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

ABSTRACT 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, overexpres...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Peter T. Beernink, Vianca Vianzon, Lisa A. Lewis, Gregory R. Moe, Dan M. Granoff
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	factor H binding protein Neisseria meningitidis outer membrane vesicles nonhuman primate vaccines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/58660d846af844aab10e3e33c323b3b9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:58660d846af844aab10e3e33c323b3b9
record_format	dspace
spelling	oai:doaj.org-article:58660d846af844aab10e3e33c323b3b92021-11-15T15:55:23ZA Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine10.1128/mBio.01231-192150-7511https://doaj.org/article/58660d846af844aab10e3e33c323b3b92019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01231-19https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE There are two licensed meningococcal capsular B vaccines. Both contain recombinant factor H binding protein (FHbp), which can bind to host complement factor H (FH). The limitations of these vaccines include a lack of protection against some meningococcal strains and the potential to elicit autoantibodies to FH. We immunized infant macaques with a native outer membrane vesicle (NOMV) vaccine with genetically attenuated endotoxin and overproduced mutant FHbp with low binding to FH. The NOMV-FHbp vaccine stimulated higher levels of protective serum antibodies than a licensed meningococcal group B vaccine against five of six genetically diverse meningococcal strains tested. Two of 13 macaques immunized with the licensed vaccine, which contains FHbp that binds macaque FH, but 0 of 17 macaques given NOMV-FHbp or the negative control developed serum anti-FH autoantibodies Thus, in a relevant nonhuman primate model, the NOMV-FHbp vaccine elicited greater protective antibodies than the licensed vaccine and may pose less of a risk of anti-FH autoantibody.Peter T. BeerninkVianca VianzonLisa A. LewisGregory R. MoeDan M. GranoffAmerican Society for Microbiologyarticlefactor H binding proteinNeisseria meningitidisouter membrane vesiclesnonhuman primatevaccinesMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	factor H binding protein Neisseria meningitidis outer membrane vesicles nonhuman primate vaccines Microbiology QR1-502
spellingShingle	factor H binding protein Neisseria meningitidis outer membrane vesicles nonhuman primate vaccines Microbiology QR1-502 Peter T. Beernink Vianca Vianzon Lisa A. Lewis Gregory R. Moe Dan M. Granoff 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
description	ABSTRACT 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. IMPORTANCE There are two licensed meningococcal capsular B vaccines. Both contain recombinant factor H binding protein (FHbp), which can bind to host complement factor H (FH). The limitations of these vaccines include a lack of protection against some meningococcal strains and the potential to elicit autoantibodies to FH. We immunized infant macaques with a native outer membrane vesicle (NOMV) vaccine with genetically attenuated endotoxin and overproduced mutant FHbp with low binding to FH. The NOMV-FHbp vaccine stimulated higher levels of protective serum antibodies than a licensed meningococcal group B vaccine against five of six genetically diverse meningococcal strains tested. Two of 13 macaques immunized with the licensed vaccine, which contains FHbp that binds macaque FH, but 0 of 17 macaques given NOMV-FHbp or the negative control developed serum anti-FH autoantibodies Thus, in a relevant nonhuman primate model, the NOMV-FHbp vaccine elicited greater protective antibodies than the licensed vaccine and may pose less of a risk of anti-FH autoantibody.
format	article
author	Peter T. Beernink Vianca Vianzon Lisa A. Lewis Gregory R. Moe Dan M. Granoff
author_facet	Peter T. Beernink Vianca Vianzon Lisa A. Lewis Gregory R. Moe Dan M. Granoff
author_sort	Peter T. Beernink
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_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_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_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
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/58660d846af844aab10e3e33c323b3b9
work_keys_str_mv	AT petertbeernink ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT viancavianzon ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT lisaalewis ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT gregoryrmoe ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT danmgranoff ameningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT petertbeernink meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT viancavianzon meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT lisaalewis meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT gregoryrmoe meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine AT danmgranoff meningococcaloutermembranevesiclevaccinewithoverexpressedmutantfhbpelicitshigherprotectiveantibodyresponsesininfantrhesusmacaquesthanalicensedserogroupbvaccine
_version_	1718427218429870080

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

Ejemplares similares