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Table 1 Clinical phases for developing vaccines against sporozoite stage malaria

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]

  1. vp viral particles, pfu plaque-forming units, HDCRV human diploid cell inactivated anti-rabies vaccine, SSN normal saline solution, NE not evaluated