Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.
A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy-...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-02-01
|
Series: | PLoS Neglected Tropical Diseases |
Online Access: | http://europepmc.org/articles/PMC4769081?pdf=render |
id |
doaj-1d1246902c114fc3828a7b9030188e30 |
---|---|
record_format |
Article |
spelling |
doaj-1d1246902c114fc3828a7b9030188e302020-11-24T20:45:00ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352016-02-01102e000442310.1371/journal.pntd.0004423Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.Jason W BennettAnjali YadavaDonna ToshJetsumon SattabongkotJack KomisarLisa A WareWilliam F McCarthyJessica J CowdenJason RegulesMichele D SpringKristopher PaolinoJoshua D HartzellJames F CummingsThomas L RichieJoanne LumsdenEdwin KamauJittawadee MurphyCynthia LeeFalgunee ParekhAshley BirkettJoe CohenW Ripley BallouMark E PolhemusYannick F VanloubbeeckJohan VekemansChristian F OckenhouseA vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.http://europepmc.org/articles/PMC4769081?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jason W Bennett Anjali Yadava Donna Tosh Jetsumon Sattabongkot Jack Komisar Lisa A Ware William F McCarthy Jessica J Cowden Jason Regules Michele D Spring Kristopher Paolino Joshua D Hartzell James F Cummings Thomas L Richie Joanne Lumsden Edwin Kamau Jittawadee Murphy Cynthia Lee Falgunee Parekh Ashley Birkett Joe Cohen W Ripley Ballou Mark E Polhemus Yannick F Vanloubbeeck Johan Vekemans Christian F Ockenhouse |
spellingShingle |
Jason W Bennett Anjali Yadava Donna Tosh Jetsumon Sattabongkot Jack Komisar Lisa A Ware William F McCarthy Jessica J Cowden Jason Regules Michele D Spring Kristopher Paolino Joshua D Hartzell James F Cummings Thomas L Richie Joanne Lumsden Edwin Kamau Jittawadee Murphy Cynthia Lee Falgunee Parekh Ashley Birkett Joe Cohen W Ripley Ballou Mark E Polhemus Yannick F Vanloubbeeck Johan Vekemans Christian F Ockenhouse Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy. PLoS Neglected Tropical Diseases |
author_facet |
Jason W Bennett Anjali Yadava Donna Tosh Jetsumon Sattabongkot Jack Komisar Lisa A Ware William F McCarthy Jessica J Cowden Jason Regules Michele D Spring Kristopher Paolino Joshua D Hartzell James F Cummings Thomas L Richie Joanne Lumsden Edwin Kamau Jittawadee Murphy Cynthia Lee Falgunee Parekh Ashley Birkett Joe Cohen W Ripley Ballou Mark E Polhemus Yannick F Vanloubbeeck Johan Vekemans Christian F Ockenhouse |
author_sort |
Jason W Bennett |
title |
Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy. |
title_short |
Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy. |
title_full |
Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy. |
title_fullStr |
Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy. |
title_full_unstemmed |
Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy. |
title_sort |
phase 1/2a trial of plasmodium vivax malaria vaccine candidate vmp001/as01b in malaria-naive adults: safety, immunogenicity, and efficacy. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2016-02-01 |
description |
A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials. |
url |
http://europepmc.org/articles/PMC4769081?pdf=render |
work_keys_str_mv |
AT jasonwbennett phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT anjaliyadava phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT donnatosh phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT jetsumonsattabongkot phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT jackkomisar phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT lisaaware phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT williamfmccarthy phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT jessicajcowden phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT jasonregules phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT micheledspring phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT kristopherpaolino phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT joshuadhartzell phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT jamesfcummings phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT thomaslrichie phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT joannelumsden phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT edwinkamau phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT jittawadeemurphy phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT cynthialee phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT falguneeparekh phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT ashleybirkett phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT joecohen phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT wripleyballou phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT markepolhemus phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT yannickfvanloubbeeck phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT johanvekemans phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy AT christianfockenhouse phase12atrialofplasmodiumvivaxmalariavaccinecandidatevmp001as01binmalarianaiveadultssafetyimmunogenicityandefficacy |
_version_ |
1716815866256949248 |