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Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area.

Polhemus ME, Remich SA, Ogutu BR, Waitumbi JN, Otieno L, Apollo S, Cummings JF, Kester KE, Ockenhouse CF, Stewart A, Ofori-Anyinam O, Ramboer I, Cahill CP, Lievens M, Dubois MC, Demoitie MA, Leach A, Cohen J, Ballou WR, Heppner DG - PLoS ONE (2009)

Bottom Line: Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3.Both candidate malaria vaccines were well tolerated over a 12 month surveillance period.A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.

View Article: PubMed Central - PubMed

Affiliation: US Army Medical Research Unit-Kenya, Nairobi, Kenya. mark.polhemus@us.army.mil

ABSTRACT

Background: This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.

Methodology: A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1ratio1ratio1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination.

Principal findings: Both candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5% (95% CI: -15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7% (95% CI: -11.6 to 58.2, p = 0.128).

Conclusions: Both candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.

Trial registration: Clinicaltrials.gov NCT00197054.

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Related in: MedlinePlus

Anti-CS GMTs over time (ATP cohort for immunogenicity).Note: bars represent 95% confidence intervals.
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pone-0006465-g003: Anti-CS GMTs over time (ATP cohort for immunogenicity).Note: bars represent 95% confidence intervals.

Mentions: Both malaria vaccines were immunogenic for anti-CS antibodies, with RTS,S/AS01B producing a significantly more robust response than RTS,S/AS02A (Figure 3). Pre-vaccination anti-CS GMTs were low and equivalent in the study groups. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A 1 month post Dose 2 (Day 60, p≤0.001), 1 month post Dose 3 (Day 90, p≤0.001), 4½ months post Dose 3 (Month 6½; p = 0.003) and 10 months post Dose 3 (Month 12; p = 0.002). Although anti-CS antibody GMTs decreased at 6 and 10 months post Dose 3, they remained higher in the RTS,S/AS01B compared to the RTS,S/AS02A group, and significantly greater in the candidate vaccine groups versus the rabies control group.


Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area.

Polhemus ME, Remich SA, Ogutu BR, Waitumbi JN, Otieno L, Apollo S, Cummings JF, Kester KE, Ockenhouse CF, Stewart A, Ofori-Anyinam O, Ramboer I, Cahill CP, Lievens M, Dubois MC, Demoitie MA, Leach A, Cohen J, Ballou WR, Heppner DG - PLoS ONE (2009)

Anti-CS GMTs over time (ATP cohort for immunogenicity).Note: bars represent 95% confidence intervals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2714466&req=5

pone-0006465-g003: Anti-CS GMTs over time (ATP cohort for immunogenicity).Note: bars represent 95% confidence intervals.
Mentions: Both malaria vaccines were immunogenic for anti-CS antibodies, with RTS,S/AS01B producing a significantly more robust response than RTS,S/AS02A (Figure 3). Pre-vaccination anti-CS GMTs were low and equivalent in the study groups. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A 1 month post Dose 2 (Day 60, p≤0.001), 1 month post Dose 3 (Day 90, p≤0.001), 4½ months post Dose 3 (Month 6½; p = 0.003) and 10 months post Dose 3 (Month 12; p = 0.002). Although anti-CS antibody GMTs decreased at 6 and 10 months post Dose 3, they remained higher in the RTS,S/AS01B compared to the RTS,S/AS02A group, and significantly greater in the candidate vaccine groups versus the rabies control group.

Bottom Line: Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3.Both candidate malaria vaccines were well tolerated over a 12 month surveillance period.A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.

View Article: PubMed Central - PubMed

Affiliation: US Army Medical Research Unit-Kenya, Nairobi, Kenya. mark.polhemus@us.army.mil

ABSTRACT

Background: This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.

Methodology: A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1ratio1ratio1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination.

Principal findings: Both candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5% (95% CI: -15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7% (95% CI: -11.6 to 58.2, p = 0.128).

Conclusions: Both candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A.

Trial registration: Clinicaltrials.gov NCT00197054.

Show MeSH
Related in: MedlinePlus