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Felicori, L. F.

Publications and source records attributed to Felicori, L. F..

3 recordsLinked to original sources

Profile of the B cell receptor repertoire and antibody responses upon 17DD-YF vaccine boosting

Although the 17DD-YF vaccine is highly effective in conferring long-term immunity, recent studies suggest that booster doses may be necessary in endemic areas. In this study, we characterized the dynamics of the B cell repertoire following 17DD-YF booster vaccination and examined its impact on antibody kinetics. Using a combined approach of serological analysis and B cell receptor (BCR) sequencing, we investigated molecular features of the antibody response in four vaccinated individuals from a YFV-endemic region. Our results indicate that the booster induces a transient antibody response, with limited effect on the neutralization capacity against DENV1-4 and ZIKV. Notably, we observed a rapid clonal expansion of B cells within 14 days post-vaccination, predominantly involving IgA and IgG isotypes. However, this expansion was short-lived, with reduced magnitude and persistence of these lineages by day 28. Interestingly, some of the expanded lineages shared sequence similarity with previously characterized anti-DENV and anti-ZIKV antibodies, although further validation is required to assess their functional relevance and presence in circulating serum. Together, these findings highlight the transient nature and isotype composition of the antibody response following YFV revaccination and provide insights into the complex interplay between pre-existing immunity and recall responses in individuals living in endemic regions.

immunology↗

THE MAJOR ROLE OF JUNCTIONAL DIVERSITY IN THE HORSE ANTIBODY REPERTOIRE

The sequencing of the antibody repertoire (Rep-seq) revolutionized the diversity of antigen B cell receptor studies, allowing deep and quantitative analysis to decipher the role of adaptive immunity in health and disease. Particularly, horse (Equus caballus) polyclonal antibodies have been produced and used since the century XIX to treat and prophylaxis of diphtheria, tuberculosis, tetanus, pneumonia, and, more recently, COVID-19. However, our knowledge about the horse B cell receptors repertories is minimal. We present a deep horse antibody heavy chain repertoire (IGH) characterization of non-immunized horses using HTS technology. In this study, we obtained a mean of 248,169 unique IgM clones and 66,141 unique IgG clones from four domestic adult horses. Rarefaction analysis showed sequence coverage was between 52 and 82% in IgM and IgG isotypes. We observed that besides horses antibody can use all of the functional IGHV genes, around 80% of their antibodies use only three IGHV gene segments, and around 55% use only one IGHJ gene segment. This limited VJ diversity seems to be compensated by the junctional diversity of these antibodies. We observed that the junctional diversity in horses antibodies is highly frequent, present in more than 90% of horse antibodies. Besides this, the length of this region seems to be higher in horse antibodies than in other species. N1 and N2 nucleotides addition range from 0 to 111 nucleotides. In addition, around 45% of the antibody clones have more than ten nucleotides in both N1 and N2 junction regions. This diversity mechanism may be one of the most important in providing variability to the equine antibody repertoire. This study provides new insights regarding horse antibody composition, diversity generation, and particularities compared to other species, such as the frequency and length of N nucleotide addition. This study also points out the urgent need to better characterize TdT in horses and in other species to better understand antibody repertoire characteristics.

immunology↗

Discovery of 10,828 new putative human immunoglobulin heavy chain IGHV variants

The correct identification of immunoglobulin alleles in genome sequences is a challenge. Nevertheless, it can assist in the study of several human diseases associated with the antibody repertoire and in the development of new therapies using antibody engineering techniques. The advent of next-generation sequencing of human genomes and antibody repertoires enabled the development of several tools for the mapping and identification of new immunoglobulin (Ig) alleles. Some of these tools use 1,000 Genomes (G1K) data for new Ig alleles discovery. However, genome data from G1K present low coverage and variant call problems. Here, a computational screen of immunoglobulin alleles was carried out in the Genome Aggregation Database (gnomAD), the largest high-quality catalogue of variation from 125,748 exomes and 15,708 human genomes. A total of 10,909 putative IGHV alleles were identified, in which 10,828 of them are new and 2,024 appear at least in 6 different alleles from genomes/exomes. The IGHV2-70 was the IGHV gene segment with the largest number of variants described. The majority of the variants were found in the framework 3 and most of them are missense. Interestingly, a large number of variants were found to be population exclusive. A database integrated with a web platform was created (YGL-DB) to store and make accessible the likely new variants found. This available data can help the scientific community to validate new IGHV variants as well as it can shed light on the importance of variants in disease development and immunization protocols.

immunology↗