The effect of immunization schedule with the malaria vaccine candidate RTS,S/AS01E on protective efficacy and anti-circumsporozoite protein antibody avidity in African infants

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• 作者：Anthony Ajua (1)
  Bertrand Lell (1) (2)
  Selidji Todagbe Agnandji (2)
  Kwaku Poku Asante (3)
  Seth Owusu-Agyei (3) (4)
  Grace Mwangoka (5)
  Maxmilliam Mpina (5)
  Nahya Salim (5)
  Marcel Tanner (5) (6)
  Salim Abdulla (5)
  Johan Vekemans (7)
  Erik Jongert (7)
  Marc Lievens (7)
  Pierre Cambron (7)
  Chris F Ockenhouse (8)
  Peter G Kremsner (1) (2)
  Benjamin Mordm眉ller (1) (2)
  
  1. Eberhard Karls Universit盲t T眉bingen ; Institut f眉r Tropenmedizin ; Wilhelmstra脽e 27 ; 72074 ; T眉bingen ; Germany
  2. Centre de Recherches M茅dicales de Lambar茅n茅 (CERMEL) ; BP118 ; Lambar茅n茅 ; Gabon
  3. Kintampo Health Research Centre ; PO Box 200 ; Kintampo ; Ghana
  4. Faculty of Infectious and Tropical Diseases ; London School of Hygiene and Tropical Medicine ; Keppel Street ; London ; WC1E 7HT ; UK
  5. Bagamoyo Research and Training Centre of Ifakara Health Institute ; Bagamoyo ; 360 Kiko Avenue ; Mikocheni ; PO Box 78373 ; Dar es Salaam ; Tanzania
  6. Swiss Tropical and Public Health Institute ; Basel ; Switzerland
  7. GlaxoSmithKline Biologicals ; Rixensart ; Belgium
  8. PATH Malaria Vaccine Initiative ; 455 Massachusetts Avenue NW ; Suite 1000 ; Washington ; DC ; 20001 ; USA
  
• 关键词：Malaria ; RTS ; S ; Vaccine ; Plasmodium falciparum ; Antibody ; Avidity ; Correlate of protection
• 刊名：Malaria Journal
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：14
• 期：1
• 全文大小：1,043 KB
• 参考文献：1. Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BGNO, Kabwende AL, et al. A phase 3 trial of RTS, S/AS01 malaria vaccine in African infants. N Engl J Med. 2012;367:2284鈥?5. CrossRef
  2. Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, et al. First results of phase 3 trial of RTS, S/AS01 malaria vaccine in African children. N Engl J Med. 2011;365:1863鈥?5. CrossRef
  3. RTS,S Clinical Trials Partnership. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med. 2014;11:e1001685. CrossRef
  4. Olotu A, Lusingu J, Leach A, Lievens M, Vekemans J, Msham S, et al. Efficacy of RTS, S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5鈥?7 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis. 2011;11:102鈥?. CrossRef
  5. Asante KP, Abdulla S, Agnandji S, Lyimo J, Vekemans J, Soulanoudjingar S, et al. Safety and efficacy of the RTS, S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19聽month follow-up of a randomised, open-label, phase 2 trial. Lancet Infect Dis. 2011;11:741鈥?. CrossRef
  6. Aponte JJ, Aide P, Renom M, Mandomando I, Bassat Q, Sacarlal J, et al. Safety of the RTS, S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet. 2007;370:1543鈥?1. CrossRef
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  12. Agnandji ST, Asante KP, Lyimo J, Vekemans J, Soulanoudjingar SS, Owusu R, et al. Evaluation of the safety and immunogenicity of the RTS, S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization. J Infect Dis. 2010;202:1076鈥?7. CrossRef
  13. Clement F, Dewar V, Van Braeckel E, Desombere I, Dewerchin M, Swysen C, et al. Validation of an enzyme-linked immunosorbent assay for the quantification of human IgG directed against the repeat region of the circumsporozoite protein of the parasite / Plasmodium falciparum. Malar J. 2012;11:384. CrossRef
  14. Sabchareon A, Burnouf T, Ouattara D, Attanath P, Bouharoun-Tayoun H, Chantavanich P, et al. Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg. 1991;45:297鈥?08.
  15. Busse CE, Czogiel I, Braun P, Arndt PF, Wardemann H. Single-cell based high-throughput sequencing of full-length immunoglobulin heavy and light chain genes. Eur J Immunol. 2014;44:597鈥?03. CrossRef
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• 刊物主题：Parasitology; Infectious Diseases; Tropical Medicine;
• 出版者：BioMed Central
• ISSN：1475-2875

文摘

Background The malaria vaccine RTS,S induces antibodies against the Plasmodium falciparum circumsporozoite protein (CSP) and the concentration of Immunoglobulin G (IgG) against the repeat region of CSP following vaccination is associated with protection from P. falciparum malaria. So far, only the quantity of anti-CSP IgG has been measured and used to predict vaccination success, although quality (measured as avidity) of the antigen-antibody interaction shall be important since only a few sporozoites circulate for a short time after an infectious mosquito bite, likely requiring fast and strong binding. Methods Quantity and avidity of anti-CSP IgG in African infants who received RTS,S/AS01E in a 0-1-2-month or a 0-1-7-month schedule in a phase 2 clinical trial were measured by enzyme-linked immunosorbent assay. Antibody avidity was defined as the proportion of IgG able to bind in the presence of a chaotropic agent (avidity index). The effect of CSP-specific IgG concentration and avidity on protective efficacy was modelled using Cox proportional hazards. Results After the third dose, quantity and avidity were similar between the two vaccination schedules. IgG avidity after the last vaccine injection was not associated with protection, whereas the change in avidity following second and third RTS,S/AS01E injection was associated with a 54% risk reduction of getting malaria (hazard ratio: 0.46; 95% confidence interval (CI): 0.22-0.99) in those participants with a change in avidity above the median. The change in anti-CSP IgG concentration following second and third injection was associated with a 77% risk reduction of getting malaria (hazard ratio: 0.23, 95% CI: 0.11-0.51). Conclusions Change in IgG response between vaccine doses merits further evaluation as a surrogate marker for RTS,S efficacy. Trial registration ClinicalTrials.gov Identifier NCT00436007.