Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model
Childhood vaccination provides protection against infectious diseases, but multiple vaccinations are required to achieve this. In situations like influenza epidemics or COVID-19 pandemic, vaccine demands may exceed production capacity, highlighting the need for dose-sparing strategies. Adjuvants can...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1646677/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850074803900252160 |
|---|---|
| author | Jenny Lorena Molina Estupiñan Jenny Lorena Molina Estupiñan Poorya Foroutan Pajoohian Poorya Foroutan Pajoohian Gabriel Kristian Pedersen Dennis Christensen Serena Marchi Emanuele Montomoli Emanuele Montomoli Stefanía P. Bjarnarson Stefanía P. Bjarnarson Ingileif Jonsdottir Ingileif Jonsdottir Audur Anna Aradottir Pind Audur Anna Aradottir Pind |
| author_facet | Jenny Lorena Molina Estupiñan Jenny Lorena Molina Estupiñan Poorya Foroutan Pajoohian Poorya Foroutan Pajoohian Gabriel Kristian Pedersen Dennis Christensen Serena Marchi Emanuele Montomoli Emanuele Montomoli Stefanía P. Bjarnarson Stefanía P. Bjarnarson Ingileif Jonsdottir Ingileif Jonsdottir Audur Anna Aradottir Pind Audur Anna Aradottir Pind |
| author_sort | Jenny Lorena Molina Estupiñan |
| collection | DOAJ |
| description | Childhood vaccination provides protection against infectious diseases, but multiple vaccinations are required to achieve this. In situations like influenza epidemics or COVID-19 pandemic, vaccine demands may exceed production capacity, highlighting the need for dose-sparing strategies. Adjuvants can boost and modulate immune responses to vaccines and could reduce the antigen doses needed to confer protection. Herein we evaluated the dose-sparing effects of the novel adjuvants dmLT, mmCT, CAF01, and CAF08b and alum (aluminum hydroxide) on primary neonatal antibody (Ab) response to a conjugate vaccine against Streptococcus pneumoniae, Pn1-CRM197, and a recombinant influenza hemagglutinin (HA) protein vaccine. The primary Ab levels of neonatal mice immunized once with a full dose of Pn1-CRM197 or HA were low. mmCT and CAF08b enhanced Pn1-specific IgG Abs elicited by fractional doses of Pn1-CRM197, providing eightfold dose sparing of the vaccine, whereas dmLT and CAF01 provided fivefold and twofold dose sparing, respectively. These adjuvants elicited protective Pn1-specific Ab levels against bacteremia (91%–63%) and pneumonia (50%–38%) in neonatal mice when combined with a half-dose of Pn1-CRM197. In addition, mmCT, CAF01, and CAF08b enhanced the persistence of Pn1-specific IgG Ab-secreting cells (ASCs) in bone marrow compared with a full dose of vaccine only. With the influenza HA vaccine, CAF08b provided 40-fold dose sparing, while CAF01 and mmCT provided twofold dose sparing. CAF08b induced the micro-neutralization (MN) titers above protective levels in 100% and 86% of mice receiving 1/8 and 1/40 of HA dose, respectively, and CAF01 in 88% and 50% of mice receiving 1/4 and 1/8 dose of HA, respectively, whereas only 38% of mice receiving a full-dose HA without adjuvant reached the protective MN levels. Furthermore, these adjuvants provided cross-protective Abs and ASCs against a closely related heterologous influenza strain. In contrast, aluminum hydroxide did not provide any dose-sparing effects. Collectively, our results demonstrate that mmCT, CAF01, and CAF08b enhanced the protective humoral responses and had large dose-sparing effects on both Pn1-CRM197 and HA vaccines, although the adjuvant effect was clearly vaccine-dependent. The results support the potential use of safe adjuvants in situations when vaccine production capacity is limited, including vaccination of pediatric populations that may be of high risk. |
| format | Article |
| id | doaj-art-55bbf5fddb4046929ff95b8b7be7fe81 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-55bbf5fddb4046929ff95b8b7be7fe812025-08-20T02:46:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16466771646677Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse modelJenny Lorena Molina Estupiñan0Jenny Lorena Molina Estupiñan1Poorya Foroutan Pajoohian2Poorya Foroutan Pajoohian3Gabriel Kristian Pedersen4Dennis Christensen5Serena Marchi6Emanuele Montomoli7Emanuele Montomoli8Stefanía P. Bjarnarson9Stefanía P. Bjarnarson10Ingileif Jonsdottir11Ingileif Jonsdottir12Audur Anna Aradottir Pind13Audur Anna Aradottir Pind14Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, IcelandDepartment of Immunology, Landspitali, the National University Hospital of Iceland, Reykjavík, IcelandFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, IcelandDepartment of Immunology, Landspitali, the National University Hospital of Iceland, Reykjavík, IcelandCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkDepartment of Molecular and Developmental Medicine, University of Siena, Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Siena, ItalyVisMederi, Siena, ItalyFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, IcelandDepartment of Immunology, Landspitali, the National University Hospital of Iceland, Reykjavík, IcelandFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, IcelandDepartment of Immunology, Landspitali, the National University Hospital of Iceland, Reykjavík, IcelandFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, IcelandDepartment of Immunology, Landspitali, the National University Hospital of Iceland, Reykjavík, IcelandChildhood vaccination provides protection against infectious diseases, but multiple vaccinations are required to achieve this. In situations like influenza epidemics or COVID-19 pandemic, vaccine demands may exceed production capacity, highlighting the need for dose-sparing strategies. Adjuvants can boost and modulate immune responses to vaccines and could reduce the antigen doses needed to confer protection. Herein we evaluated the dose-sparing effects of the novel adjuvants dmLT, mmCT, CAF01, and CAF08b and alum (aluminum hydroxide) on primary neonatal antibody (Ab) response to a conjugate vaccine against Streptococcus pneumoniae, Pn1-CRM197, and a recombinant influenza hemagglutinin (HA) protein vaccine. The primary Ab levels of neonatal mice immunized once with a full dose of Pn1-CRM197 or HA were low. mmCT and CAF08b enhanced Pn1-specific IgG Abs elicited by fractional doses of Pn1-CRM197, providing eightfold dose sparing of the vaccine, whereas dmLT and CAF01 provided fivefold and twofold dose sparing, respectively. These adjuvants elicited protective Pn1-specific Ab levels against bacteremia (91%–63%) and pneumonia (50%–38%) in neonatal mice when combined with a half-dose of Pn1-CRM197. In addition, mmCT, CAF01, and CAF08b enhanced the persistence of Pn1-specific IgG Ab-secreting cells (ASCs) in bone marrow compared with a full dose of vaccine only. With the influenza HA vaccine, CAF08b provided 40-fold dose sparing, while CAF01 and mmCT provided twofold dose sparing. CAF08b induced the micro-neutralization (MN) titers above protective levels in 100% and 86% of mice receiving 1/8 and 1/40 of HA dose, respectively, and CAF01 in 88% and 50% of mice receiving 1/4 and 1/8 dose of HA, respectively, whereas only 38% of mice receiving a full-dose HA without adjuvant reached the protective MN levels. Furthermore, these adjuvants provided cross-protective Abs and ASCs against a closely related heterologous influenza strain. In contrast, aluminum hydroxide did not provide any dose-sparing effects. Collectively, our results demonstrate that mmCT, CAF01, and CAF08b enhanced the protective humoral responses and had large dose-sparing effects on both Pn1-CRM197 and HA vaccines, although the adjuvant effect was clearly vaccine-dependent. The results support the potential use of safe adjuvants in situations when vaccine production capacity is limited, including vaccination of pediatric populations that may be of high risk.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1646677/fullimmunizationneonatesadjuvantsdose-sparingantibodiesantibody-secreting cells |
| spellingShingle | Jenny Lorena Molina Estupiñan Jenny Lorena Molina Estupiñan Poorya Foroutan Pajoohian Poorya Foroutan Pajoohian Gabriel Kristian Pedersen Dennis Christensen Serena Marchi Emanuele Montomoli Emanuele Montomoli Stefanía P. Bjarnarson Stefanía P. Bjarnarson Ingileif Jonsdottir Ingileif Jonsdottir Audur Anna Aradottir Pind Audur Anna Aradottir Pind Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model Frontiers in Immunology immunization neonates adjuvants dose-sparing antibodies antibody-secreting cells |
| title | Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model |
| title_full | Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model |
| title_fullStr | Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model |
| title_full_unstemmed | Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model |
| title_short | Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model |
| title_sort | dose sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model |
| topic | immunization neonates adjuvants dose-sparing antibodies antibody-secreting cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1646677/full |
| work_keys_str_mv | AT jennylorenamolinaestupinan dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT jennylorenamolinaestupinan dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT pooryaforoutanpajoohian dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT pooryaforoutanpajoohian dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT gabrielkristianpedersen dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT dennischristensen dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT serenamarchi dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT emanuelemontomoli dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT emanuelemontomoli dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT stefaniapbjarnarson dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT stefaniapbjarnarson dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT ingileifjonsdottir dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT ingileifjonsdottir dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT audurannaaradottirpind dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel AT audurannaaradottirpind dosesparingeffectsofnoveladjuvantsandaluminumhydroxideontwodifferentvaccinesinaneonatalmousemodel |