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The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C.

Abstract：

BACKGROUND:MenB-4C (Bexsero®) is a multicomponent serogroup B meningococcal vaccine. For vaccine licensure, efficacy was inferred from serum bactericidal antibody (SBA) against three antigen-specific indicator strains. The bactericidal role of antibody to the fourth vaccine antigen, Neisserial Heparin binding antigen (NHba), is incompletely understood. METHODS:We identified nine adults immunized with two or three doses of MenB-4C who had sufficient volumes of sera and >3-fold increases in SBA titer against a strain with high NHba expression, which was mismatched with the other three MenB-4C antigens that elicit SBA. Using 1month-post-immunization sera we measured the effect of depletion of anti-NHba and/or anti-Factor H binding protein (FHbp) antibodies on SBA. RESULTS:Against three strains matched with the vaccine only for NHba, depletion of anti-NHba decreased SBA titers by an average of 43-79% compared to mock-adsorbed sera (P<0.05). Despite expression of sub-family A FHbp (mismatched with the sub-family B vaccine antigen), depletion of anti-FHbp antibodies also decreased SBA by 45-64% (P<0.05). Depletion of both antibodies decreased SBA by 84-100%. Against a strain with sub-family B FHbp and expression of NHba with 100% identity to the vaccine antigen, depletion of anti-NHba decreased SBA by an average of 26%, compared to mock-adsorbed sera (P<0.0001), and depletion of anti-FHbp antibody decreased SBA by 92% (P<0.0001). CONCLUSIONS:Anti-NHba antibody can contribute to SBA elicited by MenB-4C, particularly in concert with anti-FHbp antibody. However, some high NHba-expressing strains are resistant, even with an exact match between the amino acid sequence of the vaccine and strain antigens.

journal_name

Vaccine

journal_title

Vaccine

authors

Partridge E,Lujan E,Giuntini S,Vu DM,Granoff DM

doi

10.1016/j.vaccine.2017.06.020

subject

Has Abstract

pub_date

2017-07-24 00:00:00

pages

4236-4244

issue

33

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(17)30797-1

journal_volume

35

pub_type

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