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Many Gram-negative bacterial polysaccharide vaccines, including the tetravalent meningococcal conjugate vaccines (MCV4) and typhoid Vi polysaccharide vaccines, do not incorporate adjuvants. The immunogenicity of typhoid vaccines is due to the presence of associated TLR4 ligands in these vaccines. Because the immunogenicity of MCV4 is poor and requires boosters, I hypothesized that TLR4 ligands are absent in MCV4 and that incorporation of a TLR4 ligand\u2013based adjuvant would improve their immunogenicity. Consistent with this hypothesis, two Food and Drug Administration\u2013approved MCV4 vaccines, MENVEO and MenQuadfi, lack TLR4 ligands. Admixing monophosphoryl lipid A, a TLR4 ligand\u2013based adjuvant formulation named \u201cTurbo\u201d with MCV4 induced significantly improved IgM and IgG responses to all four meningococcal serogroup polysaccharides in adult and aged mice after a single immunization. Furthermore, in infant mice, a single booster was sufficient to promote a robust IgG response and 100% seroconversion when MCV4 was adjuvanted with Turbo. Turbo upregulated the expression of the costimulatory molecules CD40 and CD86 on B cells, and Turbo-driven adjuvanticity is lost in mice deficient in CD40 and CD86. These data suggest that Turbo induces the required costimulatory molecules for its adjuvant activity and that incorporation of Turbo could make bacterial polysaccharide vaccines more immunogenic, minimize booster requirements, and be cost-effective, particularly for those individuals in low- and middle-income and disease-endemic countries.<\/jats:p>","DOI":"10.4049\/immunohorizons.2400013","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T15:14:18Z","timestamp":1713280458000},"page":"317-325","source":"Crossref","is-referenced-by-count":6,"title":["Monophosphoryl Lipid A\u2013based Adjuvant to Promote the Immunogenicity of Multivalent Meningococcal Polysaccharide Conjugate Vaccines"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8092-514X","authenticated-orcid":false,"given":"Kishore R","family":"Alugupalli","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA"},{"name":"TurboVax Inc. , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"2025010608551642400_r1","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1016\/j.vaccine.2019.04.020","article-title":"Case fatality rates of invasive meningococcal disease by serogroup and age: a systematic review and meta-analysis","volume":"37","author":"Wang","year":"2019","journal-title":"Vaccine"},{"key":"2025010608551642400_r2","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jadohealth.2016.04.012","article-title":"The global evolution of meningococcal epidemiology following the introduction of meningococcal vaccines","volume":"59","author":"Pelton","year":"2016","journal-title":"J. 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