Progressive decrease in the potential usefulness of meningococcal serogroup B vaccine (4CMenB, Bexsero®) in Gipuzkoa, Northern Spain.

Emilio Pérez-Trallero,Olatz Esnal,José M Marimón,Jodie Mcvernon

doi:10.1371/journal.pone.0116024

Abstract

The effectiveness of a vaccine is determined not only by the immunogenicity of its components, but especially by how widely it covers the disease-causing strains circulating in a given region. Because vaccine coverage varies over time, this study aimed to detect possible changes that could affect vaccine protection during a specific period in a southern European region. The 4CMenB vaccine is licensed for use in Europe, Canada, and Australia and is mainly directed against Neisseria meningitidis serogroup B. This vaccine contains four main immunogenic components: three recombinant proteins, FHbp, Nhba and NadA, and an outer membrane vesicle [PorA P1.4]. The allelic distribution of FHbp, Nhba, NadA, and PorA antigens in 82 invasive isolates (B and non-B serogroups) isolated from January 2008 to December 2013 were analyzed. 4CMenB was likely protective against 61.8% and 50% of serogroup B and non-B meningococci, respectively, in the entire period, but between 2012 and 2013, the predicted protection fell below 45% (42.1% for serogroup B isolates).The observed decreasing trend in the predicted protection during the 6 years of the study (Χ 2 for trend = 4.68, p = 0.03) coincided with a progressive decrease of several clonal complexes (e.g., cc11, cc32 and cc41/44), which had one or more antigens against which the vaccine would offer protection.

Highlights

Neisseria meningitidis is the first cause of bacterial meningitis and a frequent cause of severe sepsis worldwide
Aimed to detect possible changes that could affect vaccine protection during a specific period. Studies evaluating this protective effect have been performed using the MATS (Meningococcal Antigen Typing System) ELISA provided by Novartis or, as in the present study, by analyzing the allelic distribution of the four main antigens included in the 4CMenB vaccine
We assumed that the presence of fHbp B1, nhba2, nadA 1,2/3 and porA VR2 4, once expressed, is a prerequisite for the protective immune response induced by vaccination

Summary

Introduction

Neisseria meningitidis is the first cause of bacterial meningitis and a frequent cause of severe sepsis worldwide. There are effective polysaccharide conjugate vaccines against serogroups A, C, W-135 and Y, both as monovalent and as tetravalent vaccines (ACWY) but there is no conjugate vaccine against serogroup B. This is due to the similarity of the polysaccharide structure of serogroup B with the polysialic acid present in human glycoproteins, this similarity making the polysaccharide poorly immunogenic. For N. meningitidis serogroup B, there are vaccines that target porin A (PorA), one of the major outer-membrane proteins. These vaccines have been effective in outbreaks [2, 3], they are not universal as they only target specific PorA types [4]

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