Characterization of vaccine antigens of meningococcal serogroup W isolates from Ghana and Burkina Faso from 2003 to 2009

Abstract

Neisseria meningitidis is a major cause of bacterial meningitis and a considerable health problem in the 25 countries of the ‘African Meningitis Belt’ that extends from Senegal in West Africa to Ethiopia in the East. Approximately 80% of cases of meningococcal meningitis in Africa have been caused by strains belonging to capsular serogroup A. After the introduction of a serogroup A conjugate polysaccharide vaccine, MenAfriVac ™, that began in December 2010, the incidence of meningitis due to serogroup A has markedly declined in this region. Currently, serogroup W of N. meningitidis accounts for the majority of cases. Vaccines based on sub-capsular antigens, such as Generalized Modules for Membrane Antigens (GMMA), are under investigation for use in Africa. To analyse the antigenic properties of a serogroup W wave of colonisation and disease, we investigated the molecular diversity of the protein vaccine antigens PorA, Neisserial Adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and factor H binding protein (fHbp) of 31 invasive and carriage serogroup W isolates collected as part of a longitudinal study from Ghana and Burkina Faso between 2003 and 2009. We found that the isolates all expressed fHbp variant 2 ID 22 or 23, differing from each other by only one amino acid, and a single PorA subtype of P1.5,2. Of the isolates, 49% had a functional nhbA gene and 100% had the nadA allele 3, which contained the insertion sequence IS1301 in five isolates. Of the W isolates tested, 41% had high fHbp expression when compared with a reference serogroup B strain, known to be a high expresser of fHbp variant 2. Our results indicate that in this collection of serogroup W isolates, there is limited antigenic diversification over time of vaccine candidate outer membrane proteins (OMP), thus making them promising candidates for inclusion in a protein-based vaccine against meningococcal meningitis for Africa.

Contribution of factor H-Binding protein sequence to the cross-reactivity of meningococcal native outer membrane vesicle vaccines with over-expressed fHbp variant group 1

“…meningitidis NOMV. We selected the fHbp peptides belonging to variant group 1, carrying either the fH-contact consensus sequence, or a less common sequence, and identified as the most prevalent among African case-related clinical isolates: ID 5, ID 9, and ID 74 [ 16 , 30 ]. ID 9 is one of the peptides that contain the fH-binding site consensus sequence.…”

“…We tested the immunogenicity in mice of NOMV derived from an African W meningococcal strain, devoid of wild type v.2 fHbp and capsule biosynthesis, and over-expressing one out of four different fHbp v.1 ID types (ID 1, ID 5, ID 9, or ID 74), relevant among currently circulating African invasive isolates and/or expressed in NOMV in previous studies [ 16 , 21 , 30 ]. Among the fHbp IDs selected, ID 9 contained the fH-binding site consensus sequence.…”

[Meningococcal meningitis: a case of serogroup W in an underage migrant]

“…All' esame neurologico appariva sonnolenta, ma reattiva e risvegliabile, con presenza Nella Meningitis Belt, dopo l'introduzione del vaccino coniugato contro il meningococco A dal dicembre 2010, l'incidenza di meningite dovuta a tale sierogruppo è marcatamente diminuita e, attualmente, il W rappresenta la maggioranza dei casi [15].…”

“…Infatti, sia in Europa sia, in scala più ampia, a livello mondiale, emergono casi singoli o focolai attribuibili a sierogruppi diversi da quelli endemici, considerati propri di una determinata area geografica. Questo può avvenire per propagazione di casi da nuovi focolai (di cui gli eventi di mass gathering possono essere fattori favorenti) [14,21,22] o anche in seguito a interventi di prevenzione e sanità pubblica, come ad esempio l'introduzione di vaccinazioni di massa contro un dato sierogruppo, con la conseguente emergenza di altri ceppi [15][16][17]. L' epidemiologia del meningococco cambia e, anche in corrispondenza della Meningitis Belt, sembra che il sierogruppo W si stia affermando in maniera concreta, come suggeriscono i casi verificatisi e gli studi sulla sierotipizzazione nei portatori.…”

Serogroup A meningococcal conjugate vaccines in Africa

“…The antigens used in a recently licensed serogroup B vaccine (Bexsero) have shown potential of protecting against serogroup X disease in the meningitis belt [103]. Outer membrane vesicle vaccines using native African strains [104,105] or genetically engineered strains [106,107] have also shown promising results.…”