Vaccine 31 (2013) 1113–1116
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Vaccine
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Could the multicomponent meningococcal serogroup B vaccine (4CMenB)
control Neisseria meningitidis capsular group X outbreaks in Africa?
Eva Hong
a
, Marzia Monica Giuliani
b
, Ala-Eddine Deghmane
a
, Maurizio Comanducci
b
,
Brunella Brunelli
b
, Peter Dull
b
, Mariagrazia Pizza
b
, Muhamed-Kheir Taha
a,∗
a
Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France
b
Novartis Vaccines and Diagnostics, Siena, Italy
a r t i c l e i n f o
Article history:
Received 17 August 2012
Received in revised form 6 December 2012
Accepted 8 December 2012
Available online 20 December 2012
Keywords:
Neisseria meningitidis
Vaccine
Serogroup X
Epidemics
African meningitis belt
a b s t r a c t
A new vaccine, 4CMenB, is composed of surface proteins of Neisseria meningitidis and is aimed to target
serogroup B (MenB) isolates. The vaccine components are present in meningococcal isolates of other
serogroups allowing potential use against meningococcal isolates belonging to non-B serogroups. Isolates
of serogroup X (MenX) have been emerged in countries of the African meningitis belt. 4CMenB may offer
a vaccine strategy against these isolates as there is no available capsule-based vaccine against MenX. We
used the Meningococcal Antigen Typing System (MATS) to determine presence, diversity and levels of
expression of 4CMenB antigens among 9 MenX isolates from several African countries in order to estimate
the potential coverage of MenX by the 4CMenB vaccine. We performed bactericidal assays against these
isolates, using pooled sera from 4CMenB-vaccinated infants, adolescents and adults. The African MenX
isolates belonged to the same genotype but showed variation in the vaccine antigens. MATS data and
bactericidal assays suggest coverage of the 9 African MenX isolates by 4CMenB but not of two unrelated
MenX isolates from France. 4CMenB vaccine can be considered for further investigation to control MenX
outbreaks in Africa.
© 2012 Elsevier Ltd. All rights reserved.
1. Introduction
Neisseria meningitidis (Nm), a human exclusive encapsulated
bacterium, may provoke invasive infections that are dominated by
septicaemia and meningitis. Sporadic cases occur in Europe and
North America. Major periodic epidemics have been occurring in
the African sub-Saharan countries from Ethiopia to Senegal [1].
The polysaccharide capsule determines the serogroup of isolates
and 12 meningococcal capsular groups are currently described.
Serogroups A, B, C, Y, W and X are responsible for the majority
of invasive meningococcal infections worldwide [2]. Epidemics in
the African meningitis belt are largely due to isolates of capsular
group A (MenA). Outbreaks due to isolates of serogroups W and X
(MenW and MenX) were also reported [3–10].
Currently licensed vaccines are composed of plain or conju-
gate capsular polysaccharides and directed against isolates of
serogroups A, C, Y and W. In particular, a conjugate MenA vaccine
has been recently licensed and is being used in several countries
of the meningitis belt [11]. The polysaccharide of MenB is poorly
immunogenic as it is homologous to the neural cell adhesion
∗
Corresponding author. Tel.: +33 1 45 68 84 38; fax: +33 1 45 68 83 38.
E-mail address: mktaha@pasteur.fr (M.-K. Taha).
molecules NCAMs [12,13]. No capsule-based vaccine against MenB
is available. A recombinant vaccine containing 4 components
(4CMenB) has been developed, with three novel genome-derived
proteins fHbp (factor H binding protein), NHBA (Neisseria Heparin
Binding Antigen), and NadA (Neisserial adhesin A) as well as the
outer membrane vesicles expressing porin A (PorA) serosubtype
P1.4 [14]. An approach based on sequencing of these genes to anal-
yse their polymorphism as well as on the determination of their
levels of expression by determining the subtype P1.4 and using the
Meningococcal Antigen Typing System (MATS) protocol has been
developed to predict coverage by the 4CMenB vaccine against
serogroup B meningococcal strains. It measures immunologic
cross-reactivity and quantity of expressed antigens NHBA, NadA,
and fHbp. The MATS values of these proteins are referred to as the
relative potency (RP) of a given antigen in an unknown strain in
comparison to a reference strain. The MATS also predicts killing (at
≥80% probability) of an isolate by Serum bactericidal assays (SBA)
if its RP value for any of the three vaccine antigens is higher than
a threshold called positive bactericidal threshold (PBT) [15].
The antigens in the 4CMenB vaccine may be present in
all meningococcal isolates regardless the serogroup. The recent
description of MenX outbreaks in Niger and other African countries
highlights the need for a new conjugate vaccine-based approach
to prevention [3,16]. Although a capsule-based vaccine approach
0264-410X/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.vaccine.2012.12.022