BACKGROUND MenB-FHbp is a licensed meningococcal B vaccine targeting factor H-binding protein. Two phase 3 studies assessed the safety of the vaccine and its immunogenicity against diverse strains of group B meningococcus. METHODS We randomly assigned 3596 adolescents (10 to 18 years of age) to receive MenB-FHbp or hepatitis A virus vaccine and saline and assigned 3304 young adults (18 to 25 years of age) to receive MenB-FHbp or saline at baseline, 2 months, and 6 months. Immunogenicity was assessed in serum bactericidal assays that included human complement (hSBAs). We used 14 meningococcal B test strains that expressed vaccine-heterologous factor H-binding proteins representative of meningococcal B epidemiologic diversity; an hSBA titer of at least 1:4 is the accepted correlate of protection. The five primary end points were the proportion of participants who had an increase in their hSBA titer for each of 4 primary strains by a factor of 4 or more and the proportion of those who had an hSBA titer at least as high as the lower limit of quantitation (1:8 or 1:16) for all 4 strains combined after dose 3. We also assessed the hSBA responses to the primary strains after dose 2; hSBA responses to the 10 additional strains after doses 2 and 3 were assessed in a subgroup of participants only. Safety was assessed in participants who received at least one dose. RESULTS In the modified intention-to-treat population, the percentage of adolescents who had an increase in the hSBA titer by a factor of 4 or more against each primary strain ranged from 56.0 to 85.3% after dose 2 and from 78.8 to 90.2% after dose 3; the percentages of young adults ranged from 54.6 to 85.6% and 78.9 to 89.7%, after doses 2 and 3, respectively. Composite responses after doses 2 and 3 in adolescents were 53.7% and 82.7%, respectively, and those in young adults were 63.3% and 84.5%, respectively. Responses to the 4 primary strains were predictive of responses to the 10 additional strains. Most of those who received MenB-FHbp reported mild or moderate pain at the vaccination site. CONCLUSIONS MenB-FHbp elicited bactericidal responses against diverse meningococcal B strains after doses 2 and 3 and was associated with more reactions at the injection site than the hepatitis A virus vaccine and saline.

A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults / Ostergaard, L; Vesikari, T; Absalon, J; Beeslaar, J; Ward, Bj; Senders, S; Eiden, Jj; Jansen, Ku; Anderson, As; York, Lj; Jones, Tr; Harris, Sl; O'Neill, R; Radley, D1; Maansson, R1; Prégaldien, Jl1; Ginis, J1; Staerke, Nb1; Perez, Jl1; B1971009 and B1971016 Trial Investigators., Belle-Isle J; Elfassi, E; Fredette, P; Garfield, H; Girard, G; Lachance, P; Adamkova, E; Bartonova, E; Drazan, D; Dvorakova, J; Kosina, P; Kyjonkova, A; Ruzkova, R; Vitousova, E; Ahonen, A; Forsten, A; Karppa, T; Kokko, S; Lagerstrom-Tirri, Pm; Simila, Jk; Adelt, T; Behre, U; Schwarz, Tf; Castiglia, P; Esposito, S; Ferrera, G; Icardi, G; Brzostek, J; Hasiec, B; Konior, R; Pejcz, J; Szymanski, H; Witor, A; Faust, Sn; Finn, Ah; Heath, Pt; Pollard, Aj; Altamirano, Dd; Ashley CT, Jr; Bader, Gf; Bauer GH, Jr; Block SL, Jr; Brandon, Dm; Davis, Mg; Devalle, O; Egelhof, Rh; Essink, Bj; Fouch, Bb; Fox, Bp; Franklin, Er; Garscadden, Ag; Goswami, Up; Gregory, Dm; Helman, Ll; Houchin, Vg; Howard, Ce; Johnson, Ad; Johnston WH, Jr; Jordan, Ca; Kimmel, Ma; Klein, Tr; Krilov, Lr; Labarbera, Ap; Labuda JM, Ii; Latiolais, Tg; Lello, Lg; Lewis, Dh; Ley, Ja; London, Al; Martin, Ms; Mcguire, Mr; Mosteller, Vc; Naccarato, Tr; Nassim, Cg; Rey, Mr; Robbins, Ra; Rouse, Kg; Schear, Mj; Senders, Sd; Shepard, Js; Simpson, Mw; Slandzicki, Aj; Slechta, Sb; Tetrick, Ll; Varman, M; Wadsworth LT, Iii; Ware, Db; White, Jh; Wisman PP, Jr; Blouin, F; Dionne, M; Dzongowski, P; Heaton, Kj; Langley, Jm; O'Mahony, Mfj; Powell, Cn; Ward, Bj; Ostergaard, Lj; Haapaniemi, Tl; Paassilta, M; Volanen, Ik; Lepich, T; Smukalska, E; Tarczon, I; Tetiurka, Bm; Domingo, Jd; Morato, Av; Riera, Mt; Sanchez, Ca; Torrell, Jmr; Blumenau, J; Campbell, Ng; Cervantes, Ja; Douglas, Wg; Ensz, Dj; Ervin, Je; Fiel, Tc; Fragoso, Vg; Fried, Dl; Gleason, Gp; Green, Sl; Haggag, Az; Johnson, Ct; Khaira, Rs; Kirstein, Jl; Kravitz, Ae; Lederman, Sn; Marcadis, I; Miller, Ve; Moretti, Jm; Pragalos, Aa; Puopolo, Ad; Rubino, J; Seiden, Dj; Sharp, Sc; Sheldon, Ea; Shockey, Gr; Smith, Wb; Stringer, Jc; Strout, Cb; Studdard, He; Tresser, Njl.. - In: NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 377:24(2017), pp. 2349-2362. [10.1056/NEJMoa1614474]

A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults

Esposito S;
2017

Abstract

BACKGROUND MenB-FHbp is a licensed meningococcal B vaccine targeting factor H-binding protein. Two phase 3 studies assessed the safety of the vaccine and its immunogenicity against diverse strains of group B meningococcus. METHODS We randomly assigned 3596 adolescents (10 to 18 years of age) to receive MenB-FHbp or hepatitis A virus vaccine and saline and assigned 3304 young adults (18 to 25 years of age) to receive MenB-FHbp or saline at baseline, 2 months, and 6 months. Immunogenicity was assessed in serum bactericidal assays that included human complement (hSBAs). We used 14 meningococcal B test strains that expressed vaccine-heterologous factor H-binding proteins representative of meningococcal B epidemiologic diversity; an hSBA titer of at least 1:4 is the accepted correlate of protection. The five primary end points were the proportion of participants who had an increase in their hSBA titer for each of 4 primary strains by a factor of 4 or more and the proportion of those who had an hSBA titer at least as high as the lower limit of quantitation (1:8 or 1:16) for all 4 strains combined after dose 3. We also assessed the hSBA responses to the primary strains after dose 2; hSBA responses to the 10 additional strains after doses 2 and 3 were assessed in a subgroup of participants only. Safety was assessed in participants who received at least one dose. RESULTS In the modified intention-to-treat population, the percentage of adolescents who had an increase in the hSBA titer by a factor of 4 or more against each primary strain ranged from 56.0 to 85.3% after dose 2 and from 78.8 to 90.2% after dose 3; the percentages of young adults ranged from 54.6 to 85.6% and 78.9 to 89.7%, after doses 2 and 3, respectively. Composite responses after doses 2 and 3 in adolescents were 53.7% and 82.7%, respectively, and those in young adults were 63.3% and 84.5%, respectively. Responses to the 4 primary strains were predictive of responses to the 10 additional strains. Most of those who received MenB-FHbp reported mild or moderate pain at the vaccination site. CONCLUSIONS MenB-FHbp elicited bactericidal responses against diverse meningococcal B strains after doses 2 and 3 and was associated with more reactions at the injection site than the hepatitis A virus vaccine and saline.
A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults / Ostergaard, L; Vesikari, T; Absalon, J; Beeslaar, J; Ward, Bj; Senders, S; Eiden, Jj; Jansen, Ku; Anderson, As; York, Lj; Jones, Tr; Harris, Sl; O'Neill, R; Radley, D1; Maansson, R1; Prégaldien, Jl1; Ginis, J1; Staerke, Nb1; Perez, Jl1; B1971009 and B1971016 Trial Investigators., Belle-Isle J; Elfassi, E; Fredette, P; Garfield, H; Girard, G; Lachance, P; Adamkova, E; Bartonova, E; Drazan, D; Dvorakova, J; Kosina, P; Kyjonkova, A; Ruzkova, R; Vitousova, E; Ahonen, A; Forsten, A; Karppa, T; Kokko, S; Lagerstrom-Tirri, Pm; Simila, Jk; Adelt, T; Behre, U; Schwarz, Tf; Castiglia, P; Esposito, S; Ferrera, G; Icardi, G; Brzostek, J; Hasiec, B; Konior, R; Pejcz, J; Szymanski, H; Witor, A; Faust, Sn; Finn, Ah; Heath, Pt; Pollard, Aj; Altamirano, Dd; Ashley CT, Jr; Bader, Gf; Bauer GH, Jr; Block SL, Jr; Brandon, Dm; Davis, Mg; Devalle, O; Egelhof, Rh; Essink, Bj; Fouch, Bb; Fox, Bp; Franklin, Er; Garscadden, Ag; Goswami, Up; Gregory, Dm; Helman, Ll; Houchin, Vg; Howard, Ce; Johnson, Ad; Johnston WH, Jr; Jordan, Ca; Kimmel, Ma; Klein, Tr; Krilov, Lr; Labarbera, Ap; Labuda JM, Ii; Latiolais, Tg; Lello, Lg; Lewis, Dh; Ley, Ja; London, Al; Martin, Ms; Mcguire, Mr; Mosteller, Vc; Naccarato, Tr; Nassim, Cg; Rey, Mr; Robbins, Ra; Rouse, Kg; Schear, Mj; Senders, Sd; Shepard, Js; Simpson, Mw; Slandzicki, Aj; Slechta, Sb; Tetrick, Ll; Varman, M; Wadsworth LT, Iii; Ware, Db; White, Jh; Wisman PP, Jr; Blouin, F; Dionne, M; Dzongowski, P; Heaton, Kj; Langley, Jm; O'Mahony, Mfj; Powell, Cn; Ward, Bj; Ostergaard, Lj; Haapaniemi, Tl; Paassilta, M; Volanen, Ik; Lepich, T; Smukalska, E; Tarczon, I; Tetiurka, Bm; Domingo, Jd; Morato, Av; Riera, Mt; Sanchez, Ca; Torrell, Jmr; Blumenau, J; Campbell, Ng; Cervantes, Ja; Douglas, Wg; Ensz, Dj; Ervin, Je; Fiel, Tc; Fragoso, Vg; Fried, Dl; Gleason, Gp; Green, Sl; Haggag, Az; Johnson, Ct; Khaira, Rs; Kirstein, Jl; Kravitz, Ae; Lederman, Sn; Marcadis, I; Miller, Ve; Moretti, Jm; Pragalos, Aa; Puopolo, Ad; Rubino, J; Seiden, Dj; Sharp, Sc; Sheldon, Ea; Shockey, Gr; Smith, Wb; Stringer, Jc; Strout, Cb; Studdard, He; Tresser, Njl.. - In: NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 377:24(2017), pp. 2349-2362. [10.1056/NEJMoa1614474]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2864637
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