Review Article

Malaria Vaccine Development: The Need for Novel Approaches: A Review Article


Background: Although rigorous efforts have substantially decreased the malaria burden through decades, it still threatens the lives of millions of children. Development of an effective vaccine can provide important approach in malaria control strategies. Unfortunately, development of an effective vaccine for falciparum malaria has been hindered by the extreme complexity of malaria parasite biology, complex and diverse parasite genomes, and immune evasion by the parasites as well as the intricate nature of the parasites infection cycle. The aim of this review was to discuss the different approaches to malaria vaccine development until now.

Methods: Scientific databases, including MEDLINE (via PubMed) and SCOPUS were searched up to 30 Jan 2017 and the articles regarding malaria vaccine development were taken into examination.

Results: Several strategies for malaria vaccine development including pre-erythrocytic vaccines, antibody-based subunit vaccines, vectored vaccines, whole sporozoite vaccines, genetically Attenuated parasites and sporozoite subunit vaccine, erythrocytic vaccines, sexual stage vaccine, transmission-blocking vaccine as well as synthetic peptides and conjugate vaccine has been introduced. However, the success has been limited thus far.

Conclusion: Although development of malaria vaccine over the past 70 year has been continued, the discovery, development, and licensing of a malaria vaccine formulation, which meets safety, affordability, accessibility, applicability, and efficacy has not yet been achieved.

Basu S, Sahi PK. Malaria: An Update. Indian J Pediatr. 2017; 84(7):521-528.

WHO. World malaria report 2015: World Health Organization; 2016.

Hill AV. Vaccines against malaria. Philos Trans R Soc Lond B Biol Sci. 2011; 366(1579):2806-14.

Miura K. Progress and prospects for blood-stage malaria vaccines. Expert Rev Vaccines. 2016;15(6):765-81.

Rappuoli R, Aderem A. A 2020 vision for vaccines against HIV, tuberculosis and malaria. Nature. 2011;473(7348):463-9.

Cunningham AL, Garcon N, Leo O et al. Vaccine development: From concept to early clinical testing. Vaccine. 2016;34(52):6655-64.

Gardner MJ, Hall N, Fung E et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002; 419(6906):498-511.

Moore SA, Surgey EG, Cadwgan AM. Malaria vaccines: where are we and where are we going? Lancet Infect Dis. 2002;2(12):737-43.

Rénia L, Goh YS. Malaria parasites: the great escape. Front Immunol. 2016; 7:463

Alger NE, Keshavarz-Valian H. Plasmodium berghei: the effects of suppressor factor on vaccination. Int J Parasitol. 1984;14(3):301-7.

Nussenzweig RS, Vanderberg J, Most H, Orton C. Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. Nature. 1967;216(5111):160-2.

Ballou WR, Cahill CP. Two decades of commitment to malaria vaccine development: Glaxo Smith Kline Biologicals. Am J Trop Med Hyg. 2007;77(6 Suppl):289-95.

Hoffman SL, Goh LM, Luke TC et al. Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites. J Infect Dis. 2002;185(8):1155-64.

Engers HD, Godal T. Malaria vaccine development: current status. Parasitol Today. 1998;14(2):56-64.

D'Antonio LE, Keshavarz-Valian H, Alger NE. Malaria vaccine antigen(s): detergent solubilization, partial isolation, and recovery of immunoprotective activity. Infect Immun. 1984;43(1):442-4.

Sack B, Kappe SH, Sather DN. Towards functional antibody-based vaccines to prevent pre-erythrocytic malaria infection. Expert Rev Vaccines. 2017:16(5):403-414.

Ballou WR. The development of the RTS,S malaria vaccine candidate: challenges and lessons. Parasite Immunol. 2009;31(9):492-500.

Mahmoudi S, Keshavarz H. Efficacy of phase 3 trial of RTS, S/AS01 malaria vaccine: The need for an alternative development plan. Hum Vaccin Immunother. 2017: 13(9):2098-2101.

Reyes-Sandoval A, Berthoud T, Alder N et al. Prime-boost immunization with adenoviral and modified vaccinia virus Ankara vectors enhances the durability and polyfunctionality of protective malaria CD8+ T-cell responses. Infect Immun. 2010;78(1):145-53.

Hill AV, Reyes-Sandoval A, O’Hara G et al. Prime-boost vectored malaria vaccines: progress and prospects. Prime-boost vectored malaria vaccines: progress and prospects. Hum Vaccin. 2010;6(1):78-83.

Singer M, Frischknecht F. Time for Genome Editing: Next-Generation Attenuated Malaria Parasites. Trends Parasitol. 2017;33(3):202-13.

Sigler CI, Leland P, Hollingdale MR. In vitro infectivity of irradiated Plasmodium berghei sporozoites to cultured hepatoma cells. Am J Trop Med Hyg. 1984;33(4):544-7.

Hollingdale MR, Sedegah M. Development of whole sporozoite malaria vaccines. Expert Rev Vaccines. 2017;16(1):45-54.

VanBuskirk KM, O'Neill MT, De La Vega P et al. Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by design. Proc Natl Acad Sci U S A. 2009;106(31):13004-9.

Douradinha B, van Dijk M, van Gemert G-J et al. Immunization with genetically attenuated P52-deficient Plasmodium berghei sporozoites induces a long-lasting effector memory CD8+ T cell response in the liver. J Immune Based Ther Vaccines. 2011;9(1):6.

Cooney LA, Gupta M, Thomas S, et al. Short-lived effector CD8 T cells induced by genetically attenuated malaria parasite vaccination express CD11c. Infect Immun. 2013;81(11):4171-81.

Mikolajczak SA, Lakshmanan V, Fishbaugher M et al. A next-generation genetically attenuated Plasmodium falciparum parasite created by triple gene deletion. Mol Ther. 2014;22(9):1707-15.

van Schaijk BC, Ploemen IH, Annoura T et al. A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites. Elife. 2014;3:e03582.

Sack BK, Keitany GJ, Vaughan AM et al. Mechanisms of stage-transcending protection following immunization of mice with late liver stage-arresting genetically attenuated malaria parasites. PLoS Pathog. 2015;11(5):e1004855.

Bijker EM, Borrmann S, Kappe SH et al. Novel approaches to whole sporozoite vaccination against malaria. Vaccine. 2015;33(52):7462-8.

Roestenberg M, Teirlinck AC, McCall MB et al. Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study. Lancet. 2011;377(9779):1770-6.

Mo AX, Pesce J, Hall BF. Exploring immunological mechanisms of the whole sporozoite vaccination against P. falciparum malaria. Vaccine. 2015;33(25):2851-7.

Luo M, Samandi LZ, Wang Z, Chen ZJ, Gao J. Synthetic nanovaccines for immunotherapy. J Control Release. 2017;263:200-210.

Ballou WR, Rothbard J, Wirtz RA et al. Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum. Science. 1985;228(4702):996-9.

Ellis RD, Sagara I, Doumbo O, Wu Y. Blood stage vaccines for Plasmodium falciparum: current status and the way forward. Hum Vaccin. 2010;6(8):627-34.

Ouattara A, Mu J, Takala-Harrison S et al. Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine. Malar J. 2010;9:175.

Ogutu BR, Apollo OJ, McKinney D et al. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One. 2009;4(3):e4708.

Takala SL, Coulibaly D, Thera MA et al. Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development. Sci Transl Med. 2009;1(2):2ra5.

Eskandarian A-A, Keshavarz H, Basco LK, Mahboudi F. Do mutations in Plasmodium falciparum dihydropteroate synthase and dihydrofolate reductase confer resistance to sulfadoxine-pyrimethamine in Iran? Trans R Soc Trop Med Hyg. 2002;96(1):96-8.

Heidari A, Dittrich S, Jelinek T et al. Genotypes and in vivo resistance of Plasmodium falciparum isolates in an endemic region of Iran. Parasitol Res. 2007;100(3):589-92.

Heidari A, Keshavarz H, Assmar M et al. Genetic diversity in the circumsporozoite protein gene of Plasmodium falciparum from major endemic regions of Iran. Iran J Public Health. 2006;35(3):1-6.

Heidari A, Keshavarz H, Dittrich S et al. Genotyping of Plasmodium falciparum Field Isolates in Major Endemic Region of Iran and Potential Uses in Identification of Field Strains. J Med Sci. 2007;7(2):228-32.

Heidari A, Keshavarz H, Dittrich S, Jelinek T. Allelic Dimorphism of the Plasmodium falciparum Erythrocyte Binding Antigen-175 (EBA-175) Gene in the South-east of Iran. Iran J Parasitol. 2009;4(2):17-22.

Miahipour A, Keshavarz H, Heidari A et al. Assessment of the efficacy of 8 weeks of primaquine for the prevention of relapse in vivax malaria patients using SSCP-PCR and sequencing in south and south-east Iran, 2008–2011. Trans R Soc Trop Med Hyg. 2013; 107(7):420-6.

Heidari A, Keshavarz H, Rokni MB, Jelinek T. Genetic diversity in merozoite surface protein (MSP)-1 and MSP-2 genes of Plasmodium falciparum in a major endemic region of Iran. Korean J Parasitol. 2007;45(1):59-63.

Mardani A, Keshavarz H, Heidari A et al. Genetic polymorphism at the C-terminal domain (region III) of knob-associated histidine-rich protein (KAHRP) of Plasmodium falciparum in isolates from Iran. Parasitol Res. 2011;109(6):1647-52.

Mardani A, Keshavarz H, Heidari A et al. Genetic diversity and natural selection at the domain I of apical membrane antigen-1 (AMA-1) of Plasmodium falciparum in isolates from Iran. Exp Parasitol. 2012;130(4):456-62.

Miahipour A, Keshavarz H, Heidari A et al. Genetic variation of MSP-1 gene in Plasmodium vivax isolated from patients in hormozgan Province, Iran using SSCP-PCR. Iran J Parasitol. 2012;7(4):1-7.

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

Theisen M, Jore MM, Sauerwein R. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine. Expert Rev Vaccines. 2017;16(4):329-36.

Speake C, Pichugin A, Sahu T et al. Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein. PloS One. 2016;11(7):e0159449.

Patarroyo ME, Amador R, Clavijo P et al. A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria. Nature. 1988;332(6160):158-61.

Ramasamy R, Wijesundere DA, Nagendran K, Ramasamy MS. Antibody and clinical responses in volunteers to immunization with malaria peptide-diptheria toxoid conjugates. Clin Exp Immunol. 1995;99(2):168-74.

Wang R, Doolan DL, Le TP et al. Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science. 1998;282(5388):476-80.

McConkey SJ, Reece WH, Moorthy VS et al. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nat Med. 2003;9(6):729-35.

Sanders JW, Ponzio TA. Vectored immunoprophylaxis: an emerging adjunct to traditional vaccination. Trop Dis Travel Med Vaccines. 2017;3:3.

IssueVol 13 No 1 (2018) QRcode
SectionReview Article(s)
Malaria Vaccine candidates Different approaches

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MAHMOUDI S, KESHAVARZ H. Malaria Vaccine Development: The Need for Novel Approaches: A Review Article. Iran J Parasitol. 1;13(1):1-10.