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

Elizabeth Partridge, Eduardo Lujan, Serena Giuntini, David M. Vu, Dan M. Granoff

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 1 month-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.

Original languageEnglish (US)
Pages (from-to)4236-4244
Number of pages9
JournalVaccine
Volume35
Issue number33
DOIs
StatePublished - Jul 24 2017
Externally publishedYes

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heparin
Heparin
serotypes
Vaccines
vaccines
antigens
Antigens
antibodies
Antibodies
Complement Factor H
Serum
binding proteins
Carrier Proteins
Serogroup
Meningococcal Vaccines
Licensure

Keywords

  • Complement
  • Factor H binding protein
  • FHbp
  • Neisseria meningitidis
  • Neisserial Heparin binding antigen
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C. / Partridge, Elizabeth; Lujan, Eduardo; Giuntini, Serena; Vu, David M.; Granoff, Dan M.

In: Vaccine, Vol. 35, No. 33, 24.07.2017, p. 4236-4244.

Research output: Contribution to journalArticle

Partridge, Elizabeth ; Lujan, Eduardo ; Giuntini, Serena ; Vu, David M. ; Granoff, Dan M. / The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C. In: Vaccine. 2017 ; Vol. 35, No. 33. pp. 4236-4244.
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abstract = "Background MenB-4C (Bexsero{\circledR}) 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 1 month-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.",
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T1 - The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C

AU - Partridge, Elizabeth

AU - Lujan, Eduardo

AU - Giuntini, Serena

AU - Vu, David M.

AU - Granoff, Dan M.

PY - 2017/7/24

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N2 - 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 1 month-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.

AB - 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 1 month-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.

KW - Complement

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KW - Neisseria meningitidis

KW - Neisserial Heparin binding antigen

KW - Vaccine

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