biostudies-literatureMadden PJHoward Hughes Medical InstituteNIAID NIH HHSNIH HHS997-1014.e11https://www.ebi.ac.uk/biostudies/studies/S-EPMC12060733biostudies-literatureUnknown58(4)Rare naive B cells have special pathogen-recognition features that enable outsized contributions to protective immunity but infrequently participate in immune responses. We investigatee how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (<1-in-50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs) compared with other conditions. All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP but scarce BG18-like B cells. Following homologousImmunityDiverse priming outcomes under conditions of very rare precursor B cells.PMC12060733R37 AI125068S10 OD025052UM1 AI144462P51 OD011132S10 OD026799Marina-Zarate EIrvine DJSchultze SGeorgeson EShil MMaiorino LLewis VRZhou ACrotty SPhelps NAlavi NLiguori ASteichen JMRodrigues KASchief WRPradhan APai Kasturi SMadden PJMichaels KKNi KMelo MBLopez PGShields KLu DFlynn CLemnios AXiao SKubitz MPhung IBosinger SESaha SCarnathan DGSmith MLLim DMetz AEskandarzadeh SGregory JRodriguez OLHealy BSBen-Akiva EPinney WWatson CTUpadhyay AASilvestri GKalyuzhiny OfalseDiverse priming outcomes under conditions of very rare precursor B cells.Rare naive B cells have special pathogen-recognition features that enable outsized contributions to protective immunity but infrequently participate in immune responses. We investigatee how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (<1-in-50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs) compared with other conditions. All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP but scarce BG18-like B cells. Following homologous2025-01-01T00:00:00Z2025 Apr2026-06-02T13:09:49.505Z2026-04-18T03:11:23.191ZS-EPMC120607334016899210.1016/j.immuni.2025.03.003