For regulatory approval, consistency in manufacturing of vaccine lots is expected to be demonstrated in confirmatory immunogenicity studies using two-sided equivalence trials. This randomized, double-blind study (NCT01323972) assessed consistency of three RTS,S/AS01 malaria vaccine batches formulated from commercial-scale purified antigen bulk lots in terms of anti-CS-responses induced. Healthy children aged 5-17 months were randomized (1:1:1:1) to receive RTS,S/AS01 at 0-1-2 months from one of three commercial-scale purified antigen bulk lots (1600 litres-fermentation scale; commercial-scale lots), or a comparator vaccine batch made from pilot-scale purified antigen bulk lot (20 litres-fermentation scale; pilot-scale lot). The co-primary objectives were to first demonstrate consistency of antibody responses against circumsporozoite (CS) protein at one month post-dose 3 for the three commercial-scale lots and second demonstrate non-inferiority of anti-CS antibody responses at one month post-dose 3 for the commercial-scale lots compared to the pilot-scale lot. Safety and reactogenicity were evaluated as secondary endpoints. One month post-dose-3, anti-CS antibody geometric mean titres (GMT) for the 3 commercial scale lots were 319.6 EU/ml (95% confidence interval (CI): 268.9-379.8), 241.4 EU/ml (207.6-280.7), and 302.3 EU/ml (259.4-352.3). Consistency for the RTS,S/AS01 commercial-scale lots was demonstrated as the two-sided 95% CI of the anti-CS antibody GMT ratio between each pair of lots was within the range of 0.5-2.0. GMT of the pooled commercial-scale lots (285.8 EU/ml (260.7-313.3)) was non-inferior to the pilot-scale lot (271.7 EU/ml (228.5-323.1)). Each RTS,S/AS01 lot had an acceptable tolerability profile, with infrequent reports of grade 3 solicited symptoms. No safety signals were identified and no serious adverse events were considered related to vaccination. RTS,S/AS01 lots formulated from commercial-scale purified antigen bulk batches induced a consistent anti-CS antibody response, and the anti-CS GMT of pooled commercial-scale lots was non-inferior to that of a lot formulated from a pilot-scale antigen bulk batch.
For regulatory approval , consistency in manufacturing of vaccine lots is expected to be demonstrated in confirmatory immunogenicity studies using two - sided equivalence trials . This randomized , double - blind study ( NCT01323972 ) assessed consistency of three RTS , S / AS01 malaria vaccine batches formulated from commercial - scale purified antigen bulk lots in terms of anti - CS - responses induced . Healthy children aged 5 - 17 months were randomized ( 1:1:1:1 ) to receive RTS , S / AS01 at 0 - 1 - 2 months from one of three commercial - scale purified antigen bulk lots ( 1600 litres - fermentation scale ; commercial - scale lots ) , or a comparator vaccine batch made from pilot - scale purified antigen bulk lot ( 20 litres - fermentation scale ; pilot - scale lot ) . The co - primary objectives were to first demonstrate consistency of antibody responses against circumsporozoite ( CS ) protein at one month post - dose 3 for the three commercial - scale lots and second demonstrate non - inferiority of anti - CS antibody responses at one month post - dose 3 for the commercial - scale lots compared to the pilot - scale lot . Safety and reactogenicity were evaluated as secondary endpoints . One month post - dose-3 , anti - CS antibody geometric mean titres ( GMT ) for the 3 commercial scale lots were 319.6 EU / ml ( 95 % confidence interval ( CI ) : 268.9 - 379.8 ) , 241.4 EU / ml ( 207.6 - 280.7 ) , and 302.3 EU / ml ( 259.4 - 352.3 ) . Consistency for the RTS , S / AS01 commercial - scale lots was demonstrated as the two - sided 95 % CI of the anti - CS antibody GMT ratio between each pair of lots was within the range of 0.5 - 2.0 . GMT of the pooled commercial - scale lots ( 285.8 EU / ml ( 260.7 - 313.3 ) ) was non - inferior to the pilot - scale lot ( 271.7 EU / ml ( 228.5 - 323.1 ) ) . Each RTS , S / AS01 lot had an acceptable tolerability profile , with infrequent reports of grade 3 solicited symptoms . No safety signals were identified and no serious adverse events were considered related to vaccination . RTS , S / AS01 lots formulated from commercial - scale purified antigen bulk batches induced a consistent anti - CS antibody response , and the anti - CS GMT of pooled commercial - scale lots was non - inferior to that of a lot formulated from a pilot - scale antigen bulk batch .
RTS S AS01 vaccine was developed to prevent which disease?
RTS S AS01 vaccine was developed to prevent which disease ?
malaria
malaria