Malaria Vaccines Updates

Table 1: List of malaria vaccines

Type of Vaccines	Name: Compositions	Beneficial / Limitations
Pre-erythrocytic vaccines	1.       RTS,S/AS01E ·         Adenovirus (Ad35) vectored circumsporozoite (CS) protein in prime boost with RTS,S/AS01E ·         Multiple epitope constructs (ME-TRAP); a pre-erythrocytic fusion antigen consisting of 17 B-cell, CD4+, CD8+ T cell epitopes of 6 Pf antigens fused to the T9/96 allele of TRAP (Thrombospondin related adhesion protein)	·         Only the vaccine in Phase 3 clinical trial ·         Low efficacy but decreases mortality
	2.       AdCh63/MVA ME-TRAP ·         Simian Adenovirus (Ad35) encoding ME-TRAP boosted with modified vaccinia virus Ankara (MVA)	·         Long lasting CD8+ T cell responses
	3.       Polyepitope DNA EP1300 ·         DNA vaccine includes multiple epitopes with linker sequences from four pre-erythrocytic antigens CS, SSP2/TRAP, liver stage antigen-1 (LSA-1) and Exported protein-1 (EP-1)	·         Immunogenicity is not enhanced in human as compared to animals
	4.       PfSPZ ·         Metabolically active non-replicating malaria sporozoite vaccine (Pf sporozoites prepared by thawing from liquid nitrogen)	·         Not protective but need to revised in terms of dose and route of administration
	5.       Genetically Attenuated sporozoites-GAS	·         Safe and immunogenic
	6.       FP9 CS/MVA CS ·         Attenuated fowl pox strain (FP9) expressing CS protein boosted with MVA coding CS protein	·         Didn’t boost the T-cell response
	7.       DNA CS/MVA CS ·         Plasmid DNA encoding CS protein replace fowl pox strain (FP9) boosted with MVA coding CS protein	·         Modest T-cell response
	8.       RTS,S/AS02 + MVA CS ·         Boosting RTS,S/AS02 with MVA encoding CS	·         Greater CMI response ·
	9.       CS DNA Immunization or VCL-2510 ·         Gene for full length CS protein in Plasmid DNA	·         No anti-CS antibodies
	10.   MUST DO5 ·         Multi-Stage DNA vaccine operation 5 antigens ·         5 antigens; CS, SSP2/TRAP, LSA-1, LSA-3 and EP-1 adjuvanted with GM-CSF (Granulocyte Macrophage colony stimulating factor)	·         No efficacy
	11.   DNA CS / RTS,S/AS02 ·         DNA vaccine VCL-2510 containing full length CS gene and adjuvanted with RTS,S/AS02	·         No significant improvement than using alone
	12.   RTS,S/AS02 TRAP ·         Combination of CS with TRAP	·         Improve efficacy
	13.   HepB Core Ag CS VLP ·         Also called ICC-1132 or Malariavax ·         Hepatis B core antigen modified to include B-cell and 2 CD4+ epitopes of CS protein	·         No efficacy to sporozoites
	14.   PfCS102 ·         Chemically synthesized Pf CS protein with C-terminus (Amino acids 282-383)	·         Don’t reduce parasitemia
	15.   FP9/MVA polyprotein ·         Prime Boosting with FP9 and MVA viruses with six antigens polyprotein (STARP, TRAP, LSA-1, LSA-3, Pfs16 and EP-1)	·         Low efficacy with sporozoite challenge
	16.   FMP011/AS01B ·         LAS-1 E. coli expressed evaluated with AS01B and AS02A	·         Associated with acute coronary syndrome
Blood Stage (Erythrocytic) vaccines	1.       AdCh63/MVA MSP-1 ·         Pf Merozoite Surface Protein-1 (MSP-1) expressed and boosted with AdCh63 and MVA vectors	·         Low IgG response
	2.       FMP010/AS01B ·         E. coli expressing FVO allele 42kD C terminus of MSP-1 and adjuvants AS01B	·         Good immunogenicity but inadequate clinical efficacy
	3.       FMP2.1/AS02A ·         FMP2.1, in which E. coli expressed Apical membrane antigen (AMA-1) and adjuvant AS02A	·         Strong Th-2 biased response
	4.       FMP2.1/AS01B ·         FMP2.1, in which E. coli expressed Apical membrane antigen (AMA-1) and adjuvant AS01B	·         Adverse effect (rashes after 18 days of vaccination)
	5.       AMA-C1/Alhydrogel + CPG 7909 ·         Pichia pastoris expressed Apical membrane antigen (AMA-1) with both FVO and 3D7 strains and adjuvants Alhydrogel + CPG 7909	·         Reduction of hemoglobin ·
	6.       AdCh63 AMA-1/MVA AMA-1 ·         Apical membrane antigen-1 (AMA-1) expressed and boosted with AdCh63 and MVA vectors	·         CD4+ responses are higher than CD8+ response
	7.       EBA175RII ·         Erythrocyte binding antigen (EBA) in merozoites and highly conserved region of Pf	·         Safe and immunogenic
	8.       SERA5 ·         Blood stage antigen in trophozoites and schizonts (SE36 expressed in E. coli acts as fragment of SERA5 antigen)	·         Safe and 100% seroconversion
	9.       BSAM-2/Alhydrogel +CPG ·         combination vaccine including MSP1 and AMA1 components. It contains a mixture of recombinant proteins with equal parts P. pastoris expressing FVO and 3D7 strains of AMA1 and E. coli expressing the FVO and 3D7 strains of MSP1.	·         Under evaluation
	10.   JAIVAC ·         This combination vaccine consists of MSP1 and EBA175, each of which is an E. coli expressed recombinant protein adjuvanted with Montanide ISA 720	·         Synergistic effects
	11.   GMZ2 ·         L. lactis expressed recombinant fusion protein of glutamate rich protein (GLURP) and MSP-3 adjuvanted with Al(OH)3	·         Acceptable safety ·         Both IgG and memory B cell response
	12.   Combination B (RESA, MSP-1, MSP-2) 13.   FMP1/AS02A 14.   MSP-1-C1/AlOH/AlOH + CPG 15.   MSP2-C1/ISA720 16.   AMA1-C1/ISA720 17.   AMA-FVO 18.   PfCP2.9	·         Already terminated (No succeed)
Gametocyte (Transmission Blocking) Vaccines	1.       Pfs25 ·         Ookinete surface protein Pfs25 ·         The antigen preparations including ookinete surface protein Pfs25, and the gametocyte antigens Pfs48/45 and Pfs230 are used in the TBV vaccines. Pfs25 was the first antigen to progress clinically but the reactogenicity was found to be very low.	·         Low reactogenicity
	2.       Pfs48/45 and Pfs230 ·         Contain the gametocyte antigens Pfs48/45 and Pfs230	·         Low reactogenicity
Combined Vaccines	1.       NMRC-M3V-D/Ad-PfCA Prime/Boost and NMRC-M3V-Ad-PfCA ·         DNA based vaccine containing CS antigen with AMA-1 antigen boosted with Adenovirus-5-vectors	·         Increase CD8+ T cell response but no sterile protection
	2.       CS AMA1 Virosomes ·         Synthetic peptide vaccines ·         Phosphatidylethanolamine (PE) conjugates on the surface of immunopotentiating reconstituted influenza virosomes (PEV301 and PEV302)	·         No sterile protection
	3.       SPf66 ·         Synthetic polypeptide vaccine consisting of CS and merozoites protein1 (MSP1) epitopes adjuvanted with alum	·         Low vaccine efficacy
	4.       RTS,S/AS02 (CS) and FMP-1/AS02 (MSP1) ·         Mixing RTS,S/AS02 (CS) and FMP-1/AS02 (MSP1) with both CS and MSP1 antigens	·         FMP1 gave no protection in the challenge model
P. vivax Vaccines	1.       PvCSP ·         Circumsporozoite protein from P. vivax	·         Under clinical trails
	2.       ChAd63-MVA PvDBP RII and PvDBP RII/GLA-SE ·         Extracellular, cysteine-rich region II (P. vivax Duffy-binding protein; PvDBP_RII)	·         Under clinical trails

References:

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Ockenhouse CF, Regules J, Tosh D, Cowden J, Kathcart A, Cummings J, et al. (2015). Ad35.CS.01 - RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults. PLoS ONE 10(7): e0131571. doi:10.1371/journal.pone.0131571

RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomized, controlled trial. Lancet. 2015 July 04; 386(9988): 31–45.

Salamanca DR, Gómez M, Camargo A, Cuy-Chaparro L, Molina-Franky J, Reyes C, Patarroyo MA and Patarroyo ME (2019). Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines. Front. Microbiol. 10: 2712.

Schwartz L, Brown GV, Genton B and Moorthy VS. A review of malaria vaccine clinical projects based on the WHO rainbow table. Malaria Journal 2012, 11:11

Stewart VA, McGrath SM, Dubois PM, Pau MG, Pascal M, Shott J, Cobb M, Burge R, Larson D, Ware LA, Demoitie M, Weverling GJ, Bayt B, Custes JHHV, Dubois M, Cohen J, Goudsmit J, and Heppner DG. Priming with an Adenovirus 35-Circumsporozoite Protein (CS) Vaccine followed by RTS, S/AS01B Boosting Significantly Improves Immunogenicity to Plasmodium falciparum CS Compared to That with Either Malaria Vaccine Alone. American Society for Microbiology May 2007; 75 (5): 2283–2290.

Stewart VA, McGrath SM, Walsh DS, Davis S, Hess AS, Ware LA, Kester KE, Cummings JF, Burge JR, Voss G, Delchambre M, Garcon N, Tang DB, Cohen JD, Heppner DG. Pre-clinical evaluation of new adjuvant formulations to improve the immunogenicity of the malaria vaccine RTS, S/AS02A.  Vaccine 24: (2006): 6483–6492.

WHO, Background paper on the RTS,S/AS01 malaria vaccine-2015.