Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes

Abstract 4CMenB is the first broad coverage vaccine for the prevention of invasive meningococcal disease caused by serogroup B strains. To gain a comprehensive picture of the antibody response induced upon 4CMenB vaccination and to obtain relevant translational information directly from human studie...

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Autores principales: M. Giuliani, E. Bartolini, B. Galli, L. Santini, P. Lo Surdo, F. Buricchi, M. Bruttini, B. Benucci, N. Pacchiani, L. Alleri, D. Donnarumma, W. Pansegrau, I. Peschiera, I. Ferlenghi, R. Cozzi, N. Norais, M. M. Giuliani, D. Maione, M. Pizza, R. Rappuoli, O. Finco, V. Masignani
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Publicado: Nature Portfolio 2018
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spelling oai:doaj.org-article:04f237cdf1e946fabada7b9dc0c872382021-12-02T15:07:57ZHuman protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes10.1038/s41598-018-22057-72045-2322https://doaj.org/article/04f237cdf1e946fabada7b9dc0c872382018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-22057-7https://doaj.org/toc/2045-2322Abstract 4CMenB is the first broad coverage vaccine for the prevention of invasive meningococcal disease caused by serogroup B strains. To gain a comprehensive picture of the antibody response induced upon 4CMenB vaccination and to obtain relevant translational information directly from human studies, we have isolated a panel of human monoclonal antibodies from adult vaccinees. Based on the Ig-gene sequence of the variable region, 37 antigen-specific monoclonal antibodies were identified and produced as recombinant Fab fragments, and a subset also produced as full length recombinant IgG1 and functionally characterized. We found that the monoclonal antibodies were cross-reactive against different antigen variants and recognized multiple epitopes on each of the antigens. Interestingly, synergy between antibodies targeting different epitopes enhanced the potency of the bactericidal response. This work represents the first extensive characterization of monoclonal antibodies generated in humans upon 4CMenB immunization and contributes to further unraveling the immunological and functional properties of the vaccine antigens. Moreover, understanding the mechanistic nature of protection induced by vaccination paves the way to more rational vaccine design and implementation.M. GiulianiE. BartoliniB. GalliL. SantiniP. Lo SurdoF. BuricchiM. BruttiniB. BenucciN. PacchianiL. AlleriD. DonnarummaW. PansegrauI. PeschieraI. FerlenghiR. CozziN. NoraisM. M. GiulianiD. MaioneM. PizzaR. RappuoliO. FincoV. MasignaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
M. Giuliani
E. Bartolini
B. Galli
L. Santini
P. Lo Surdo
F. Buricchi
M. Bruttini
B. Benucci
N. Pacchiani
L. Alleri
D. Donnarumma
W. Pansegrau
I. Peschiera
I. Ferlenghi
R. Cozzi
N. Norais
M. M. Giuliani
D. Maione
M. Pizza
R. Rappuoli
O. Finco
V. Masignani
Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes
description Abstract 4CMenB is the first broad coverage vaccine for the prevention of invasive meningococcal disease caused by serogroup B strains. To gain a comprehensive picture of the antibody response induced upon 4CMenB vaccination and to obtain relevant translational information directly from human studies, we have isolated a panel of human monoclonal antibodies from adult vaccinees. Based on the Ig-gene sequence of the variable region, 37 antigen-specific monoclonal antibodies were identified and produced as recombinant Fab fragments, and a subset also produced as full length recombinant IgG1 and functionally characterized. We found that the monoclonal antibodies were cross-reactive against different antigen variants and recognized multiple epitopes on each of the antigens. Interestingly, synergy between antibodies targeting different epitopes enhanced the potency of the bactericidal response. This work represents the first extensive characterization of monoclonal antibodies generated in humans upon 4CMenB immunization and contributes to further unraveling the immunological and functional properties of the vaccine antigens. Moreover, understanding the mechanistic nature of protection induced by vaccination paves the way to more rational vaccine design and implementation.
format article
author M. Giuliani
E. Bartolini
B. Galli
L. Santini
P. Lo Surdo
F. Buricchi
M. Bruttini
B. Benucci
N. Pacchiani
L. Alleri
D. Donnarumma
W. Pansegrau
I. Peschiera
I. Ferlenghi
R. Cozzi
N. Norais
M. M. Giuliani
D. Maione
M. Pizza
R. Rappuoli
O. Finco
V. Masignani
author_facet M. Giuliani
E. Bartolini
B. Galli
L. Santini
P. Lo Surdo
F. Buricchi
M. Bruttini
B. Benucci
N. Pacchiani
L. Alleri
D. Donnarumma
W. Pansegrau
I. Peschiera
I. Ferlenghi
R. Cozzi
N. Norais
M. M. Giuliani
D. Maione
M. Pizza
R. Rappuoli
O. Finco
V. Masignani
author_sort M. Giuliani
title Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes
title_short Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes
title_full Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes
title_fullStr Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes
title_full_unstemmed Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes
title_sort human protective response induced by meningococcus b vaccine is mediated by the synergy of multiple bactericidal epitopes
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/04f237cdf1e946fabada7b9dc0c87238
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