 ◽  
Vol 16 (8) ◽  
pp. 769-779 ◽  
Author(s):  
Edward H. Ntege ◽  
Eizo Takashima ◽  
Masayuki Morita ◽  
Hikaru Nagaoka ◽  
Tomoko Ishino ◽  
...  
Keyword(s):  
Blood Stage ◽  
Vaccine Candidates ◽  
Malaria Vaccines ◽  
Blood Stage Malaria

scholarly journals A vaccine targeting the L9 epitope of the malaria circumsporozoite protein confers protection from blood-stage infection in a mouse challenge model

2021 ◽  
Author(s):  
Lucie Jelinkova ◽  
Yevel Flores-Garcia ◽  
Sarah Shapiro ◽  
Bryce T Roberts ◽  
Nikolai Petrovsky ◽  
...  
Keyword(s):  
High Titer ◽  
Antibody Responses ◽  
Circumsporozoite Protein ◽  
Blood Stage ◽  
Infection Model ◽  
Malaria Vaccines ◽  
Mouse Infection Model ◽  
Virus Like Particle ◽  
Blood Stage Infection ◽  
Blood Stage Malaria

Pre-erythrocytic malaria vaccines that induce high-titer, durable antibody responses can potentially provide protection from infection. Here, we engineered a virus-like particle (VLP)-based vaccine targeting a recently described vulnerable epitope at the N-terminus of the central repeat region of the Plasmodium falciparum circumsporozoite protein (CSP) that is recognized by the potently inhibitory monoclonal antibody L9 and show that immunization with L9 VLPs induces strong antibody responses that provide protection from blood-stage malaria in a mouse infection model.

Sign in / Sign up

Export Citation Format

Share Document