A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon

Bertrand Lell; Selidji Agnandji; Isabelle Von Glasenapp; Sonja Haertle; Sunny Oyakhiromen; Saadou Issifou; Johan Vekemans; Amanda Leach; Marc Lievens; Marie-Claude Dubois; Marie-Ange Demoitie; Terrell Carter; Tonya Villafana; Ripley Ballou; Joe Cohen; Peter Kremsner

doi:10.1371/journal.pone.0007611

A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon

Bertrand Lell, Selidji Agnandji, Isabelle Von Glasenapp, Sonja Haertle, Sunny Oyakhiromen, Saadou Issifou, Johan Vekemans, Amanda Leach, Marc Lievens, Marie-Claude Dubois, Marie-Ange Demoitie, Terrell Carter, Tonya Villafana, Ripley Ballou, Joe Cohen, Peter Kremsner

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Abstract

Background: The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion – based formulation (AS02) and a formulation based on liposomes (AS01).

Methods & Principal Findings: In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01E or RTS,S/AS02D, on a 0–1–2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02D/AS01E) of 0.88 (95% CI: 0.68–1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.

Conclusions: RTS,S/AS01E proved similarly as well tolerated and immunogenic as RTS,S/AS02D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.

Original language	English
Article number	e7611
Pages (from-to)	1-9
Number of pages	9
Journal	PLoS One
Volume	4
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0007611
Publication status	Published - 27 Oct 2009

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Lell, B., Agnandji, S., Von Glasenapp, I., Haertle, S., Oyakhiromen, S., Issifou, S., Vekemans, J., Leach, A., Lievens, M., Dubois, M-C., Demoitie, M-A., Carter, T., Villafana, T., Ballou, R., Cohen, J., & Kremsner, P. (2009). A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon. PLoS One, 4(10), 1-9. [e7611]. https://doi.org/10.1371/journal.pone.0007611

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title = "A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon",

abstract = "Background: The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion – based formulation (AS02) and a formulation based on liposomes (AS01).Methods & Principal Findings: In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01E or RTS,S/AS02D, on a 0–1–2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02D/AS01E) of 0.88 (95% CI: 0.68–1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.Conclusions: RTS,S/AS01E proved similarly as well tolerated and immunogenic as RTS,S/AS02D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.",

author = "Bertrand Lell and Selidji Agnandji and {Von Glasenapp}, Isabelle and Sonja Haertle and Sunny Oyakhiromen and Saadou Issifou and Johan Vekemans and Amanda Leach and Marc Lievens and Marie-Claude Dubois and Marie-Ange Demoitie and Terrell Carter and Tonya Villafana and Ripley Ballou and Joe Cohen and Peter Kremsner",

year = "2009",

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doi = "10.1371/journal.pone.0007611",

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Lell, B, Agnandji, S, Von Glasenapp, I, Haertle, S, Oyakhiromen, S, Issifou, S, Vekemans, J, Leach, A, Lievens, M, Dubois, M-C, Demoitie, M-A, Carter, T, Villafana, T, Ballou, R, Cohen, J & Kremsner, P 2009, 'A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon', PLoS One, vol. 4, no. 10, e7611, pp. 1-9. https://doi.org/10.1371/journal.pone.0007611

TY - JOUR

T1 - A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon

AU - Lell, Bertrand

AU - Agnandji, Selidji

AU - Von Glasenapp, Isabelle

AU - Haertle, Sonja

AU - Oyakhiromen, Sunny

AU - Issifou, Saadou

AU - Vekemans, Johan

AU - Leach, Amanda

AU - Lievens, Marc

AU - Dubois, Marie-Claude

AU - Demoitie, Marie-Ange

AU - Carter, Terrell

AU - Villafana, Tonya

AU - Ballou, Ripley

AU - Cohen, Joe

AU - Kremsner, Peter

PY - 2009/10/27

Y1 - 2009/10/27

N2 - Background: The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion – based formulation (AS02) and a formulation based on liposomes (AS01).Methods & Principal Findings: In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01E or RTS,S/AS02D, on a 0–1–2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02D/AS01E) of 0.88 (95% CI: 0.68–1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.Conclusions: RTS,S/AS01E proved similarly as well tolerated and immunogenic as RTS,S/AS02D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.

AB - Background: The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion – based formulation (AS02) and a formulation based on liposomes (AS01).Methods & Principal Findings: In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01E or RTS,S/AS02D, on a 0–1–2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02D/AS01E) of 0.88 (95% CI: 0.68–1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.Conclusions: RTS,S/AS01E proved similarly as well tolerated and immunogenic as RTS,S/AS02D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.

U2 - 10.1371/journal.pone.0007611

DO - 10.1371/journal.pone.0007611

M3 - Article

VL - 4

SP - 1

EP - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e7611

ER -

A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon

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