Biology subjects

Plaza, D. F.

Publications and source records attributed to Plaza, D. F..

3 recordsLinked to original sources

bioRxiv2025

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↗

bioRxiv2024

Naturally acquired IgG responses to Plasmodium falciparum do not target the conserved termini of the malaria vaccine candidate merozoite surface protein 2

Malaria remains a significant burden, and a fully protective vaccine against Plasmodium falciparum is critical for reducing morbidity and mortality. Antibody responses against the blood-stage antigen merozoite surface protein 2 (MSP2) are associated with protection from P. falciparum malaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. New tools, such as long-read sequencing and accurate protein structure modelling allow us to more easily study the genetic diversity and immune responses towards antigens from clinical isolates. This study sought to better understand naturally acquired MSP2-specific antibody responses. IgG responses against recombinantly expressed full- length, central polymorphic regions, and peptides derived from the conserved termini of MSP2 variants sequenced from patient isolates, were tested in plasma from travelers with recent, acute malaria and from individuals living in an endemic area of Tanzania. IgG responses towards full MSP2 and truncated MSP2 antigens were variant specific. IgG antibodies in the plasma of first-time infected or previously exposed travelers did not recognize the conserved termini of expressed MSP2 variants by ELISA, but they bound 13- amino acid long linear epitopes from the termini in a custom-made peptide array. Alphafold3 modelling suggests extensive structural heterogeneity in the conserved termini upon antigen oligomerization. IgG from individuals living in an endemic region, many who were asymptomatically infected, did not recognize the conserved termini by ELISA. Our results suggest that responses to the variable regions are important for the development of naturally acquired immunity towards MSP2.

immunology↗

bioRxiv2022

A genomic platform for surveillance and antigen discovery in Plasmodium spp. using long-read amplicon sequencing

Many vaccine candidate proteins are under strong selective pressure to diversify in terms of antigenicity. We present a sequencing and data analysis platform for epidemiological surveillance and discovery of indel-rich vaccine antigens by long-read circular consensus sequencing (CCS) in multiclonal pathogen isolates. Our platform uses 40 PCR primers to asymmetrically barcode and identify multiclonal infections in pools of up to 384 samples. We validated the method using 235 mock infections combining 10 synthetic variants of the indel-rich gene merozoite surface protein 2 of Plasmodium falciparum at different concentrations and infection complexities, as well as 95 isolates from P. falciparum-infected residents of Nyamisati, Tanzania. We also constructed a fully automated analysis pipeline that streamlines the processing and interpretation of epidemiological and antigenic diversity data from demultiplexed FASTQ files. This platform can be easily adapted to other polymorphic antigens of interest in Plasmodium and other human pathogens.

genomics↗