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Table 1 Clinical phases for developing vaccines against sporozoite stage malaria

From: Plasmodium falciparum pre-erythrocytic stage vaccine development

ParticipantsDoseEfficacyRefs.
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 weeksHomologous 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 adultsGroup 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 bite83%[35]
  10 adults150 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/AS01E56%[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/AS014.4%[79]
 RTS,S (Phase III)
  15,460 children (6 to 12 weeks-old and 5 to 17 months-old)3 doses of RTS,S/AS01Clinical 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 adultsGroup 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 infantsGambia 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]
  1. vp viral particles, pfu plaque-forming units, HDCRV human diploid cell inactivated anti-rabies vaccine, SSN normal saline solution, NE not evaluated