Articles www.thelancet.com/infection Vol 11 June 2011 455 Lancet Infect Dis 2011; 11: 455–63 Published Online April 12, 2011 DOI:10.1016/S1473- 3099(11)70027-5 This online publication has been corrected. The corrected version first appeared at thelancet.com/ infection on June 20, 2011 See Comment page 421 Service des Maladies Infectieuses et Tropicales (Prof F Caron MD, J-P Leroy MD, V Delbos MD), Centre Régional de Pharmacovigilance (N Massy MD ), Département de Microbiologie (L Lemée PharmD), Unité de Biostatistiques (Prof J Bénichou MD), Hôpital Charles Nicolle , Université de Rouen (EA2656, INSERM U657), Rouen, France; Institut de Veille Sanitaire, Saint-Maurice, France (I Parent du Châtelet MD, D Lévy-Bruhl MD); Centre National de Référence des Méningocoques, Institut Pasteur, Paris, France (C Ruckly BSc, E Hong BSc, A-E Deghmane PhD, M-K Taha MD); Cellule Interrégionale d’Epidémiologie, Rouen, France (M Blanchard MSc, M Révillion MD); Agence Régionale de Santé, Rouen, France (J-P Leroy, N Bohic MD); Agence Française de Sécurité Sanitaire des Produits de Santé, Saint-Denis, France (I Morer MD); Comité Technique des Vaccinations, Paris, France (Prof D Floret MD); and Laboratoire de Bactériologie, Centre Hospitalier Général de Dieppe, Dieppe, France (G Berthelot PharmD) Correspondence to: Dr Isabelle Parent du Châtelet, 12 rue du val d’Osne, 94415 Saint-Maurice Cedex, France i.parent@invs.sante.fr From tailor-made to ready-to-wear meningococcal B vaccines: longitudinal study of a clonal meningococcal B outbreak François Caron, Isabelle Parent du Châtelet, Jean-Philippe Leroy, Corinne Ruckly, Myriam Blanchard, Nicole Bohic, Nathalie Massy, Isabelle Morer, Daniel Floret, Valérie Delbos, Eva Hong, Martin Révillion, Gilles Berthelot, Ludovic Lemée, Ala-Eddine Deghmane, Jacques Bénichou, Daniel Lévy-Bruhl, Muhamed-Kheir Taha Summary Background Outer-membrane-vesicle vaccines for meningococcal B outbreaks are complex and time consuming to develop. We studied the use of already available vaccine to control an outbreak caused by a genetically close strain. Methods From 2006 to 2009, all individuals younger than 20 years living in the region of Normandy, France, in which an outbreak caused by a B:14:P1.7,16 strain occurred, were eligible to receive MenBvac, a Norwegian vaccine designed 20 years earlier against a strain sharing the same serosubtype (B:15:P1.7,16). The immunogenicity (in a randomly selected cohort of 400 children aged 1–5 years), safety, and epidemiological effect of the vaccination were assessed. Findings 26 014 individuals were eligible to receive the vaccine. Shortage of vaccine production prompted start of the campaign in the highest incidence groups (1–5 years). 16 709 (64%) received a complete vaccination schedule of whom 13 589 (81%) received a 2+1 dose schedule (week 0, week 6, and month 8). At 6 weeks after the third dose, of 235 vaccinees for whom samples were available, 206 (88%) had a seroresponse, and 108 (56 %) of 193 had a seroresponse at 15 months. These results were similar to those described for tailor-made vaccines and their homologous strain. Only previously described adverse effects occurred. The incidence of B:14:P1.7,16 cases decreased significantly in the vaccine targeted population after the primary vaccination period (from 31·6 per 100 000 to 5·9 per 100 000; p=0·001). Interpretation The ready-to-wear approach is reliable if epidemic and vaccine strains are genetically close. Other meningococcal B clonal outbreaks might benefit from this strategy; and previously described outer-membrane-vesicle vaccines can be effective against various strains. Funding French Ministry of Health. Introduction Neisseria meningitidis is a leading cause of bacterial meningitis worldwide. 1 Invasive meningococcal infections also include severe meningococcaemia, an even more serious presentation of the disease. N meningitidis isolates are classified into 12 serogroups according to their capsular polysaccharide and into serotypes and serosubtypes according to their outer membrane proteins. Serogroup B isolates cause more than 50% of the invasive meningococcal infections in Europe. 2 Outbreaks occur mainly with the introduction of new meningococcal virulent clones in the population. 1 Compared with serogroup C, serogroup B outbreaks begin slowly and can persist longer, to up to more than a decade. 3–7 In the past 25 years, the annual incidence of invasive meningococcal infections in France has been low (0·7–1·6 cases per 100 000), with about 60% of the cases being of group B (0·4–0·8 per 100 000) of a large diversity of strains. 8 In 2003, the annual incidence of invasive meningococcal B infections reached 2 per 100 000 in Seine-Maritime (a district in Normandy, France) because of the expansion of a particular clone of serogroup B, serotype 14, serosubtype P1.7,16, and sequence type 32 (B:14:P1.7,16/ST-32) that had been present in this part of France since the 1990s. The most affected region of Seine-Maritime was the city of Dieppe and its immediate surroundings (Dieppe area), in which 60% of the cases of B:14:P1.7,16 occurred, although its population (92 770 inhabitants) represented only 7% of the total district population (1 243 800 inhabitants). 9 The control of invasive meningococcal infections of serogroup B is still a major public health challenge because of the absence of commercially available vaccines. Indeed, capsule-based vaccines are available only against serogroups A, C, Y, and W-135. They act universally against all the strains of each targeted serogroup. Attempts to process serogroup B capsular vaccines have failed because of poor immunogenicity and risk of autoimmunity. Promising new recombinant meningococcal B vaccines that offer large or universal coverage are expected in the near future. 10–12 Since the late 1980s, a few licensed tailor- made meningococcal B vaccines have been developed in response to a particular outbreak strain by use of outer membrane vesicles and all of them are reputed to be strain specific, especially in infants (cross-immune response has been described in children and adults). 13–16 The clinical