Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/ASO1E malaria vaccine efficacy

被引：104

作者：

Dobano, Carlota ^{[1
,2
]}

Sanz, Hector ^{[1
]}

Sorgho, Hermann ^{[3
]}

Dosoo, David ^{[4
]}

Mpina, Maximilian ^{[5
,6
,7
]}

Ubillos, Itziar ^{[1
]}

Aguilar, Ruth ^{[1
]}

Ford, Tom ^{[8
]}

Diez-Padrisa, Nuria ^{[1
]}

Aba Williams, Nana ^{[1
]}

Ayestaran, Aintzane ^{[1
]}

Traore, Ousmane ^{[3
]}

Nhabomba, Augusto J. ^{[2
]}

Jairoce, Chenjerai ^{[2
]}

Waitumbi, John ^{[9
]}

Agnandji, Selidji Todagbe ^{[10
,11
,12
]}

Kariuki, Simon ^{[13
]}

Abdulla, Salim ^{[5
]}

Aponte, John J. ^{[1
,2
]}

Mordmueller, Benjamin ^{[11
,12
]}

Asante, Kwaku Poku ^{[4
]}

Owusu-Agyei, Seth ^{[4
]}

Tinto, Halidou ^{[3
]}

Campo, Joseph J. ^{[1
,2
]}

Moncunill, Gemma ^{[1
,2
]}

Gyan, Ben ^{[4
,14
]}

Valim, Clarissa ^{[15
,16
,17
]}

Daubenberger, Claudia ^{[6
,7
]}

机构：

[1] Univ Barcelona, ISGlobal Hosp Clin, Rossello 153, E-08036 Barcelona, Catalonia, Spain

[2] CISM, Rua 12,Vila Manhica,CP 1929, Maputo, Mozambique

[3] Inst Rech Sci Sante, Unite Rech Clin Nanoro, BP 218, Nanoro, Burkina Faso

[4] Kintampo Hlth Res Ctr, POB 200 Kintampo, Brong Ahafo, Ghana

[5] Bagamoyo Res & Training Ctr, Ifakara Hlth Inst, POB 74, Bagamoyo, Tanzania

[6] Swiss Trop & Publ Hlth Inst, Socinstr 57, CH-4002 Basel, Switzerland

[7] Univ Basel, Peterspl 1, CH-4001 Basel, Switzerland

[8] Imperial Coll, IAVI Human Immunol Lab, 369 Fulham Rd, London SW10 9NH, England

[9] Kenya Govt Med Res Ctr, Walter Reed Army Inst Res, US Army Med Res Directorate Kenya, Box 54, Kisumu 40100, Kenya

[10] Ctr Rech Med Lambarene CERMEL, BP 242, Lambarene, Gabon

[11] Univ Tubingen, Inst Trop Med, Wilhelmstr 27, D-72074 Tubingen, Germany

[12] Univ Tubingen, German Ctr Infect Res, Wilhelmstr 27, D-72074 Tubingen, Germany

[13] Ctr Global Hlth, Kenya Med Res Inst, POB 54840, Siaya 00200, Nairobi, Kenya

[14] Univ Ghana, Noguchi Mem Inst Med Res, POB LG 581, Legon, Ghana

[15] Michigan State Univ, Dept Osteopath Med Specialties, 909 Fee Rd,Room B 309 West Fee Hall, E Lansing, MI 48824 USA

[16] Harvard TH Chen Sch Publ Hlth, Dept Immunol & Infect Dis, 675 Huntington Ave, Boston, MA 02115 USA

[17] Boston Univ, Dept Global Hlth, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院;

关键词：

PLASMODIUM-FALCIPARUM INFECTION; PHASE-3; TRIAL; PROTECTIVE EFFICACY; DOUBLE-BLIND; PROTEIN; CANDIDATE; CHILDREN; SAFETY; RTS; INFANTS;

D O I：

10.1038/s41467-019-10195-z

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：

RTS, S/ASO1E has been tested in a phase 3 malaria vaccine study with partial efficacy in African children and infants. In a cohort of 1028 subjects from one low (Bagomoyo) and two high (Nanoro, Kintampo) malaria transmission sites, we analysed IgG plasma/serum concentration and avidity to CSP (NANP-repeat and C-terminal domains) after a 3-dose vaccination against time to clinical malaria events during 12-months. Here we report that RTS, S/ AS01E induces substantial increases in IgG levels from pre-to post-vaccination (p < 0.001), higher in NANP than C-terminus (2855 vs 1297 proportional change between means), and higher concentrations and avidities in children than infants (p < 0.001). Baseline CSP IgG levels are elevated in malaria cases than controls (p < 0.001). Both, IgG magnitude to NANP (hazard ratio [95% confidence interval] 0.61 [0.48-0.76]) and avidity to C-terminus (0.07 [0.05-0.90]) post-vaccination are significantly associated with vaccine efficacy. IgG avidity to the C-terminus emerges as a significant contributor to RTS, S/ASO1E-mediated protection.

引用

页数：13

共 32 条

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