Controlled human malaria infection of healthy adults with lifelong malaria exposure to assess safety, immunogenicity, and efficacy of the asexual blood stage malaria vaccine candidate GMZ2
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Controlled human malaria infection of healthy adults with lifelong malaria exposure to assess safety, immunogenicity, and efficacy of the asexual blood stage malaria vaccine candidate GMZ2. / Dejon-Agobe, Jean Claude; Ateba-Ngoa, Ulysse; Lalremruata, Albert; Homoet, Andreas; Engelhorn, Julie; Nouatin, Odilon Paterne; Edoa, Jean Ronald; Fernandes, José F; Esen, Meral; Mouwenda, Yoanne Darelle; Betouke Ongwe, Eunice M; Massinga-Loembe, Marguerite; Hoffman, Stephen L; Sim, B Kim Lee; Theisen, Michael; Kremsner, Peter G; Adegnika, Ayôla A; Lell, Bertrand; Mordmüller, Benjamin.
In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 69, No. 8, 2019, p. 1377-1384.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Controlled human malaria infection of healthy adults with lifelong malaria exposure to assess safety, immunogenicity, and efficacy of the asexual blood stage malaria vaccine candidate GMZ2
AU - Dejon-Agobe, Jean Claude
AU - Ateba-Ngoa, Ulysse
AU - Lalremruata, Albert
AU - Homoet, Andreas
AU - Engelhorn, Julie
AU - Nouatin, Odilon Paterne
AU - Edoa, Jean Ronald
AU - Fernandes, José F
AU - Esen, Meral
AU - Mouwenda, Yoanne Darelle
AU - Betouke Ongwe, Eunice M
AU - Massinga-Loembe, Marguerite
AU - Hoffman, Stephen L
AU - Sim, B Kim Lee
AU - Theisen, Michael
AU - Kremsner, Peter G
AU - Adegnika, Ayôla A
AU - Lell, Bertrand
AU - Mordmüller, Benjamin
PY - 2019
Y1 - 2019
N2 - BACKGROUND: GMZ2 is a recombinant malaria vaccine inducing immune responses against Plasmodium falciparum (Pf) merozoite surface protein-3 and glutamate-rich protein. We used standardized controlled human malaria infection (CHMI) to assess the efficacy of this asexual blood-stage vaccine.METHODS: We vaccinated 50 healthy, adult volunteers with lifelong exposure to Pf 3 times, at 4-week intervals, with 30 or 100 µg GMZ2 formulated in CAF01, a liposome-based adjuvant; 100 µg GMZ2, formulated in Alhydrogel; or a control vaccine (Verorab). Approximately 13 weeks after the last vaccination, 35/50 volunteers underwent CHMI by direct venous inoculation of 3200 Pf sporozoites (Sanaria® PfSPZ Challenge).RESULTS: Adverse events were similarly distributed between GMZ2 and control vaccinees. Baseline-corrected anti-GMZ2 antibody concentrations 4 weeks after the last vaccination were higher in all 3 GMZ2-vaccinated arms, compared to the control group. All GMZ2 formulations induced similar antibody levels. CHMI resulted in 29/34 (85%) volunteers with Pf parasitemia and 15/34 (44%) with malaria (parasitemia and symptoms). The proportion of participants with malaria (2/5 control, 6/10 GMZ2-Alhydrogel, 2/8 30 µg GMZ2-CAF01, and 5/11 100 µg GMZ2-CAF01) and the time it took them to develop malaria were similar in all groups. Baseline, vaccine-specific antibody concentrations were associated with protection against malaria.CONCLUSIONS: GMZ2 is well tolerated and immunogenic in lifelong-Pf-exposed adults from Gabon, with similar antibody responses regardless of formulation. CHMI showed no protective effect of prior vaccination with GMZ2, although baseline, vaccine-specific antibody concentrations were associated with protection. CHMI with the PfSPZ Challenge is a potent new tool to validate asexual, blood-stage malaria vaccines in Africa.CLINICAL TRIALS REGISTRATION: Pan-African Clinical Trials: PACTR201503001038304.
AB - BACKGROUND: GMZ2 is a recombinant malaria vaccine inducing immune responses against Plasmodium falciparum (Pf) merozoite surface protein-3 and glutamate-rich protein. We used standardized controlled human malaria infection (CHMI) to assess the efficacy of this asexual blood-stage vaccine.METHODS: We vaccinated 50 healthy, adult volunteers with lifelong exposure to Pf 3 times, at 4-week intervals, with 30 or 100 µg GMZ2 formulated in CAF01, a liposome-based adjuvant; 100 µg GMZ2, formulated in Alhydrogel; or a control vaccine (Verorab). Approximately 13 weeks after the last vaccination, 35/50 volunteers underwent CHMI by direct venous inoculation of 3200 Pf sporozoites (Sanaria® PfSPZ Challenge).RESULTS: Adverse events were similarly distributed between GMZ2 and control vaccinees. Baseline-corrected anti-GMZ2 antibody concentrations 4 weeks after the last vaccination were higher in all 3 GMZ2-vaccinated arms, compared to the control group. All GMZ2 formulations induced similar antibody levels. CHMI resulted in 29/34 (85%) volunteers with Pf parasitemia and 15/34 (44%) with malaria (parasitemia and symptoms). The proportion of participants with malaria (2/5 control, 6/10 GMZ2-Alhydrogel, 2/8 30 µg GMZ2-CAF01, and 5/11 100 µg GMZ2-CAF01) and the time it took them to develop malaria were similar in all groups. Baseline, vaccine-specific antibody concentrations were associated with protection against malaria.CONCLUSIONS: GMZ2 is well tolerated and immunogenic in lifelong-Pf-exposed adults from Gabon, with similar antibody responses regardless of formulation. CHMI showed no protective effect of prior vaccination with GMZ2, although baseline, vaccine-specific antibody concentrations were associated with protection. CHMI with the PfSPZ Challenge is a potent new tool to validate asexual, blood-stage malaria vaccines in Africa.CLINICAL TRIALS REGISTRATION: Pan-African Clinical Trials: PACTR201503001038304.
U2 - 10.1093/cid/ciy1087
DO - 10.1093/cid/ciy1087
M3 - Journal article
C2 - 30561539
VL - 69
SP - 1377
EP - 1384
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 8
ER -
ID: 227986651