PvDBPII / University of Oxford - LARVOL DELTA

Atypical memory B cells from natural malaria infection produced broadly neutralizing antibodies against Plasmodium vivax variants. (PubMed, PLoS Pathog) - "Here, P. vivax Duffy Binding Protein II (PvDBPII) probes were generated to detect the development and durability of specific aMBCs, and to demonstrate the capacity of these cells to produce neutralizing antibodies following natural infections...Together, our findings revealed that P. vivax infections elicited the development and persistence of P. vivax-specific aMBCs. The accumulation of aMBCs during and following infections might play an important role in producing protective antibodies against malaria."

Journal • Infectious Disease • Malaria • IGH

Molecular epidemiology and genetic diversity of disappearing Plasmodium vivax in southern Thailand. (PubMed, Sci Rep) - "In Yala, polyclonal infections were found in 53.7% of pvdbpII and 47.8% of pvmsp142 isolates, with average COI of 1.6 and 1.7. Both genes were under balancing selection. Distinct genetic differences were found between Yala and Tak in pvmsp142, providing a local genotypic profile useful for tracing parasite origins."

Journal • Infectious Disease • Malaria

Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1 (clinicaltrials.gov) - P1/2 | N=24 | Completed | Sponsor: University of Oxford | Recruiting ➔ Completed

Trial completion • Infectious Disease • Malaria

Characterizing human monoclonal antibodies induced by vaccines against Plasmodium vivax Duffy-binding protein (ASTMH 2024) - "Data from this large panel of anti-PvDBPII mAb will be used to define characteristics that determine the functional potency of mAb across different epitopes within PvDBPII. This will help guide the rational redesign of new PvDBPII-based vaccines to improve on efficacy as well as development of prophylactic mAb against blood-stage P. vivax ."

Infectious Disease • Malaria

Genetic diversity of Plasmodium vivax Duffy Binding Protein in Ethiopia and comparison with other geographical isolates (ASTMH 2024) - "PvDBPII of the Ethiopian P. vivax isolates showed low nucleotide but high haplotype diversity. Among the Ethiopian P. vivax isolates, almost half of the sequences were identical to the Sal-I reference sequence. However, there were unique haplotypes observed in the Ethiopian isolates, which does not share with isolates from other geographical areas."

Infectious Disease • Malaria

Polarization toward Tfh2 cell involved in development of MBC and antibody responses against Plasmodium vivax infection. (PubMed, PLoS Negl Trop Dis) - "Present study demonstrated that P. vivax infection induced cTfh polarization into cTfh2 subset, and alteration of memory cTfh2 phenotype from CM to EM phase. These P. vivax-induced cTfh responses significantly associated with generation of MBCs and antibody responses. Therefore, cTfh2 cells might possibly influence humoral immunity by inducing expansion of activated and atypical MBCs, and by generating P. vivax-specific MBCs and antibody responses following natural infection."

Journal • Infectious Disease • Malaria • CEBPZ

Genetic polymorphism of Duffy binding protein in Pakistan Plasmodium vivax isolates. (PubMed, Acta Trop) - "The findings are crucial for understanding the genetic characteristics of Pakistan PvDBPII. A comprehensive analysis of nucleotide diversity and evolutionary trends in the global PvDBPII population offers valuable insights for the development of vivax malaria vaccines based on this antigen."

Journal • Infectious Disease • Malaria

Evaluation of the precision of the Plasmodium knowlesi growth inhibition assay for Plasmodium vivax Duffy-binding protein-based malaria vaccine development. (PubMed, Vaccine) - "Moreover, the ninety-five percent confidence interval (95 %CI) for %GIA or GIA50 in repeat assays was calculated in this investigation. The error range determined in this study will help researchers to compare PkGIA results from different assays and studies appropriately, thus supporting the development of future blood-stage malaria vaccine candidates, specifically second-generation PvDBPII-based formulations."

Journal • Infectious Disease • Malaria

Genetic differentiation of Plasmodium vivax duffy binding protein in Ethiopia and comparison with other geographical isolates. (PubMed, Malar J) - "PvDBPII of the Ethiopian P. vivax isolates showed low nucleotide but high haplotype diversity, this pattern of genetic variability suggests that the population may have undergone a recent expansion. Among the Ethiopian P. vivax isolates, almost half of the sequences were identical to the Sal-I reference sequence. However, there were unique haplotypes observed in the Ethiopian isolates, which does not share with isolates from other geographical areas. There were two haplotypes that were common among populations across the globe. Categorizing population haplotype frequency can help to determine common haplotypes for designing an effective blood-stage vaccine which will have a significant role for the control and elimination of P. vivax."

Journal • Infectious Disease • Malaria

Analyses of human vaccine-specific circulating and bone marrow-resident B cell populations reveal benefit of delayed vaccine booster dosing with blood-stage malaria antigens. (PubMed, Front Immunol) - "We have previously reported primary endpoints of a clinical trial testing two vaccine platforms for the delivery of Plasmodium vivax malaria DBPRII: viral vectors (ChAd63, MVA), and protein/adjuvant (PvDBPII with 50µg Matrix-M™ adjuvant)...In contrast, the CD4+ and CD8+ T cell responses were impacted by vaccine platform but not dosing regimen and did not correlate with in vivo growth inhibition in a challenge model. Taken together, our DBPRII and RH5 data suggest an opportunity for protein/adjuvant dosing regimen optimisation in the context of rational vaccine development against pathogens where protection is antibody-mediated."

Journal • Infectious Disease • Malaria • CD4 • CD8

PvDBPII elicits multiple antibody-mediated mechanisms that reduce growth in a Plasmodium vivax challenge trial. (PubMed, NPJ Vaccines) - "These data suggest that multiple immune mechanisms elicited by PvDBPII immunization are likely to be associated with protection and the immune correlates identified could guide the development of an effective vaccine for P. vivax malaria. Importantly, all the polyfunctional antibody features that correlated with protection cross-reacted with both PvDBPII SalI and PvW1 variants, suggesting that immunization with PvDBPII should protect against diverse P. vivax isolates."

Journal • Infectious Disease • Malaria • C1Q

Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans. (PubMed, Sci Rep) - "Furthermore, the anti-PvDBPII antibodies were able to block the interaction of DARC with the homologous PvDBPII SalI allele as well as the heterologous PvDBPII PvW1 allele from a Thai clinical isolate that is used for controlled human malaria infections (CHMI). The cross-reactivity of these antibodies with PvW1 suggest that immunization with the PvDBPII SalI strain should neutralize reticulocyte invasion by the challenge P. vivax strain PvW1."

Journal • CNS Disorders • Infectious Disease • Malaria • Psychiatry • Schizophrenia

Genetic diversity and natural selection of Plasmodium vivax reticulocyte invasion genes in Ecuador. (PubMed, Malar J) - "pvdbpII and pvama1 genetic diversity found in Ecuadorian P. vivax was very similar to that encountered in other malaria endemic countries with varying transmission levels and segregated by geographic region. The highest diversity of P. vivax invasion genes in Ecuador was found in the Amazonian region. Although selection appeared to have small effect on pvdbpII and pvrbp1a-2, pvama1 was influenced by significant balancing selection."

Journal • Infectious Disease • Malaria

Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection. (PubMed, Sci Transl Med) - "Both viral-vectored and protein vaccines were well tolerated and elicited expected, short-lived adverse events. Together, these results support further clinical evaluation of the PvDBPII/Matrix-M P. vivax vaccine."

Journal • Infectious Disease • Malaria

Characterization of Duffy Binding Protein II-specific CD4T cell responses in Plasmodium vivax patients. (PubMed, Sci Rep) - "Altogether, PvDBPII-specific CD4T cells were developed in natural P. vivax infections. Data on their antigenicity could facilitate development of an efficacious vivax malaria vaccine."

Journal • Infectious Disease • Malaria • IFNG • TNFA

Acquisition of antibodies to Plasmodium falciparum and Plasmodium vivax antigens in pregnant women living in a low malaria transmission area of Brazil. (PubMed, Malar J) - "Pregnant Brazilian women had low levels of antibodies to pregnancy-specific VSAs that increased with exposure. They frequently recognized both VAR2CSA DBL domains and P. vivax antigens, but only the latter varied with infection. Apparent antibody prevalence is highly dependent on the assay platform used."

Journal • Infectious Disease • Malaria

WITHDRAWN Validation of in silico predicted P. vivax Duffy Binding protein MHC class II restricted peptides (ASTMH 2022) - "Definition of the epitopes that are recognized by T cells to the P. vivax Duffy Binding protein (PvDBPII) is critical to understanding T cell responses in natural immunity for developing an effective vaccine...A peptide pool adjuvanted in GLA-SE was performed to study the correlation between the immunogenicity and the peptide - MHC class II binding assay. Determining the functional role of the Tfh cells to provide help to B cells will be critical to design an ideal vaccine candidate for PvDBP that can generate a long-lasting, broadly neutralizing, antibody response."

Late-breaking abstract • HLA-DRB1

Evaluating functional activity of human monoclonal antibodies to Plasmodium vivax Duffy Binding protein using the Plasmodium knowlesi transgenic model expressing PvDBP (ASTMH 2022) - "Lastly, preliminary combinatorial experiments testing two mAbs at once indicate potential synergistic effects of humAbs on growth inhibition. This PkPvDBP transgenic model will allow evaluation of strain variation of PvDBPII and pvdbp gene amplification on humAb efficacy and can identify optimal combinations of humAbs for future adoptive transfer studies in non-human primate models and humans."

Infectious Disease • Malaria

Plasmodium vivax Duffy Binding Protein-Based Vaccine: a Distant Dream. (PubMed, Front Cell Infect Microbiol) - "Despite its highly polymorphic nature, the amino-terminal cysteine-rich region II of PvDBP (PvDBPII) has been considered as an attractive target for vaccine-mediated immunity and has successfully completed the clinical trial Phase 1...As a result, there is an urgent need to assess and re-assess various caveats connected to PvDBP, which might help in designing a long-term promising vaccine for P. vivax malaria. This review mainly deals with a bunch of rising concerns for validation of DBPII as a vaccine candidate antigen for P. vivax malaria."

Journal • Review • Infectious Disease • Malaria

Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1 (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: University of Oxford | Trial completion date: Feb 2022 ➔ Aug 2022 | Trial primary completion date: Feb 2022 ➔ Aug 2022

Trial completion date • Trial primary completion date • Infectious Disease • Malaria

Sequence analysis of Plasmodium vivax Duffy binding proteins reveals the presence of unique haplotypes and diversifying selection in Ethiopian isolates. (PubMed, Malar J) - "The results of this study are concurrent with the multivalent vaccine approach to design an effective treatment. However, the presence of novel haplotypes in Ethiopian isolates that were not shared by other global sequences warrant further investigation."

Journal • Infectious Disease

Profiling Humoral Immune Response Against Pre-Erythrocytic and Erythrocytic Antigens of Malaria Parasites Among Neotropical Primates in the Brazilian Atlantic Forest. (PubMed, Front Cell Infect Microbiol) - "Antibodies against erythrocytic recombinant antigens of P. vivax, Apical membrane antigen 1 (PvAMA-1), Erythrocyte binding protein 2 (PvEBP-2) and domain II of Duffy binding protein (PvDBPII) were also evaluated...These findings showed a high prevalence of naturally acquired antibodies against CSP repeats in all studied areas, suggesting an intense exposure to infected-mosquitoes bites of NP from all families. However, mainly monkeys of Atelidae family showed antibodies against P. vivax erythrocytic antigens, suggesting blood infection, which might serve as potential reservoirs of malaria in the Atlantic Forest."

Journal • Infectious Disease • Malaria

Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1 (clinicaltrials.gov) - P1/2; N=24; Recruiting; Sponsor: University of Oxford; N=17 ➔ 24; Trial completion date: Jun 2022 ➔ Feb 2022; Trial primary completion date: Jun 2022 ➔ Feb 2022

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Infectious Disease • Malaria

Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1 (clinicaltrials.gov) - P1/2; N=17; Recruiting; Sponsor: University of Oxford; Trial completion date: Nov 2021 ➔ Jun 2022; Trial primary completion date: Nov 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Malaria