弱体化させたPfSPZマラリアワクチンの免疫機能への効果

//Background//---
 The morbidity and mortality induced by malaria have been significantly reduced (by a half) in this decade through the development of drug and anti-vector measures, but progress becomes sluggish(2), especially in the Africa. As the other infective disease like SARS, vaccination in a prophylactic manner is effective. The vaccine development is ongoing, but no human parasite vaccine has marketing authorization in the United States of America and Europe. The advanced malaria vaccine is following:
*RTS,S (also known by the trade name Mosquirix)
Targets a major surface protein (circum-sporozoite protein (CSP)) of P. falciparum sporozoites and confers partial protection against clinical malaria(3-5).
* Sanaria PfSPZ Vaccine
 Radiation-attenuated and non-replicative whole sporozoites, which can be significant protection against both homologous and heterologous (a different strain)(6-9).
 Typical clinical symptom in malaria infection is due to blood-stage parasites (Destruction of a red blood cell), so liver-stage kill is important.
 
//The main contents(1)//---
 Agnes Mwakingwe-Omari, Sara A. Healy, Jacquelyn Lane et al. optimized regimens in Sanaria PfSPZ Vaccine(1). In this way, this vaccine is aseptic, purified, cryopreserved, and is inoculated under prophylactic cover with the following two methods.
*Pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR))
*Chloroquine (CQ) (PfSPZ-CVac(CQ))
 They confirmed the live-stage kill for P. falciparum in vitro-model of human cell in PYR dose-dependent manner (1-100μM)(See Fig.1b).
PYR is superior to CQ for kill efficacy(See Fig.1a).
In (malaria antigen) challenge for the participants, vaccine efficacy of PfSPZ-CVac(PYR) is confirmed in a dose-dependent manner from 5.12×10^4 to 2×10^5.
In high dose regimen, 7 out of 8 (87.5%), 7 out of 9 (77.8%) individual is protected in 27days after challenge against homologous, heterologous CHMI, respectively(See Fig.2). Therefore, this PfSPZ-CVac will confer broadly protective sterilizing immunity against P. falciparum in the field.
Possible mechanism for the protection is associated with Vδ2 γδ T cell(See Fig.3) and antibody responses(See Fig.4). This γδ T cells suppress Plasmodium falciparum blood-stage infection through recognizing infected red blood cells (iRBC) and forming immune synapse, resulting lysis of iRBCs(12). We further need to investigate the comprehensive model of liver stage killing through vaccination, because, the liver stage killing may be clinically safer than the blood stage killing.
 
 //Previous achievement of PfSPZ Vaccine//---
 In Mari, 6 months protection in adults in the field study against P. falciparum(10)
 In the USA, equaled its vaccine efficacy in 6 months against CHMI with P. falciparum 7G8(6)
 
//Advantage of PfSPZ-CVac(PYR) in the Africa//---
 This vaccine is efficacious in the clinically silent liver stage. Therefore, prophylactic vaccination offers a wider safety margin. In Africa and other areas of high malaria transmission, pregnant women have already taken this vaccine after the first trimester. In addition, Millions of children in Sahel were inoculated in a monthly drug combination in the malaria progressive season(11). The excellent safety profile of this vaccine have been already confirmed(1).
 
//Contributions//---
S.A.H., S.L.H. and P.E.D. conceived and designed the study. A.M.-O., S.A.H., J.L., D.M.C., S.K., C.W., A.K., O.M.-S., A.I., L.K.D., H.D. and J.E.J. executed the clinical trials, with safety oversight by L.W.C.P. and T.L.R. T.M., A.M., A.G., B.K.L.S., P.F.B. and E.R.J. prepared the investigational product and coordinated regulatory affairs. M.N. analysed the clinical trial results. J.D., J.N., J.R., G.L., J.C.C.H., N.K., S.C., I.I., C.A., S.C.M., S.M., S.N.B. and I.Z. designed and performed laboratory studies. A.M.-O., S.L.H. and P.E.D. prepared the initial manuscript draft; all authors reviewed and edited the manuscript. A.M.-O. and S.A.H. supervised the trials and S.L.H. and P.E.D. supervised the study teams.
 
//Peer review information//---
 Nature thanks Stefan Kappe and Laurent Renia for their contribution to the peer review of this work. Peer reviewer reports are available.
 
(Reference)
(1)
Agnes Mwakingwe-Omari, Sara A. Healy, Jacquelyn Lane, David M. Cook, Sahand Kalhori, Charles Wyatt, Aarti Kolluri, Omely Marte-Salcedo, Alemush Imeru, Martha Nason, Lei K. Ding, Hope Decederfelt, Junhui Duan, Jillian Neal, Jacob Raiten, Grace Lee, Jen C. C. Hume, Jihyun E. Jeon, Ijeoma Ikpeama, Natasha KC, Sumana Chakravarty, Tooba Murshedkar, L. W. Preston Church, Anita Manoj, Anusha Gunasekera, Charles Anderson, Sean C. Murphy, Sandra March, Sangeeta N. Bhatia, Eric R. James, Peter F. Billingsley, B. Kim Lee Sim, Thomas L. Richie, Irfan Zaidi, Stephen L. Hoffman & Patrick E. Duffy
Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity
Nature (2021)
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Author information
Author notes
Agnes Mwakingwe-Omari
Present address: Center for Vaccine Research, GlaxoSmithKline, Rockville, MD, USA
These authors contributed equally: Agnes Mwakingwe-Omari, Sara A. Healy
These authors jointly supervised this work: Stephen L. Hoffman, Patrick E. Duffy
Affiliations
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Agnes Mwakingwe-Omari, Sara A. Healy, Jacquelyn Lane, David M. Cook, Sahand Kalhori, Charles Wyatt, Aarti Kolluri, Omely Marte-Salcedo, Alemush Imeru, Lei K. Ding, Junhui Duan, Jillian Neal, Jacob Raiten, Grace Lee, Jen C. C. Hume, Charles Anderson, Irfan Zaidi & Patrick E. Duffy
Biostatistical Research Branch, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA
Martha Nason
Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, USA
Hope Decederfelt & Jihyun E. Jeon
Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA
Ijeoma Ikpeama
Sanaria, Rockville, MD, USA
Natasha KC, Sumana Chakravarty, Tooba Murshedkar, L. W. Preston Church, Anita Manoj, Anusha Gunasekera, Eric R. James, Peter F. Billingsley, B. Kim Lee Sim, Thomas L. Richie & Stephen L. Hoffman
Protein Potential, Rockville, MD, USA
Natasha KC & B. Kim Lee Sim
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
Sean C. Murphy
Department of Microbiology, University of Washington, Seattle, WA, USA
Sean C. Murphy
Seattle Malaria Clinical Trials Center, Fred Hutch Cancer Research Center, Seattle, WA, USA
Sean C. Murphy
Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA, USA
Sean C. Murphy
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA
Sandra March & Sangeeta N. Bhatia
Koch Institute for Integrative Cancer Research, Cambridge, MA, USA
Sangeeta N. Bhatia
Broad Institute, Cambridge, MA, USA
Sangeeta N. Bhatia
Howard Hughes Medical Institute, Chevy Chase, MD, USA
Sangeeta N. Bhatia
Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Sangeeta N. Bhatia
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γδ T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis
Nature Immunology volume 22, pages347–357 (2021)
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Author information
Author notes
Sabrina Absalon
Present address: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA
These authors contributed equally: Caroline Junqueira, Rafael Polidoro.
Affiliations
Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA, USA
Caroline Junqueira, Rafael B. Polidoro, Zhitao Liang, Sumit Sen Santara, Ângela Crespo & Judy Lieberman
Department of Pediatrics, Harvard Medical School, Boston, MA, USA
Caroline Junqueira, Rafael B. Polidoro, Sabrina Absalon, Zhitao Liang, Sumit Sen Santara, Ângela Crespo, Jeffrey D. Dvorin & Judy Lieberman
Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil
Caroline Junqueira, Guilherme Castro & Ricardo T. Gazzinelli
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
Guilherme Castro & Ricardo T. Gazzinelli
Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA, USA
Sabrina Absalon & Jeffrey D. Dvorin
Centro de Pesquisa em Medicina Tropical de Rondônia, Porto Velho, RO, Brazil
Dhelio B. Pereira
Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
Ricardo T. Gazzinelli
Plataforma de Medicina Translacional, Fundação Oswaldo Cruz, Ribeirão Preto, SP, Brazil
Ricardo T. Gazzinelli