The field of immunotherapy has undergone radical conceptual changes over the last decade. There are various examples of immunotherapy, including the use of monoclonal antibodies, cancer vaccines, tumor-infecting viruses, cytokines, adjuvants, and autologous T cells carrying chimeric antigen receptors (CARs) that can bind cancer-specific antigens known as adoptive immunotherapy. While a lot has been achieved in the field of T-cell immunotherapy, only a fraction of patients (20%) see lasting benefits from this mode of treatment, which is why there is a critical need to turn our attention to other immune cells. B cells have been shown to play both anti- and pro-tumorigenic roles in tumor tissue. In this review, we shed light on the dual nature of B cells in the tumor microenvironment. Furthermore, we discussed the different factors affecting the biology and function of B cells in tumors. In the third section, we described B-cell-based immunotherapies and their clinical applications and challenges. These current studies provide a springboard for carrying out future mechanistic studies to help us unleash the full potential of B cells in immunotherapy.

Summary: B‐cell memory was long characterized as isotype‐switched, somatically mutated and germinal centre (GC)‐derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B‐cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype‐switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T‐dependent versus T‐independent responses. We report that CD73 expression identifies a subset of antigen‐experienced IgM⁺ cells that share attributes of functional B‐cell memory. This subset is reduced in the spleens of T‐cell‐deficient and CD40‐deficient mice and in mixed marrow chimeras made with mutant and wild‐type marrow, the proportion of CD73⁺ IgM memory is restored in the T‐cell‐deficient donor compartment but not in the CD40‐deficient donor compartment, indicating that CD40 ligation is involved in its generation. We also report that CD40 signalling supports optimal expression of CD73 on splenic T cells and age‐associated B cells (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells, peritoneal cavity B‐1 B cells and regulatory T and B cells. Our data indicate that in addition to promoting GC‐associated memory generation during B‐cell differentiation, CD40‐signalling can influence the composition of the unswitched memory B‐cell pool. They also raise the possibility that a fraction of ABCs may represent T‐cell‐dependent IgM memory.

In the USA, two monovalent COVID-19 mRNA vaccines are primarily used for vaccination

SARS-CoV-2, a novel coronavirus, causes respiratory tract infections and other complications in affected individuals, and has resulted in numerous deaths worldwide. The unprecedented pace of its transmission worldwide, and the resultant heavy burden on healthcare systems everywhere, prompted efforts to have effective therapeutic strategies and vaccination candidates available to the global population. While aged and immunocompromised individuals form a high-risk group for COVID-19 and have severe disease outcome, the rate of infections among children has also increased with the emergence of the Omicron variant. In addition, recent reports of threatening SARS-CoV-2-associated complications in children have brought to the forefront an urgent necessity for vaccination. In this article, we discuss the current scenario of SARS-CoV-2 infections in children with a special focus on the differences in their immune system response as compared to adults. Further, we describe the various available COVID-19 vaccines, including the recent bivalent vaccines for children, in detail, intending to increase willingness for their acceptance.

Immunoglobulin A (IgA) is critical in the immune response against respiratory infections like COVID-19 and influenza

Defining how antibodies achieve broad neutralization across antigenically related flaviviruses could inform rational vaccine design. Here, we describe 3A06, a human monoclonal antibody isolated from a dengue-infected donor that potently neutralizes dengue virus serotypes 1-3 (DENV1-3) and Zika virus (ZIKV). Binding studies show that 3A06 selectively recognizes envelope (E) protein dimers, but not monomeric E, EDIII, or viral lysates, indicating strict dependence on a quaternary epitope. Affinity measurements reveal stronger binding to DENV1, DENV3, and ZIKV E dimers, with weaker binding to DENV2 and DENV4. High-resolution structural analysis of 3A06 Fab bound to a chimeric ZIKV particle shows that the antibody engages a quaternary epitope spanning three E protomers at the dimer interface. Strikingly, structural and functional analyses demonstrate that epitope recognition is dominated by the antibody light chain, with somatic mutations driving neutralization potency. While the IgG1 form neutralizes DENV1-3 and ZIKV, subclass switching to IgG3 enables neutralization of all four dengue serotypes. Structural studies using intact IgG3 with DENV support the hypothesis that the enhanced breadth is mediated by extended reach and flexibility of the IgG3 Fc-hinge scaffold. These results reveal a previously unrecognized class of flavivirus broadly neutralizing antibodies and demonstrate how antibody light chain and subclass architecture can be engineered to overcome viral diversity. Our findings provide a structural blueprint for the rational design of universal flavivirus vaccines.