22 research outputs found
Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies
BACKGROUND. Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite’s Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vaccination.
METHODS. Safety and immunogenicity of replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and modified vaccinia virus Ankara (MVA) viral vectored vaccines targeting PvDBP_RII (Salvador I strain) were assessed in an open-label dose-escalation phase Ia study in 24 healthy UK adults. Vaccines were delivered by the intramuscular route in a ChAd63-MVA heterologous prime-boost regimen using an 8-week interval.
RESULTS. Both vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. PvDBP_RII–specific ex-vivo IFN-γ T cell, antibody-secreting cell, memory B cell, and serum IgG responses were observed after the MVA boost immunization. Vaccine-induced antibodies inhibited the binding of vaccine homologous and heterologous variants of recombinant PvDBP_RII to the DARC receptor, with median 50% binding-inhibition titers greater than 1:100.
CONCLUSION. We have demonstrated for the first time to our knowledge that strain-transcending antibodies can be induced against the PvDBP_RII antigen by vaccination in humans. These vaccine candidates warrant further clinical evaluation of efficacy against the blood-stage P. vivax parasite
PMD49 MECHANICAL COMPLICATIONS ASSOCIATED WITH INTRAMEDULLARY NAILING FOR TROCHANTERIC, INTERTROCHANTERIC AND SUBTROCHANTERIC FEMUR FRACTURES
PMD47 BREAKAGE OF INTRAMEDULLARY NAILING IN TROCHANTERIC, INTERTROCHANTERIC AND SUBTROCHANTERIC FEMUR FRACTURES
PSU32 INTRAMEDULLARY NAILING OF TIBIAL FRACTURES: PATIENT CHARACTERISTICS ASSOCIATED WITH POSTOPERATIVE COMPLICATIONS
PSU23 INTRAMEDULLARY NAILING OF FEMORAL FRACTURES: PATIENT CHARACTERISTICS ASSOCIATED WITH POSTOPERATIVE COMPLICATIONS
MT1 LONG BONE FRACTURES: OVERVIEW OF SURGICAL APPROACHES BY FRACTURE TYPES AND PATIENT PROFILE
PIT4 PATIENT CHARACTERISTICS AND HEALTHCARE UTILIZATION FOLLOWING COMMINUTED GUSTILO-ANDERSON TYPE III FRACTURES
PIT14 COSTS AND HEALTHCARE UTILIZATION OF TRAUMA CASES WITH COMMINUTED GUSTILO-ANDERSON TYPE III FRACTURES
Preclinical assessment of viral vectored and protein vaccines targeting the Duffy-binding protein region II of Plasmodium vivax
10.3389/fimmu.2015.00348Frontiers in Immunology6JUN34