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Normark, J.

Publications and source records attributed to Normark, J..

3 recordsLinked to original sources

Uncovering the genetic diversity of the malaria parasite antigen MSP2 across Sub-Saharan Africa

Genetic diversity in Plasmodium falciparum poses a significant challenge to malaria control and elimination. This is particularly important for developing fully efficacious vaccines, which should include valuable blood stage antigens. Several antigen candidates are highly diverse and require further understanding. We surveyed the genetic diversity of the highly polymorphic merozoite surface protein 2 (MSP2) in 2761 P. falciparum isolates collected across Sub-Saharan Africa. Using PCR-based genotyping and long-read sequencing, we identified extensive diversity among msp2 size variants and sequences. Some size variants were more prevalent than others across different geographical regions, transmission intensities, and time points. These variants comprised multiple unique sequences, of which several were geographically and temporally widespread. Our study reveals greater msp2 sequence diversity than previously known, while also identifying interesting similarities in sequence and gene length across Sub-Saharan Africa. These findings support the further exploration of common msp2 variants in relation to parasite virulence and vaccine development.

microbiology↗

Scalable single-cell metagenomic analysis with Bascet and Zorn

Single-cell metagenomic sequencing (scMetaG) can provide maximum-resolution insights into complex microbial communities. However, existing bioinformatic tools are not equipped to handle the massive amounts of data generated by novel high-throughput scMetaG methods. Here, we present a bioinformatic toolkit for complete, end-to-end scMetaG analysis: (i) Bascet, a command-line suite designed to scale to massive scMetaG datasets ([≥]1 million cells); (ii) Zorn, an R package/workflow manager that enables reproducible scMetaG data analysis, exploration, and visualization (http://zorn.henlab.org/). Enabled by recent advances in droplet microfluidics, we use Bascet and Zorn to develop and optimize a high-throughput scMetaG method on a ten-species mock community. To showcase their utility on a real-world sample, we use Bascet and Zorn to characterize a human saliva sample, generating single-amplified genomes (SAGs) from >10k prokaryotic cells. Overall, Bascet and Zorn enable reproducible scMetaG analysis, allowing users to query microbiomes at unprecedented resolution and scale.

microbiology↗

Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection

Understanding immune responses following SARS-CoV-2 breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses following Omicron/BA.1 infection in mRNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation (SHM) and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells (MBCs). BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit toward the receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 variants of concern (VOCs). Together, these findings provide fundamental insights into the role of pre-existing immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure. One sentence summaryBA.1 breakthrough infection activates pre-existing memory B cells with broad activity against SARS-CoV-2 variants.

immunology↗