title: The potential of adjuvants to improve immune responses against TdaP vaccines: A preclinical evaluation of MF59 and monophosphoryl lipid A.
abstract: The successful approach of combining diphtheria, tetanus and pertussis antigens into a single vaccine has become a cornerstone of immunization programs. Yet, even if vaccination coverage is high, a resurgence of pertussis has been reported in many countries suggesting current vaccines may not provide adequate protection. To induce better tailored and more durable immune responses against pertussis vaccines different approaches have been proposed, including the use of novel adjuvants. Licensed aP vaccines contain aluminum salts, which mainly stimulate humoral immune responses and might not be ideal for protecting against Bordetella pertussis infection. Adjuvants inducing more balanced T-helper profiles or even Th1-prone responses might be more adequate. In this study, two adjuvants already approved for human use have been tested: MF59 emulsion and the combination of aluminum hydroxide with the Toll-Like Receptor 4 agonist MPLA. Adjuvanticity was evaluated in a mouse model using a TdaP vaccine containing three B. pertussis antigens: genetically detoxified pertussis toxin (PT-9K/129G), filamentous hemagglutinin (FHA) and pertactin (PRN) The physico-chemical compatibility of TdaP antigens with the proposed adjuvants, together with a quicker onset and changed quality of the antibody responses, fully supports the replacement of aluminum salts with a new adjuvant to enhance aP vaccines immunogenicity.
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l. (a GSK company), Via Fiorentina 1, 53100 Siena, Italy; Università degli Studi di Padova, Via Ugo Bassi 58b, 35121 Padova, Italy. Electronic address: va.agnolon@gmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Agnolon
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l. (a GSK company), Via Fiorentina 1, 53100 Siena, Italy; Università di Siena, Via Aldo Moro 2, 53100 Siena, Italy. Electronic address: cristina.x.bruno@gsk.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bruno
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l. (a GSK company), Via Fiorentina 1, 53100 Siena, Italy. Electronic address: rosanna.x.leuzzi@gsk.com.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Leuzzi
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l. (a GSK company), Via Fiorentina 1, 53100 Siena, Italy. Electronic address: bruno.x.galletti@gsk.com.
authors.forename: Bruno
authors.initials: B
authors.lastname: Galletti
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l. (a GSK company), Via Fiorentina 1, 53100 Siena, Italy. Electronic address: ugo.doro@novartis.com.
authors.forename: Ugo
authors.initials: U
authors.lastname: D'Oro
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l. (a GSK company), Via Fiorentina 1, 53100 Siena, Italy. Electronic address: mariagrazia.x.pizza@gsk.com.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l. (a GSK company), Via Fiorentina 1, 53100 Siena, Italy. Electronic address: anja.k.seubert@gsk.com.
authors.forename: Anja
authors.initials: A
authors.lastname: Seubert
authors.affiliation: GlaxoSmithKline Vaccines (former Novartis Vaccines), 350 Massachusetts Ave, Cambridge, 02139 MA, USA. Electronic address: derek.ohagan@novartis.com.
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l. (a GSK company), Via Fiorentina 1, 53100 Siena, Italy. Electronic address: barbara.c.baudner@gsk.com.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Baudner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000534:Alum Compounds / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology; D016466:CHO Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003412:Cricetulus; D004167:Diphtheria Toxin / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin / Q000276:immunology; D011136:Polysorbates / Q000008:administration & dosage* / Q000737:chemistry; D013185:Squalene / Q000008:administration & dosage* / Q000737:chemistry; D014709:Vero Cells
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004167:Diphtheria Toxin; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D007074:Immunoglobulin G; D008050:Lipid A; C089950:MF59 oil emulsion; D011136:Polysorbates; C041524:aluminum sulfate; D013185:Squalene; D037342:Pertussis Toxin; C048436:monophosphoryl lipid A
keywords: Adjuvants; Mouse model; Pertussis; Vaccine formulation