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Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-TFH cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM BPC) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation.
Pubmed ID: 37925510 RIS Download
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Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsAn Organization portal, Antibody supplier, Service resource,
View all literature mentionsSoftware R package provides computational framework for analyzing mutations in immunoglobulin sequences. Immunoglobulin Somatic Hypermutation Analysis.
View all literature mentionsSoftware versatile open source tool for metagenomics. Used for processing and preparing metagenomics, genomics and population genomics nucleotide sequence data.
View all literature mentionsCenter focused on understanding human health problems, including infectious diseases that require the use of nonhuman primates to develop diagnostics, therapeutics and preventive strategies. Primary research interests include developing vaccines, treatments and diagnostic tools for infectious diseases such as AIDS, tuberculosis, CMV, COVID-19, Lyme disease, and malaria. TNPRC has both biosafety level 2 and biosafety level 3 laboratories facilities to accommodate various research needs, and is the only National Primate Research Center with Regional Biosafety Laboratory.
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