Despite raising the bar of clinical efficacy, immunologically targeted agents raise new challenges to conventional drug development paradigms by highlighting the limited relevance of assessing standard pharmacokinetics (PK) and pharmacodynamics (PD). The efficacy of PD-1/PD-L1 targeted therapies in addition to anti-CTLA-4 solidifies immunotherapy as a modality to add to the anticancer arsenal. Journal for ImmunoTherapy of Cancer volume 4, Article number: 15 ( 2016) on behalf of the Cancer Immunotherapy Trials Network (CITN).10.1016/j.vaccine.2007.07.Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials Influenza vaccine: the challenge of antigenic drift. Historical H1N1 influenza virus imprinting increases vaccine protection by influencing the activity and sustained production of antibodies elicited at vaccination in ferrets. 10.1038/nm.4224įrancis ME, McNeil M, Dawe NJ, Foley MK, King ML, Ross TM, et al. Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination. Lee J, Boutz DR, Chromikova V, Joyce MG, Vollmers C, Leung K, et al. Global mortality associated with seasonal influenza epidemics: New burden estimates and predictors from the GLaMOR Project. Paget J, Spreeuwenberg P, Charu V, Taylor RJ, Iuliano AD, Bresee J, et al. (C) Sequence analysis of heavy and light chain private and public mAbs. For each mAb, the minimal concentration needed to inhibit hemagglutination is reported in the corresponding tables and expressed in microgram per milliliter. All mAbs were tested across a 2-fold serial dilution series, starting from 10 μg/mL. (B) HAI activity of mAbs against the corresponding H1 (CA/09), H3 (HK/14) and IBV (Brisb/08) vaccine strains. The area under the curve (AUC) was calculated from each dilution curve and reported on the heatmap table. All the mAbs were tested at different 3-fold dilutions, starting from 20 μg/mL. For H1-, H3- and IBV-specific mAbs the HA1 and HA monomer from CA/09, WI/05 and MA/12 were used, respectively. Binding activity was also tested against COBRA H1N1 P1, X3 and X6 and H3N2 T10 and T11 rHA, the chimeric cH6/1, cH5/3 and cH7/3 rHAs, a truncated HA1 rHA and an rHA monomer. Binding of mAbs was evaluated against a panel of H1, H3 and IBV rHAs from historical seasonal, pandemic (CA/09) and post-pandemic (Mich/15 and Brisb/18) strains. (A) Synopsis of H1-, H3-, and IBV-specific human mAbs binding against H1N1, H3N2 and IBV rHA. Collectively, this high-resolution antibody repertoire analysis demonstrated the impact evolution can have on BCRs in response to influenza virus vaccination, which can guide future universal influenza prophylactic approaches. Binding profiles of one private and three public PBs confirmed they were all subtype-specific, cross-reactive hemagglutinin (HA) head-directed antibodies. Approximately 60% (10/17) of participants experienced convergent evolution, possessing public PBs that were elicited independently in multiple participants. In some participants, a single expanded clonotype accounted for ~22% of their PB BCR repertoire. A combination of Immune Repertoire Capture (IRCTM) technology and IgG sequencing was performed on ~7,800 plasmablast (PB) cells and preferential IgG heavy-light chain pairings were investigated. In this study, PBMCs were collected from 17 human participants vaccinated with the split-inactivated influenza virus vaccine during the 2016-2017 influenza season. Recent advances in high-throughput single cell sequencing have opened up new avenues into the investigation of B cell receptor (BCR) repertoires.
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