Immunogenicity and safety of the candidate RTS,S/AS01 vaccine in young Nigerian children: A randomized, double-blind, lot-to-lot consistency trial

Umeh, Rich and Oguche, Stephen and Oguonu, T. and Pitmang, Simon and Shu, Elvis and Onyia, Jude T. and Daniyam, Comfort A. and Shwe, David and Ahmad, Abdullahi and Jongert, Erik and Catteau, Grégory and Lievens, Marc and Opokua, Ofori-Anyinam and Leach, Amanda (2014) Immunogenicity and safety of the candidate RTS,S/AS01 vaccine in young Nigerian children: A randomized, double-blind, lot-to-lot consistency trial. Vaccine, 32 (1). pp. 6556-6562.

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Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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 noninferior to that of a lot formulated from a pilot-scale antigen bulk batch.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: Uchenna Eneogwe
Date Deposited: 31 May 2025 07:32
Last Modified: 31 May 2025 07:32
URI: http://eprints.gouni.edu.ng/id/eprint/4711

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