No abstract

Idiotype vaccination for follicular lymphoma is primarily being developed as remission consolidation after chemotherapy. We investigated idiotype vaccination as primary intervention for treatmentnaive indolent B-cell lymphoma and in a separate cohort as remission consolidation after chemotherapy to assess immunization-induced immune responses in relation to progression-free survival

No abstract

In B-cells, activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. AID introduces mutations in immunoglobulin variable regions (IGV) during B-cell receptor affinity maturation, but may also introduce aberrant mutations into non-immunoglobulin genes, most commonly BCL6. Follicular lymphoma (FL) B-cells constitutively express AID and undergo CSR, SHM and aberrant SHM. We have studied AID expression, the presence of SHM mutations, CSR, and aberrant SHM in BCL6 in a cohort of 75 FL patients. Whereas IgM-expressing (non-switched) FL were characterized by an expected positive correlation between AID and IGV and BCL6 mutations, isotype-switched FL showed dissociation between AID expression and aberrant SHM, and inverse correlation between SHM and AID expression. Our results unveil two manifest biological subgroups of FL and indicate that the specific dissociation between AID and SHM after isotype switch may correlate with the clinical outcome of this heterogeneous disease.

Active immunization with the idiotype of follicular lymphoma induces tumor-specific immunity. T cells induced in vivo by idiotype vaccination recognize human leukocyte antigen (HLA)-restricted hypervariable but not conserved idiotype peptides. We hypothesized that idiotype-directed T-cell immunity occurs naturally and performed a reverse immunology analysis of idiotype HLA binding in 39 follicular lymphoma patients. For every idiotype, the sum of HLA-A or -B binding scores of the 20 highest-scoring peptides was calculated for all 39 HLA types through the BIMAS algorithm. The idiotype sum score of every patient's lymphoma was compared on the respective patient's HLA type to the mean of the sum scores of the remaining 38 idiotypes. Autologous idiotypes had lower immunogenicity than allogeneicidiotypes.Differentialimmunogenicity resided predominantly in all 3 complementarity-determining regions rather than in framework peptides. IntroductionThe individual composition of potentially immunogenic epitopes of any immunoglobulin is designated as "idiotype." The idiotype is a unique feature for every B-cell clone and a tumor-specific antigen in B-cell lymphoma. Immunization of patients with follicular lymphoma (FL) against their lymphoma idiotype induces tumorspecific immunity. 1-3 When idiotype vaccination is administered as remission consolidation after conventional chemotherapy, humoral immune responses correlate with superior outcome. [4][5][6] Idiotype-specific, major histocompatibility complex (MHC) class I-restricted cytotoxic T cells circulate in lymphoma-bearing patients. 7 Immunization with recombinant idiotype F ab fragments induces idiotype-directed T cells in the majority of patients. 8,9 In the first trial testing idiotype vaccination as upfront intervention without prior cytoreductive therapy, anti-idiotype T-cell responses correlated with superior progression-free survival and with durable lymphoma remissions. 9 Peptide mapping experiments revealed that these T-cell responses are consistently directed against human leukocyte antigen (HLA) class I-restricted peptides from the complementarity-determining regions (CDRs) or against hypermutated idiotype epitopes. 8,9 These findings are in accordance with animal studies demonstrating T-cell tolerance for germlineencoded immunoglobulin sequences but responsiveness to novel idiotopes arising from junctional diversity or somatic mutations. 10 Because mouse models have also shown T cell-mediated immunosurveillance against hypervariable idiotypic peptides, 11 we sought to obtain evidence that spontaneous idiotype-directed T-cell immunity is operational in nonimmunized lymphoma patients and impairs expansion of malignant B-cell clones that express an idiotype with high immunogenicity. To test this hypothesis, we performed a "reverse immunology" bioinformatics study in 39 FL patients. Methods PatientsThe study was approved by the institutional ethics committee of University Medical Center Freiburg. All patients provided informed consent for biopsies and immunologic ...

SARS-CoV-2 variant Lambda was dominant in several South American countries, including Chile. To ascertain the efficacy of local vaccination efforts, we used pseudotyped viruses to characterize the neutralization capacity of antibodies elicited by CoronaVac (n = 53) and BNT162b2 (n = 56) in healthcare workers from Clínica Santa María and the Faculty of Medicine at Universidad de Chile, as well as in convalescent plasma from individuals infected during the first wave visiting the Hospital Clínico at Pontificia Universidad Católica (n = 30). We observed that BNT162b2 elicits higher neutralizing antibody titres than CoronaVac, with differences ranging from 7.4-fold for the ancestral spike (Wuhan-Hu-1) to 8.2-fold for the Lambda spike and 13-fold for the Delta spike. Compared with the ancestral virus, neutralization against D614G, Alpha, Gamma, Lambda and Delta variants was reduced by between 0.93-and 4.22-fold for CoronaVac, 1.04-and 2.38-fold for BNT162b2, and 1.26-and 2.67-fold for convalescent plasma. Comparative analyses among the spike structures of the different variants suggest that mutations in the spike protein from the Lambda variant, including the 246-252 deletion in an antigenic supersite at the N-terminal domain loop and L452Q/F490S within the receptor-binding domain, may account for immune escape. Interestingly, analyses using pseudotyped and whole viruses showed increased entry rates into HEK293T-ACE2 cells, but reduced replication rates in Vero-E6 cells for the Lambda variant when compared with the Alpha, Gamma and Delta variants. Our data show that inactivated virus and messenger RNA vaccines elicit different levels of neutralizing antibodies with different potency to neutralize SARS-CoV-2 variants, including the variant of interest Lambda. The emergence of SARS-CoV-2 variants of concern (VOC) and interest (VOI) has been a hallmark of the COVID-19 pandemic during 2021 1,2 . Classification of VOC and VOI by the World Health Organization has been highly dynamic with emergent SARS-CoV-2 variants such as Lambda (lineage C.37), Delta (lineage B.1.617.2), Mu (lineage B.1.621) and Omicron (B.1.1.529) being the most recently

No abstract

No abstract