Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection

被引：184

作者：

Lyke, Kirsten E. ^{[1
,2
]}

Ishizuka, Andrew S. ^{[3
]}

Berry, Andrea A. ^{[1
,2
]}

Chakravarty, Sumana ^{[4
]}

DeZure, Adam ^{[3
]}

Enama, Mary E. ^{[3
]}

James, Eric R. ^{[4
]}

Billingsley, Peter F. ^{[4
]}

Gunasekera, Anusha ^{[4
]}

Manoj, Anita ^{[4
]}

Li, Minglin ^{[4
,5
]}

Ruben, Adam J. ^{[4
]}

Li, Tao ^{[4
]}

Eappen, Abraham G. ^{[4
]}

Stafford, Richard E. ^{[4
,5
]}

Natasha, K. C. ^{[4
,5
]}

Murshedkar, Tooba ^{[4
]}

Mendoza, Floreliz H. ^{[3
]}

Gordon, Ingelise J. ^{[3
]}

Zephir, Kathryn L. ^{[3
]}

Holman, LaSonji A. ^{[3
]}

Plummer, Sarah H. ^{[3
]}

Hendel, Cynthia S. ^{[3
]}

Novik, Laura ^{[3
]}

Costner, Pamela J. M. ^{[3
]}

Saunders, Jamie G. ^{[3
]}

Berkowitz, Nina M. ^{[3
]}

Flynn, Barbara J. ^{[3
]}

Nason, Martha C. ^{[6
]}

Garver, Lindsay S. ^{[7
]}

Laurens, Matthew B. ^{[1
,2
]}

Plowe, Christopher V. ^{[1
,2
]}

Richie, Thomas L. ^{[4
]}

Graham, Barney S. ^{[3
]}

Roederer, Mario ^{[3
]}

Sim, B. Kim Lee ^{[4
,5
]}

Ledgerwood, Julie E. ^{[3
]}

Hoffman, Stephen L. ^{[4
]}

Seder, Robert A. ^{[3
]}

机构：

[1] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA

[2] Univ Maryland, Sch Med, Inst Global Hlth, Div Malaria Res, Baltimore, MD 21201 USA

[3] NIAID, VRC, NIH, Bethesda, MD 20892 USA

[4] Sanaria Inc, Rockville, MD 20850 USA

[5] Prot Potential LLC, Rockville, MD 20850 USA

[6] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA

[7] Walter Reed Army Inst Res, Entomol Branch, Silver Spring, MD 20910 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2017年 / 114卷 / 10期

基金：

美国国家卫生研究院;

关键词：

plasmodium; live-attenuated vaccine; T-cell immunology; malaria; sporozoite; FALCIPARUM-MALARIA; PLASMODIUM; IMMUNIZATION; RESPONSES; EFFICACY; ANTIGEN; MOSQUITOS;

D O I：

10.1073/pnas.1615324114

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 x 10(5) PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls (P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ- specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.

引用

页码：2711 / 2716

页数：6

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