From: Plasmodium falciparum pre-erythrocytic stage vaccine development
Participants | Dose | Efficacy | Refs. |
---|---|---|---|
Vaccines which involve using complete Spz | |||
 Radiation-attenuated Spz PfSPZ (Phase I–II) | |||
  80 adults (18–50 years-old) | Group I (n = 14): 4 doses of 7500 PfSPZ Group II (n = 22): 4 doses of 30,000 PfSPZ Group III (n = 22): 4 doses of 135,000 PfSPZ Group IV (n: 22): 4 or 6 doses of 135,000 PfSPZ | Group I and IV: 0% Group II: 2/16 participants | [6] |
  31 adults (18–45 years-old) | 3 doses of 9.0 × 105 PfSPZ IV every 8 weeks | Homologous challenge: 64% Heterologous challenge: 83% | [23] |
  108 adults (18 to 35 years-old) | Safety cohort: PfSPZ: 1.35 × 105 on day 0 and 2.7 × 105 on day 14 Main cohort: 2.7 × 105 PfSPZ or SSN on days 0, 28, 56, 84 and 140 | 29%. Defining positive blood smears as having at least 2 P. falciparum parasites per 0.5 μl of blood | [24] |
  67 adults (18 to 35 years-old) | Group I (n:3): doses of 3 × 104, 1.35 × 105 and 2.7 × 105 PfSPZ every 4 weeks Group II (n:23): 1.35 × 105 PfSPZ Group III (n:24): 2.7 × 105 PfSPZ (weeks 0, 4, 8, 12 and 20) Group IV (n:6): 2.7 × 105 PfSPZ following the same scheme as for Group III Group V (n = 10): infectivity controls | Homologous CHMI: 4 out of 20 were protected (20%) | [25] |
  67 adults (18 to 45 years-old) | Group I and II (n:30): 2.7 × 105 PfSPZ IV (weeks 0, 4, 8, 12 and 20) Group III (n:15): 4.5 × 105 PfSPZ IV (weeks 0, 8 and 16) Infectivity control (n = 22) | Homologous CHMI Group I and II: 70% Group III: 57% Heterologous CHMI Group I and II: 10% | [27] |
  173 participants (6 months to 45 years-old) | Group I (n:18) Ia: 9 × 105 PfSPZ Ib:1.8 × 106 PfSPZ (weeks 0, 8 and 16) Group II (n:18) IIa: 9 × 105 PfSPZ IIb:1.8 × 106 PfSPZ (weeks 0, 8 and 16) Group III (n:18) IIIa: 9 × 105 PfSPZ IIIb:1.8 × 106 PfSPZ (weeks 0, 8 and 16) Group IV (n:18) IVa: 4.5 × 105 PfSPZ IVb: 9.0 × 106 PfSPZ (weeks 0, 8 and 16) Group V (n:21) Va: 2.7 × 105 (week 0) PfSPZ Vb: 4.5 × 105 PfSPZ Vc: 9 × 105 PfSPZ | NE | [28] |
 Spz administered under drug coverage (Phase I–II) | |||
  PfSPZ-CVac | |||
   40 adults | Group I (n.9) 3 doses of 3.2 × 103 PfSPZ Group II (n.9) 3 doses of 1.28 × 104 PfSPZ Group III (n.9) 3 doses of 5.12 × 104 PfSPZ Placebo (n.13) | Homologous CHMI Group I: 33% Group II: 67% Group III: 100% | [32] |
  CPS-CQ | |||
   15 adults (18–45 years-old) | Group I (n.10) Group control (n.5) Spz administered under chloroquine coverage | Heterologous challenge Group I: 100% | [30] |
  CPS–CQ/CPS-MQ | |||
   20 adults (19–35 years-old) | Group CPS-CQ (n.5) Group CPS-MQ (n.10) Group control (n.5) | Heterologous challenge 60% | [32] |
 Genetically-attenuated Spz vaccines (Phase I–II) | |||
  6 adults (18–42 years-old) | Delivery of Pf p52−/p36− GAP SPZ via infected Anopheles mosquito bite | 83% | [35] |
  10 adults | 150 to 200 bites per subject Pf GAP3KO | 100% | [36] |
Recombinant protein vaccines | |||
 RTS,S (Phase II) | |||
  894 children (5–17 months-old) | 3 doses of RTS,S/AS01E | 56% | [67] |
  180 children (18 months-old to 4 years-old) | 3 doses of RTS,S in 0.5 ml AS01E 3 doses of RTS,S in 0.5 ml AS01E | NE | [72] |
  511 infants (6–10 months) | 3 doses of RTS,S/AS01E | 59.1% | [73] |
  447 children (5–17 months-old) | 3 doses of RTS,S/AS01 | 4.4% | [79] |
 RTS,S (Phase III) | |||
  15,460 children (6 to 12 weeks-old and 5 to 17 months-old) | 3 doses of RTS,S/AS01 | Clinical malaria: 55.1%–Severe malaria: 34.8% | [77] |
  15,460 children (6 to 12 weeks-old and 5 to 17 months-old) | 4 doses of RTS,S/AS01 | (< 50,000 parasites/μl) 5–17 months-old: clinical malaria: 36.3%–severe malaria: 32.2% 6 to 12 weeks-old: clinical malaria: 25.9% Severe malaria: 17.3% 3 years: 0% 5 years-old: 48% and 56% | [78] |
Recombinant viral vectors vaccines | |||
 Chad63 MVA ME-TRAP (Phase I) | |||
  54 adults | Group A (n:28): ChAd63 ME-TRAP increasing the dose from 1 × 108 to 5 × 1010vp ID (groups 1-4) and from 1 × 1010 to 2 × 1011 IM (groups 5–7) Group B (n:26): ChAd63 ME-TRAP, followed at 8 weeks by MVA ME-TRAP and a booster dose for 5 volunteers with ChAd63 ME-TRAP and for 6 volunteers with MVA ME-TRAP | NE | [116] |
  36 adults (18–50 years-old) | Trial A (n:16): ChAd63 ME-TRAP n:6 1 × 1010 VP Trial B (n:30): 105 × 1010 VP a the 56 days MVA ME-TRAP 2 × 108 by intramuscular route (IM) | NE | [111] |
  138 children and infants | Gambia 2–6 year-olds Group 1a (n:6): 1 × 1010 vp ChAd63 ME-TRAP and 1 × 108 pfu MVA ME-TRAP Group 1b (n:6): 1 × 1010 vp ChAd63 ME-TRAP and 2 × 108 pfu MVA ME-TRAP Group 1c (n:6): 1 ml HDCRV Group 1d (n:6): 5 × 010 vp ChAd63 ME-TRAP and 1 × 108 pfu MVA ME-TRAP Group 1e (n:6): 5 × 1010 vp ChAd63 ME-TRAP and 2 × 108 pfu MVA ME-TRAP Group 1f (n:6): 1 ml HDCRV Gambia 5–12 month-olds Group 2a (n:12): 1 × 1010 vp ChAd63 ME-TRAP and 1 × 108 pfu MVA ME-TRAP Group 2b (n:12): 5 × 1010 vp ChAd63 ME-TRAP and 1 × 1010 pfu MVA ME-TRAP Group 2c (n:12): No vaccine Gambia 10 week-olds Group 3a (n:12): 1 × 1010 vp ChAd63 ME-TRAP and 1 × 108 pfu MVA ME-TRAP Group 3b (n:12): 5 × 1010 vp ChAd63 ME-TRAP and 1 × 108 pfu MVA ME-TRAP Group 3c (n:12): No vaccine Burkina Faso (n.30) 5–17 month-olds 5 × 1010 vp ChAd63 ME-TRAP and 1 × 108 pfu MVA ME-TRAP | NE | [110] |
 Chad63 MVA ME-TRAP (Phase II) | |||
  120 adults (18–50 years-old) | n. 120 ChAd63 ME-TRAP (5 × 105 vp) after 8 weeks n. 60 cases: MVA ME-TRAP (2 × 108 pfu) n. 60 controls: anti-rabies vaccine (0.5 ml) | 8% adjusted efficacy: 50% (PCR positivity: more than 10 parasites per μl) | [117] |
  120 adults (18–50 years-old) | n. 120 ChAd63 ME-TRAP (5 × 105 vp) after 8 weeks n. 60 cases: MVA ME-TRAP (2 × 108 pfu) n. 60 controls: anti-rabies vaccine (0.5 ml) | 67% (PCR positivity: more than 10 parasites per μl) | [118] |
 CSVAC (Phase I) | |||
  24 adults (18–50 years-old) | Group 1a (n:4): 5 × 109 vp ChAd63CS Group 1b (n:8): 5 × 109 vp ChAd63CS–day 56 MVA CS 2 × 108 pfu Group 2a (n:4): 5 × 1010 vp ChAd63CS Group 2b (n:8): 5 × 1010 vp ChAd63CS–day 56 MVA CS 2 × 108 pfu | NE | [120] |
  36 adults (18–45 years-old) | Group 1 (n:15): ChAd63 CS 5 × 1010 vp–day 56 MVA CS 2 × 108 UFP–Day 72 CHMI Group 2 (n:15): ChAd63 CS 5 × 1010 vp–day 56 MVA CS 2 × 108 UFP–Day 72 CHMI Group 3 (n:6): Day 72 CHMI | NE | [121] |
 ChAd63/MVA ME-TRAP + Matrix M™ (Phase I) | |||
  23 adults (18 to 50 years-old) | Control group (n:6): ChAd63 ME-TRAP 5 × 1010 vp, day 56 MVA ME-TRAP 2 × 108 pfu Group II (n:9): ChAd63 ME-TRAP 5 × 1010 vp + Matrix-M 25 µg, day 56 MVA ME-TRAP 2 × 108 pfu + Matrix-M 25 µg Group III (n:8): ChAd63 ME-TRAP 5 × 1010 vp + Matrix-M 50 µg, day 56 MVA ME-TRAP 2 × 108 pfu + Matrix-M 50 µg | NE | [123] |