Cargando…
A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine
MenB-4C (Bexsero; GlaxoSmithKline Biologicals) is a licensed meningococcal vaccine for capsular B strains. The vaccine contains detergent-extracted outer membrane vesicles (dOMV) and three recombinant proteins, of which one is factor H binding protein (FHbp). In previous studies, overexpression of F...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581866/ https://www.ncbi.nlm.nih.gov/pubmed/31213564 http://dx.doi.org/10.1128/mBio.01231-19 |
_version_ | 1783428231198670848 |
---|---|
author | Beernink, Peter T. Vianzon, Vianca Lewis, Lisa A. Moe, Gregory R. Granoff, Dan M. |
author_facet | Beernink, Peter T. Vianzon, Vianca Lewis, Lisa A. Moe, Gregory R. Granoff, Dan M. |
author_sort | Beernink, Peter T. |
collection | PubMed |
description | MenB-4C (Bexsero; GlaxoSmithKline Biologicals) is a licensed meningococcal vaccine for capsular B strains. The vaccine contains detergent-extracted outer membrane vesicles (dOMV) and three recombinant proteins, of which one is factor H binding protein (FHbp). In previous studies, overexpression of FHbp in native OMV (NOMV) with genetically attenuated endotoxin (LpxL1) and/or by the use of mutant FHbp antigens with low factor H (FH) binding increased serum bactericidal antibody (SBA) responses. In this study, we immunized 13 infant macaques with 2 doses of NOMV with overexpressed mutant (R41S) FHbp with low binding to macaque FH (NOMV-FHbp). Control macaques received MenB-4C (n = 13) or aluminum hydroxide adjuvant alone (n = 4). NOMV-FHbp elicited a 2-fold higher IgG anti-FHbp geometric mean titer (GMT) than MenB-4C (P = 0.003), and the anti-FHbp repertoire inhibited binding of FH to FHbp, whereas anti-FHbp antibodies to MenB-4C enhanced FH binding. MenB-4C elicited a 10-fold higher GMT against strain NZ98/254, which was used to prepare the dOMV component, whereas NOMV-FHbp elicited an 8-fold higher GMT against strain H44/76, which was the parent of the mutant NOMV-FHbp vaccine strain. Against four strains with PorA mismatched to both of the vaccines and different FHbp sequence variants, NOMV-FHbp elicited 6- to 14-fold higher SBA GMTs than MenB-4C (P ≤ 0.0002). Two of 13 macaques immunized with MenB-4C but 0 of 17 macaques immunized with NOMV-FHbp or adjuvant developed serum anti-FH autoantibodies (P = 0.18). Thus, the mutant NOMV-FHbp approach has the potential to elicit higher and broader SBA responses than a licensed group B vaccine that contains wild-type FHbp that binds FH. The mutant NOMV-FHbp also might pose less of a risk of eliciting anti-FH autoantibodies. |
format | Online Article Text |
id | pubmed-6581866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-65818662019-06-24 A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine Beernink, Peter T. Vianzon, Vianca Lewis, Lisa A. Moe, Gregory R. Granoff, Dan M. mBio Research Article MenB-4C (Bexsero; GlaxoSmithKline Biologicals) is a licensed meningococcal vaccine for capsular B strains. The vaccine contains detergent-extracted outer membrane vesicles (dOMV) and three recombinant proteins, of which one is factor H binding protein (FHbp). In previous studies, overexpression of FHbp in native OMV (NOMV) with genetically attenuated endotoxin (LpxL1) and/or by the use of mutant FHbp antigens with low factor H (FH) binding increased serum bactericidal antibody (SBA) responses. In this study, we immunized 13 infant macaques with 2 doses of NOMV with overexpressed mutant (R41S) FHbp with low binding to macaque FH (NOMV-FHbp). Control macaques received MenB-4C (n = 13) or aluminum hydroxide adjuvant alone (n = 4). NOMV-FHbp elicited a 2-fold higher IgG anti-FHbp geometric mean titer (GMT) than MenB-4C (P = 0.003), and the anti-FHbp repertoire inhibited binding of FH to FHbp, whereas anti-FHbp antibodies to MenB-4C enhanced FH binding. MenB-4C elicited a 10-fold higher GMT against strain NZ98/254, which was used to prepare the dOMV component, whereas NOMV-FHbp elicited an 8-fold higher GMT against strain H44/76, which was the parent of the mutant NOMV-FHbp vaccine strain. Against four strains with PorA mismatched to both of the vaccines and different FHbp sequence variants, NOMV-FHbp elicited 6- to 14-fold higher SBA GMTs than MenB-4C (P ≤ 0.0002). Two of 13 macaques immunized with MenB-4C but 0 of 17 macaques immunized with NOMV-FHbp or adjuvant developed serum anti-FH autoantibodies (P = 0.18). Thus, the mutant NOMV-FHbp approach has the potential to elicit higher and broader SBA responses than a licensed group B vaccine that contains wild-type FHbp that binds FH. The mutant NOMV-FHbp also might pose less of a risk of eliciting anti-FH autoantibodies. American Society for Microbiology 2019-06-18 /pmc/articles/PMC6581866/ /pubmed/31213564 http://dx.doi.org/10.1128/mBio.01231-19 Text en Copyright © 2019 Beernink et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Beernink, Peter T. Vianzon, Vianca Lewis, Lisa A. Moe, Gregory R. Granoff, Dan M. A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine |
title | A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine |
title_full | A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine |
title_fullStr | A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine |
title_full_unstemmed | A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine |
title_short | A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine |
title_sort | meningococcal outer membrane vesicle vaccine with overexpressed mutant fhbp elicits higher protective antibody responses in infant rhesus macaques than a licensed serogroup b vaccine |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581866/ https://www.ncbi.nlm.nih.gov/pubmed/31213564 http://dx.doi.org/10.1128/mBio.01231-19 |
work_keys_str_mv | AT beerninkpetert ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT vianzonvianca ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT lewislisaa ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT moegregoryr ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT granoffdanm ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT beerninkpetert meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT vianzonvianca meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT lewislisaa meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT moegregoryr meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT granoffdanm meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine |