Malaria vaccine 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