title: Immunogenicity and safety of the candidate RTS,S/AS01 vaccine in young Nigerian children: a randomized, double-blind, lot-to-lot consistency trial.
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 non-inferior to that of a lot formulated from a pilot-scale antigen bulk batch.
authors: University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Enugu State, Nigeria.
authors: Rich
authors: R
authors: Umeh
authors: Jos University Teaching Hospital, University of Jos, Jos, Plateau State, Nigeria.
authors: Stephen
authors: S
authors: Oguche
authors: University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Enugu State, Nigeria.
authors: Tagbo
authors: T
authors: Oguonu
authors: Jos University Teaching Hospital, University of Jos, Jos, Plateau State, Nigeria.
authors: Simon
authors: S
authors: Pitmang
authors: University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Enugu State, Nigeria.
authors: Elvis
authors: E
authors: Shu
authors: University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Enugu State, Nigeria.
authors: Jude-Tony
authors: JT
authors: Onyia
authors: Jos University Teaching Hospital, University of Jos, Jos, Plateau State, Nigeria.
authors: Comfort A
authors: CA
authors: Daniyam
authors: Jos University Teaching Hospital, University of Jos, Jos, Plateau State, Nigeria.
authors: David
authors: D
authors: Shwe
authors: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors: Abdullahi
authors: A
authors: Ahmad
authors: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors: Erik
authors: E
authors: Jongert
authors: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors: Grégory
authors: G
authors: Catteau
authors: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors: Marc
authors: M
authors: Lievens
authors: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors: Opokua
authors: O
authors: Ofori-Anyinam
authors: GlaxoSmithKline Vaccines, Rixensart, Belgium. Electronic address: amanda.leach@gsk.com.
authors: Amanda
authors: A
authors: Leach
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood; D000917:Antibody Formation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology / Q000592:standards* / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D009549:Nigeria; D014614:Vaccines, Synthetic / Q000276:immunology / Q000592:standards* / Q000627:therapeutic use*
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; C577001:RTS,S-AS01 vaccine; D014614:Vaccines, Synthetic
keywords: Children; Consistency; Immunogenicity; Malaria; RTS,S/AS01; Safety