Immunity

The regular emergence of influenza strains with pandemic potential necessitates vaccines that elicit protective immune responses across genetically diverse human populations. A critical but understudied factor is how germline-encoded variation in immunoglobulin genes shapes the development of neutralizing antibodies. Here, by combining personalized immunoglobulin genotyping with high-throughput p…

Immunological mechanisms regulating HIV rebound after antiretroviral therapy (ART) interruption remain unclear. We examined relationships between host factors, HIV reservoir, and HIV time-to-rebound after analytical treatment interruption (ATI) by characterizing pre-ATI peripheral blood mononuclear cells (PBMCs) from 75 ART-suppressed people with HIV (PWH) using high-parameter methods. Across int…

The human antibody repertoire includes reactivity toward a broad array of carbohydrate antigens associated with commensal microflora and pathogenic organisms. Here, we examined the ontogeny and diversity of the human anti-glycan repertoire. Antibodies reactive with group A Streptococcus cell wall carbohydrate (GAC) were absent at birth but reached adult frequencies in childhood, concomitant with …

Anti-carbohydrate antibodies (Abs) play crucial roles in pathogen control, but their generation remains poorly understood. Here, we studied how B cell immunity against the Streptococcus pyogenes surface polysaccharide is influenced by age and antigen (Ag) exposure across human blood, spleen, and tonsils. The glycan-targeted response shifted from immunoglobulin M (IgM) biased in children toward Ig…

In the autoimmune disease rheumatoid arthritis, the inflammatory response evolves from protective to pathogenic, causing tissue destruction. Rheumatoid synovitis persists despite the presence of pro-repair SELENOP^hiMerTK⁺CD206⁺ macrophages, suggesting that these cells acquire pro-arthritogenic functions. Patient-derived synovial SELENOP^hiMerTK<sup>+</su…

A deeper understanding of how tissue-localized immune cells arise and function is critical for developing mucosal vaccines. Currently, there are no murine models that specifically target tissue T cells while leaving their lymphoid counterparts untouched. Here, we leverage the observation that during influenza infection, HIF-1α regulatory activity is higher in the lung compared with lymph node CD4…

Plasmodium vivax is the most widespread cause of malaria with a high burden of disease. Progress in reducing the global malaria burden has stalled with no vaccines available partly due to a limited knowledge of targets and mechanisms of protective immunity. We developed a platform to quantify antibody functions to multiple P. vivax antigens and dissect immunity in a longitudinal cohort of childre…