title: Pooled-sera hSBA titres predict individual seroprotection in infants and toddlers vaccinated with 4CMenB.
abstract: The Serum Bactericidal Antibody assay with human complement (hSBA) using individual immune sera is a surrogate of protection for meningococcal vaccines. Strain coverage of 4CMenB, a licensed vaccine against serogroup B meningococcal (MenB) disease, has been extensively assessed in hSBA using pooled sera, directly or through the Meningococcal Antigen Typing System (MATS). The extent to which pooled-sera hSBA titres reflect individual protection is not yet fully understood. We analysed more than 17000 individual hSBA titres from infants and toddlers vaccinated with 4CMenB, pooled-serum hSBA titres from subsets therein and MATS data from a 40 strain panel representative of invasive MenB disease in England and Wales. Individual hSBA titres segregated in two normal distributions, respectively from responding and non-responding subjects (fit_model-data: r=0.996, p-values <0.05). No individual subject showed abnormally high titres compared to the distributions. Also, when sera from the same subjects were tested individually and in pool, pooled-sera titre and average of individual titres from the same group were substantially indistinguishable (r=0.97, p-value <<0.001). We identified a robust mathematical relationship between the mean of individual hSBA titres and the proportion of subjects achieving a protective titre (seroprotection rate, r=0.95, p-value <<0.001). Using this relation, the seroprotection rate in 15 groups of vaccinees tested against 11 diverse meningococcal isolates was accurately predicted by the hSBA titre of the respective pooled sera (average prediction error 9%). Finally, strains defined covered by MATS had on average 77% predicted seroprotection rate (interquartile range, IQR: 66-100%) and 39% for non-covered strains (IQR: 19-46%). We conclude that seroprotection rates in infants and toddlers vaccinated with 4CMenB can be accurately predicted by pooled-serum hSBA, and that strain coverage defined by MATS is associated with high seroprotection rates.
  
  
  
  The Serum Bactericidal Antibody assay (SBA) from individual sera is a surrogate of protection for meningococcal vaccines. We show that SBA performed on pooled sera predicts individual protection.
authors.affiliation: GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Budroni
authors.affiliation: GSK Vaccines, Emil-von-Behring-Straße 76, 35041 Marburg, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Kleinschmidt
authors.affiliation: PRA Health Sciences (on assignment to GSK Vaccines), 520 Virginia Drive, Fort Washington, PA 19034, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Boucher
authors.affiliation: GSK Vaccines, Via Fiorentina 1, 53100 Siena, Italy. Electronic address: duccio.x.medini@gsk.com.
authors.forename: Duccio
authors.initials: D
authors.lastname: Medini
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D004739:England; D006801:Humans; D007223:Infant; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000627:therapeutic use*; D008962:Models, Theoretical; D038541:Neisseria meningitidis, Serogroup B; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D058248:Serum Bactericidal Antibody Assay; D014852:Wales
chemical_list: C570015:4CMenB vaccine; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines
keywords: 4CMenB Vaccine; Meningococcal disease; Pooled sera; Serum Bactericidal Antibody Assay with human complement hSBA; Surrogate of protection