TY - JOUR
T1 - Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults
T2 - Safety, Immunogenicity, and Efficacy
AU - Bennett, Jason W.
AU - Yadava, Anjali
AU - Tosh, Donna
AU - Sattabongkot, Jetsumon
AU - Komisar, Jack
AU - Ware, Lisa A.
AU - McCarthy, William F.
AU - Cowden, Jessica J.
AU - Regules, Jason
AU - Spring, Michele D.
AU - Paolino, Kristopher
AU - Hartzell, Joshua D.
AU - Cummings, James F.
AU - Richie, Thomas L.
AU - Lumsden, Joanne
AU - Kamau, Edwin
AU - Murphy, Jittawadee
AU - Lee, Cynthia
AU - Parekh, Falgunee
AU - Birkett, Ashley
AU - Cohen, Joe
AU - Ballou, W. Ripley
AU - Polhemus, Mark E.
AU - Vanloubbeeck, Yannick F.
AU - Vekemans, Johan
AU - Ockenhouse, Christian F.
N1 - Publisher Copyright:
© 2016 Castro-Sesquen et al.
PY - 2016/2/26
Y1 - 2016/2/26
N2 - Background: 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. Methods: 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 15μg, 30μg, or 60μg respectively of VMP001, all formulated in 500μL 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. Results: 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. Significance: 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.
AB - Background: 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. Methods: 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 15μg, 30μg, or 60μg respectively of VMP001, all formulated in 500μL 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. Results: 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. Significance: 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.
UR - http://www.scopus.com/inward/record.url?scp=84959269051&partnerID=8YFLogxK
U2 - 10.1371/journal.pntd.0004423
DO - 10.1371/journal.pntd.0004423
M3 - Article
C2 - 26919472
AN - SCOPUS:84959269051
SN - 1935-2727
VL - 10
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 2
M1 - e0004423
ER -