{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:04:12Z","timestamp":1792695852153,"version":"4.5.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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 <jats:italic>Streptococcus pneumoniae<\/jats:italic>, Pn1-CRM<jats:sub>197<\/jats:sub>, and a recombinant influenza hemagglutinin (HA) protein vaccine. The primary Ab levels of neonatal mice immunized once with a full dose of Pn1-CRM<jats:sub>197<\/jats:sub> or HA were low. mmCT and CAF08b enhanced Pn1-specific IgG Abs elicited by fractional doses of Pn1-CRM<jats:sub>197<\/jats:sub>, 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%\u201363%) and pneumonia (50%\u201338%) in neonatal mice when combined with a half-dose of Pn1-CRM<jats:sub>197<\/jats:sub>. 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-CRM<jats:sub>197<\/jats:sub> 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.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1646677","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T05:37:45Z","timestamp":1753940265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Dose-sparing effects of novel adjuvants and aluminum hydroxide on two different vaccines in a neonatal mouse model"],"prefix":"10.3389","volume":"16","author":[{"given":"Jenny Lorena","family":"Molina Estupi\u00f1an","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poorya","family":"Foroutan Pajoohian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel 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