Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine.

Autor: Nielsen CM; University of Oxford, Oxford, Oxfordshire, United Kingdom., Barrett JR; University of Oxford, Oxford, Oxfordshire, United Kingdom., Davis C; Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA., Fallon JK; Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard, Boston, Massachusetts, USA., Goh C; University of Oxford, Oxford, Oxfordshire, United Kingdom., Michell AR; Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard, Boston, Massachusetts, USA., Griffin C; Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA., Kwok A; University of Oxford, Oxford, Oxfordshire, United Kingdom.; Wellcome Center for Human Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom., Loos C; Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA.; Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard, Boston, Massachusetts, USA., Darko S; Vaccine Research Center, NIAID/NIH, Bethesda, Maryland, USA., Laboune F; Vaccine Research Center, NIAID/NIH, Bethesda, Maryland, USA., Tekman M; Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Diouf A; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, Maryland, USA., Miura K; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, Maryland, USA., Francica JR; Vaccine Research Center, NIAID/NIH, Bethesda, Maryland, USA., Ransier A; Vaccine Research Center, NIAID/NIH, Bethesda, Maryland, USA., Long CA; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, Maryland, USA., Silk SE; University of Oxford, Oxford, Oxfordshire, United Kingdom., Payne RO; University of Oxford, Oxford, Oxfordshire, United Kingdom., Minassian AM; University of Oxford, Oxford, Oxfordshire, United Kingdom., Lauffenburger DA; Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA., Seder RA; Vaccine Research Center, NIAID/NIH, Bethesda, Maryland, USA., Douek DC; Vaccine Research Center, NIAID/NIH, Bethesda, Maryland, USA., Alter G; Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard, Boston, Massachusetts, USA., Draper SJ; University of Oxford, Oxford, Oxfordshire, United Kingdom.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2023 Jan 24; Vol. 8 (2). Date of Electronic Publication: 2023 Jan 24.
DOI: 10.1172/jci.insight.163859
Abstrakt: Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.
Databáze: MEDLINE