TABLE 1.
Current clinical trials for Plasmodium falciparum erythrocyte stage vaccine candidates.
| Vaccine formulation | Trial characteristics | Main results | References | |
|
Chemically synthesized vaccine MSP3-LSP Adjuvants: Montanide ISA 720 and aluminum hydroxide |
Phase Ia |
Doses evaluated: 10, 30, 100, and 300 μg of MSP3-LSP (days 0, 30, and 120) Administration route: Subcutaneous Participants: 36 (18–45 years old) Year: 2003–2004 |
– formulation with Al(OH)3 was better tolerated – cytophilic IgG1 subclass humoral response predominated |
Audran et al., 2005; Sirima et al., 2009 |
| Phase Ib |
Dose: 30 μg of MSP3-LSP (days 0, 28, and 112) Participants: Group 1: 30 (18–45 years old); Group 2: 55 (12–24 months old) Year: 2007–2008 |
– vaccine was safe and well tolerated – absence of immune humoral response in the vaccinated group |
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|
Chemically synthesized vaccine P27A Adjuvants: GLA-SE/alhydrogel |
Phase Ia |
Dose: 10 and 50 μg of P27A (days 0, 28, and 56) Administration route: Intramuscular Participants: 16 adults Year: 2014–2015 |
– high frequency of local and systemic adverse events (AE) | Steiner-Monard et al., 2018 |
| Phase Ib |
Dose: 10 and 50 μg of P27A (days 0, 28, and 56) Administration route: Intramuscular Participants: 40 adults Year: 2014–2015 |
– > humoral immune response in individuals who had not been exposed to malaria – low antibody dependent (ADCI) – anti-P27A cell inhibition capability (in vitro trials) |
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|
Recombinant vaccine BK-SE36 Adjuvant: aluminum hydroxide Expression system (ES): Escherichia coli |
Phase Ia |
Dose evaluated: 50 and 100 μg of SE36 (days 0, 21, and 42) Administration route: Subcutaneous Participants: 40 adults Year: 2008 |
– 100% seroconversion (29/29 participants) at the end of follow-up (day 63) | Horii et al., 2010; Palacpac et al., 2013 |
| Phase Ib |
Dose: 50 and 100 μg of SE36 (days 0 and 21) Participants: Stage 1: 56 (21–40 years old)/Stage 2: 84 (6–20 months old) Year: 2010–2011 |
– significant increase in Ab titers only in 6- to 10-year-old participants (5/71-fold) | ||
|
Recombinant vaccine AMA-1 DiCo Adjuvants: aluminum hydroxide, GLA-SE ES: Pichia pastoris |
Phase Ia |
Dose evaluated: 50 μg of AMA-1 DiCo (days 0, 28, and 182) Administration route: Intramuscular Participants: 30 (20–25 years old) Year: 2014–2015 |
– average IgG concentration: adjuvant GLA-SE (37.7–60.2 mg/ml) – alhydrogel (19–22.9 mg/ml) |
Sirima et al., 2017 |
| Phase Ib |
Dose evaluated: 50 μg of AMA-1 DiCo (days 0, 28, and 182) Participants: 36 (20–25 years old) Year: 2014–2015 |
– significant increase in IgG (90–150 mg/ml) during week 30 in the GLA-SE group | ||
|
Recombinant vaccine PRIMVAC Adjuvants: alhydrogel and GLA-SE ES: E. coli |
Phase Ia/Ib |
Dose evaluated: 20, 50, and 100 μg of PRIMVAC (days 0, 28, and 56) Administration route: Intramuscular Participants: 68 (18–35 years old) Year: 2016–2018 |
– not published | (Chêne et al., 2016; Sirima et al., 2016a) |
|
Recombinant vaccine PAMVAC Adjuvants: alhydrogel and GLA-SE ES: Drosophila melanogaster |
Phase Ia/Ib |
Dose evaluated: 20, 50, and 100 μg of PRIMVAC (days 0, 28, and 56) Administration route: Intramuscular Participants: 66 (18–35 years old) Year: 2016–2017 |
– not published | (Chêne et al., 2016) |
|
Recombinant vaccine PfPEBS Adjuvants: aluminum hydroxide ES: E. coli |
Phase Ia/Ib |
Dose evaluated: 5 or 30 μg of PfPEBS (days 0 and 28) Administration route: Subcutaneous Participants: 36 (18–45 years old) |
– not published | Druilhe and Genton, 2012 |
|
Recombinant vaccine EBA-175 RII NG Adjuvant: aluminum phosphate ES: P. pastoris |
Phase Ia |
Dose: 5, 20, 80, and 160 μg of EBA-175 (days 0, 42, and 194) Administration route: Intramuscular Participants: 80 adults Year: 2008 |
– vaccine well tolerated – > Ab titers following third immunization; however, becoming reduced at the end of follow-up |
El Sahly et al., 2010 |
| Phase Ib |
Dose: 5, 20, and 80 μg of EBA-175 (days 0, 42, and 194) Administration route: Intramuscular Participants: 60 adults Year: 2010–2012 |
– inhibition of parasite growth in vitro: 25.0% in the placebo group and 12.0–20.0% in the vaccinated group | Koram et al., 2016 | |
|
Recombinant vaccine GMZ2 Adjuvant: alhydrogel Expression system: Lactococcus lactis |
Phase Ia |
Dose: 10, 30, or 100 μg of GMZ2 (days 0, 28, and 56) Administration route: subcutaneous Participants: 30 adults Year: 2006–2007 |
– high frequency of local and systemic adverse reactions (grades 1 and 2) | Esen et al., 2009 |
| Phase Ib |
Dose: 100 μg of GMZ2 (days 0, 28, and 56) Participants: 40 adults (18–45 years old) Year: 2007–2008 |
– greater amount of anti-GMZ2 Ab titers in the experimental group (>1.4-fold) | Mordmüller et al., 2010 | |
| Phase IIb |
Dose: 100 μg of GMZ2 (days 0, 28, and 56, 1-year follow-up) Participants: 1,849 children (1 and 5 years old) Year: 2010–2014 |
– efficacy: 14% | Bélard et al., 2011; Sirima et al., 2016b | |
|
Recombinant adenovirus vaccine ChAd63 RH5/MVA RH5 ES adenoviral: ChAd63 and MVA |
Phase Ia |
Dose: – ChAd63 RH5 [5 × 109 viral particles (vp) cf. 5 × 1010 vp] – ChAd63 [5 × 1010 vp + MVA RH5 1 × 108 plaque-forming unit (pfu)]/(5 × 1010 vp + MVA RH5 2 × 108 pfu) Participants: 24 non-exposed adults (19–49 years old) Year: 2014–2015 |
– suitable safety profile – inhibition of parasite growth in vitro (GIA): 36.0 and 50.6% |
Payne et al., 2017 |