Experimental vaccination by single dose sporozoite injection of blood-stage attenuated malaria parasites.

Publisher: EMBO Press Country of Publication: Germany NLM ID: 101487380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE

Publication: 2024- : Heidelberg : EMBO Press
Original Publication: Chichester, West Sussex : Wiley-Blackwell

Malaria Vaccines*/immunology ; Malaria Vaccines*/administration & dosage ; Sporozoites*/immunology ; Plasmodium berghei*/immunology ; Plasmodium berghei*/genetics ; Plasmodium falciparum*/immunology ; Plasmodium falciparum*/genetics ; Plasmodium falciparum*/growth & development ; Vaccines, Attenuated*/immunology ; Vaccines, Attenuated*/administration & dosage ; Vaccines, Attenuated*/genetics ; Malaria*/prevention & control ; Malaria*/parasitology ; Malaria*/immunology; Animals ; Mice ; Vaccination/methods ; Humans ; Gene Deletion ; Female

Malaria vaccination approaches using live Plasmodium parasites are currently explored, with either attenuated mosquito-derived sporozoites or attenuated blood-stage parasites. Both approaches would profit from the availability of attenuated and avirulent parasites with a reduced blood-stage multiplication rate. Here we screened gene-deletion mutants of the rodent parasite P. berghei and the human parasite P. falciparum for slow growth. Furthermore, we tested the P. berghei mutants for avirulence and resolving blood-stage infections, while preserving sporozoite formation and liver infection. Targeting 51 genes yielded 18 P. berghei gene-deletion mutants with several mutants causing mild infections. Infections with the two most attenuated mutants either by blood stages or by sporozoites were cleared by the immune response. Immunization of mice led to protection from disease after challenge with wild-type sporozoites. Two of six generated P. falciparum gene-deletion mutants showed a slow growth rate. Slow-growing, avirulent P. falciparum mutants will constitute valuable tools to inform on the induction of immune responses and will aid in developing new as well as safeguarding existing attenuated parasite vaccines.
(© 2024. The Author(s).)

Akkaya M, Bansal A, Sheehan PW, Pena M, Cimperman CK, Qi CF, Yazew T, Otto TD, Billker O, Miller LH et al (2020) Testing the impact of a single nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor on experimental cerebral malaria in mice. Sci Rep 10:13630. (PMID: 32788672742451610.1038/s41598-020-70617-7)
Aly ASI, Downie MJ, Mamoun CB, Kappe SHI (2010) Subpatent infection with nucleoside transporter 1‐deficient Plasmodium blood stage parasites confers sterile protection against lethal malaria in mice. Cell Microbiol 12:930–938. (PMID: 2008894710.1111/j.1462-5822.2010.01441.x)
Angulo I, Fresno M (2002) Cytokines in the pathogenesis of and protection against malaria. Clin Vaccine Immunol 9:1145–1152. (PMID: 10.1128/CDLI.9.6.1145-1152.2002)
Balu B, Singh N, Maher SP, Adams JH (2010) A genetic screen for attenuated growth identifies genes crucial for intraerythrocytic development of Plasmodium falciparum. PLoS ONE 5:e13282. (PMID: 20949012295259910.1371/journal.pone.0013282)
Bane KS, Lepper S, Kehrer J, Sattler JM, Singer M, Reinig M, Klug D, Heiss K, Baum J, Mueller A-K et al (2016) The actin filament-binding protein coronin regulates motility in Plasmodium sporozoites. PLoS Pathog 12:e1005710. (PMID: 27409081494362910.1371/journal.ppat.1005710)
Bushell E, Gomes AR, Sanderson T, Anar B, Girling G, Herd C, Metcalf T, Modrzynska K, Schwach F, Martin RE et al (2017) Functional profiling of a Plasmodium genome reveals an abundance of essential genes. Cell 170:260–272.e8. (PMID: 28708996550954610.1016/j.cell.2017.06.030)
Butler NS, Schmidt NW, Vaughan AM, Aly AS, Kappe SHI, Harty JT (2011) Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites. Cell Host Microbe 9:451–462. (PMID: 21669394311725410.1016/j.chom.2011.05.008)
Chakravarty S, Shears MJ, James ER, Rai U, Kc N, Conteh S, Lambert LE, Duffy PE, Murphy SC, Hoffman SL (2022) Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites. Malaria J 21:247. (PMID: 10.1186/s12936-022-04261-z)
Crabb BS, Cooke BM, Reeder JC, Waller RF, Caruana SR, Davern KM, Wickham ME, Brown GV, Coppel RL, Cowman AF (1997) Targeted gene disruption shows that knobs enable malaria-infected red cells to cytoadhere under physiological shear stress. Cell 89:287–296. (PMID: 910848310.1016/S0092-8674(00)80207-X)
Craig AG, Grau GE, Janse C, Kazura JW, Milner D, Barnwell JW, Turner G, Langhorne J (2012) The role of animal models for research on severe malaria. PLoS Pathog 8:e1002401. (PMID: 22319438327105610.1371/journal.ppat.1002401)
Dalal S, Klemba M (2007) Roles for two aminopeptidases in vacuolar hemoglobin catabolism in Plasmodium falciparum. J Biol Chem 282:35978–35987. (PMID: 1789524610.1074/jbc.M703643200)
Datoo MS, Natama MH, Somé A, Traoré O, Rouamba T, Bellamy D, Yameogo P, Valia D, Tegneri M, Ouedraogo F et al (2021) Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet 397:1809–1818. (PMID: 33964223812176010.1016/S0140-6736(21)00943-0)
Davies H, Belda H, Broncel M, Ye X, Bisson C, Introini V, Dorin-Semblat D, Semblat J-P, Tibúrcio M, Gamain B et al (2020) An exported kinase family mediates species-specific erythrocyte remodelling and virulence in human malaria. Nat Microbiol 5:848–863. (PMID: 32284562711624510.1038/s41564-020-0702-4)
Deligianni E, Morgan RN, Bertuccini L, Kooij TWA, Laforge A, Nahar C, Poulakakis N, Schüler H, Louis C, Matuschewski K et al (2011) Critical role for a stage‐specific actin in male exflagellation of the malaria parasite. Cell Microbiol 13:1714–1730. (PMID: 2179094510.1111/j.1462-5822.2011.01652.x)
Demarta-Gatsi C, Peronet R, Smith L, Thiberge S, Ménard R, Mécheri S (2017) Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite. Sci Rep 7:9129. (PMID: 28831137556727310.1038/s41598-017-09684-2)
Demarta-Gatsi C, Smith L, Thiberge S, Peronet R, Commere P-H, Matondo M, Apetoh L, Bruhns P, Ménard R, Mécheri S (2016) Protection against malaria in mice is induced by blood stage–arresting histamine-releasing factor (HRF)-deficient parasites. J Exp Med 213:1419–1428. (PMID: 27432939498653510.1084/jem.20151976)
Doolan DL, Dobaño C, Baird JK (2009) Acquired immunity to malaria. Clin Microbiol Rev 22:13–36. (PMID: 19136431262063110.1128/CMR.00025-08)
Edgar RC, Siddiqui G, Malcolm TR, Duffy S, Chowdhury M, Marfurt J, Wirjanata G, Noviyanti R, Daware K, Dans M et al (2023) On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity. mBio 15:e00966–24.
Eling WMC (1980) Plasmodium berghei: premunition, sterile immunity, and loss of immunity in mice. Exp Parasitol 49:89–96. (PMID: 698559310.1016/0014-4894(80)90060-0)
Epstein JE, Paolino KM, Richie TL, Sedegah M, Singer A, Ruben AJ, Chakravarty S, Stafford A, Ruck RC, Eappen AG et al (2017) Protection against Plasmodium falciparum malaria by PfSPZ vaccine. Jci Insight 2:e89154. (PMID: 28097230521406710.1172/jci.insight.89154)
Farr EB, Sattler JM, Frischknecht F (2021) SPOT: a web-tool enabling swift profiling of transcriptomes. Bioinformatics 38:284–285. (PMID: 3428902410.1093/bioinformatics/btab541)
Gomes AR, Bushell E, Schwach F, Girling G, Anar B, Quail MA, Herd C, Pfander C, Modrzynska K, Rayner JC et al (2015) A genome-scale vector resource enables high-throughput reverse genetic screening in a malaria parasite. Cell Host Microbe 17:404–413. (PMID: 25732065436295710.1016/j.chom.2015.01.014)
Good MF, Stanisic DI (2020) Whole parasite vaccines for the asexual blood stages of Plasmodium. Immunol Rev 293:270–282. (PMID: 3170955810.1111/imr.12819)
Goswami D, Patel H, Betz W, Armstrong J, Camargo N, Patil A, Chakravarty S, Murphy SC, Sim BKL, Vaughan AM et al (2024) A replication competent Plasmodium falciparum parasite completely attenuated by dual gene deletion. EMBO Mol Med 16:723–754. (PMID: 385147911101881910.1038/s44321-024-00057-7)
Grüring C, Moon RW, Lim C, Holder AA, Blackman MJ, Duraisingh MT (2014) Human adapted P. knowlesi: a new malaria model system. Cell Microbiol 16:612–620. (PMID: 24506567400406210.1111/cmi.12275)
Hoffmann A, Helluy X, Fischer M, Mueller A-K, Heiland S, Pham M, Bendszus M, Pfeil J (2017) In vivo tracking of edema development and microvascular pathology in a model of experimental cerebral malaria using magnetic resonance imaging. J Vis Exp 124:55334.
Hoffmann A, Pfeil J, Alfonso J, Kurz FT, Sahm F, Heiland S, Monyer H, Bendszus M, Mueller A-K, Helluy X et al (2016) Experimental cerebral malaria spreads along the rostral migratory stream. PLoS Pathog 12:e1005470. (PMID: 26964100478621410.1371/journal.ppat.1005470)
Ishizuka AS, Lyke KE, DeZure A, Berry AA, Richie TL, Mendoza FH, Enama ME, Gordon IJ, Chang L-J, Sarwar UN et al (2016) Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nat Med 22:614–623. (PMID: 271589071129473310.1038/nm.4110)
Janse CJ, Franke-Fayard B, Mair GR, Ramesar J, Thiel C, Engelmann S, Matuschewski K, Gemert GJ, van, Sauerwein RW, Waters AP (2006) High efficiency transfection of Plasmodium berghei facilitates novel selection procedures. Mol Biochem Parasit 145:60–70. (PMID: 10.1016/j.molbiopara.2005.09.007)
Kehrer J, Singer M, Lemgruber L, Silva PAGC, Frischknecht F, Mair GR (2016) A putative small solute transporter is responsible for the secretion of G377 and TRAP-containing secretory vesicles during Plasmodium gamete egress and sporozoite motility. PLoS Pathog 12:e1005734. (PMID: 27427910494885310.1371/journal.ppat.1005734)
Kennedy M, Fishbaugher ME, Vaughan AM, Patrapuvich R, Boonhok R, Yimamnuaychok N, Rezakhani N, Metzger P, Ponpuak M, Sattabongkot J et al (2012) A rapid and scalable density gradient purification method for Plasmodium sporozoites. Malaria J 11:421. (PMID: 10.1186/1475-2875-11-421)
Kimmel J, Schmitt M, Sinner A, Jansen PWTC, Mainye S, Ramón-Zamorano G, Toenhake CG, Wichers-Misterek JS, Cronshagen J, Sabitzki R et al (2023) Gene-by-gene screen of the unknown proteins encoded on Plasmodium falciparum chromosome 3. Cell Syst 14:9–23.e7. (PMID: 3665739310.1016/j.cels.2022.12.001)
Klug D, Kehrer J, Frischknecht F, Singer M (2018) A synthetic promoter for multi-stage expression to probe complementary functions of Plasmodium adhesins. J Cell Sci 131:jcs210971. (PMID: 3023722010.1242/jcs.210971)
Kublin JG, Mikolajczak SA, Sack BK, Fishbaugher ME, Seilie A, Shelton L, VonGoedert T, Firat M, Magee S, Fritzen E et al (2017) Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects. Sci Transl Med 9:eaad9099. (PMID: 2805315910.1126/scitranslmed.aad9099)
Kurtovic L, Reiling L, Opi DH, Beeson JG (2021) Recent clinical trials inform the future for malaria vaccines. Commun Med 1:26. (PMID: 35602185905326310.1038/s43856-021-00030-2)
Langhorne J, Buffet P, Galinski M, Good M, Harty J, Leroy D, Mota MM, Pasini E, Renia L, Riley E et al (2011) The relevance of non-human primate and rodent malaria models for humans. Malar J 10:23. (PMID: 21288352304172010.1186/1475-2875-10-23)
Laurentino EC, Taylor S, Mair GR, Lasonder E, Bartfai R, Stunnenberg HG, Kroeze H, Ramesar J, Franke‐Fayard B, Khan SM et al (2011) Experimentally controlled downregulation of the histone chaperone FACT in Plasmodium berghei reveals that it is critical to male gamete fertility. Cell Microbiol 13:1956–1974. (PMID: 21899698342985810.1111/j.1462-5822.2011.01683.x)
Lim MY-X, LaMonte G, Lee MCS, Reimer C, Tan BH, Corey V, Tjahjadi BF, Chua A, Nachon M, Wintjens R et al (2016) UDP-galactose and acetyl-CoA transporters as Plasmodium multidrug resistance genes. Nat Microbiol 1:16166. (PMID: 27642791557599410.1038/nmicrobiol.2016.166)
Lin J, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, Ravelli RBG, Aime E, Capuccini B, Mommaas-Kienhuis AM et al (2015) Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance. J Exp Med 212:893–903. (PMID: 25941254445112210.1084/jem.20141731)
Lindner SE, Swearingen KE, Shears MJ, Walker MP, Vrana EN, Hart KJ, Minns AM, Sinnis P, Moritz RL, Kappe SHI (2019) Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites. Nat Commun 10:4964. (PMID: 31673027682342910.1038/s41467-019-12936-6)
Lyke KE, Ishizuka AS, Berry AA, Chakravarty S, DeZure A, Enama ME, James ER, Billingsley PF, Gunasekera A, Manoj A et al (2017) Attenuated PfSPZ vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection. Proc Natl Acad Sci USA 114:2711–2716. (PMID: 28223498534761010.1073/pnas.1615324114)
Mathieu C, Demarta‐Gatsi C, Porcherie A, Brega S, Thiberge S, Ronce K, Smith L, Peronet R, Amino R, Ménard R et al (2015) Plasmodium berghei histamine‐releasing factor favours liver‐stage development via inhibition of IL‐6 production and associates with a severe outcome of disease. Cell Microbiol 17:542–558. (PMID: 2532944110.1111/cmi.12382)
Matthews K, Kalanon M, Chisholm SA, Sturm A, Goodman CD, Dixon MWA, Sanders PR, Nebl T, Fraser F, Haase S et al (2013) The Plasmodium translocon of exported proteins (PTEX) component thioredoxin‐2 is important for maintaining normal blood‐stage growth. Mol Microbiol 89:1167–1186. (PMID: 2386952910.1111/mmi.12334)
Matz JM, Matuschewski K, Kooij TWA (2013) Two putative protein export regulators promote Plasmodium blood stage development in vivo. Mol Biochem Parasit 191:44–52. (PMID: 10.1016/j.molbiopara.2013.09.003)
Minassian AM, Silk SE, Barrett JR, Nielsen CM, Miura K, Diouf A, Loos C, Fallon JK, Michell AR, White MT et al (2021) Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med 2:701–719.e19. (PMID: 3422340210.1016/j.medj.2021.03.014)
Mohring F, Hart M, Patel A, Baker D, Moon R (2020) CRISPR-Cas9 genome editing of Plasmodium knowlesi. Bio-protocol 10:e3522. (PMID: 33654746784260510.21769/BioProtoc.3522)
Mordmüller B, Sulyok M, Egger-Adam D, Resende M, Jongh WA, de, Jensen MH, Smedegaard HH, Ditlev SB, Soegaard M, Poulsen L et al (2019) First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria. Clin Infect Dis 69:ciy1140. (PMID: 10.1093/cid/ciy1140)
Mordmüller B, Surat G, Lagler H, Chakravarty S, Ishizuka AS, Lalremruata A, Gmeiner M, Campo JJ, Esen M, Ruben AJ et al (2017) Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature 542:445–449. (PMID: 281993051090648010.1038/nature21060)
Mueller A-K, Labaied M, Kappe SHI, Matuschewski K (2005) Genetically modified Plasmodium parasites as a protective experimental malaria vaccine. Nature 433:164–167. (PMID: 1558026110.1038/nature03188)
Murphy SC, Vaughan AM, Kublin JG, Fishbauger M, Seilie AM, Cruz KP, Mankowski T, Firat M, Magee S, Betz W et al (2022) A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection. Sci Transl Med 14:eabn9709. (PMID: 360016801042333510.1126/scitranslmed.abn9709)
Nevagi RJ, Good MF, Stanisic DI (2021) Plasmodium infection and drug cure for malaria vaccine development. Expert Rev Vaccines 20:163–183. (PMID: 3342850510.1080/14760584.2021.1874923)
Nussenzweig RS, Vanderberg J, Most H, Orton C (1967) Protective immunity produced by the injection of X-irradiated sporozoites of Plasmodium berghei. Nature 216:160–162. (PMID: 605722510.1038/216160a0)
O’Flaherty K, Roe M, Fowkes FJI (2022) The role of naturally acquired antimalarial antibodies in subclinical Plasmodium spp. infection. J Leukoc Biol 111:1097–1105. (PMID: 3506018510.1002/JLB.5MR1021-537R)
Peng D, Tarleton R (2015) EuPaGDT: a web tool tailored to design CRISPR guide RNAs for eukaryotic pathogens. Microb Genom 1:e000033. (PMID: 283488175320623)
Portugal S, Tran TM, Ongoiba A, Bathily A, Li S, Doumbo S, Skinner J, Doumtabe D, Kone Y, Sangala J et al (2016) Treatment of chronic asymptomatic Plasmodium falciparum infection does not increase the risk of clinical malaria upon reinfection. Clin Infect Dis 64:645–653. (PMID: 607551310.1093/cid/ciw849)
Postma NS, Hermsen CC, Crommelin DJA, Zuidema J, Eling WMC (1999) Treatment with recombinant human tumour necrosis factor-α reduces parasitaemia and prevents Plasmodium berghei K173-induced experimental cerebral malaria in mice. Parasitology 118:7–15. (PMID: 1007065610.1017/S0031182098003552)
Purcell LA, Wong KA, Yanow SK, Lee M, Spithill TW, Rodriguez A (2008) Chemically attenuated Plasmodium sporozoites induce specific immune responses, sterile immunity and cross-protection against heterologous challenge. Vaccine 26:4880–4884. (PMID: 18672017256017510.1016/j.vaccine.2008.07.017)
Roestenberg M, Walk J, Boor SC, van der, Langenberg MCC, Hoogerwerf M-A, Janse JJ, Manurung M, Yap XZ, García AF, Koopman JPR et al (2020) A double-blind, placebo-controlled phase 1/2a trial of the genetically attenuated malaria vaccine PfSPZ-GA1. Sci Transl Med 12:eaaz5629. (PMID: 3243484710.1126/scitranslmed.aaz5629)
Rosenkranz M, Fürle K, Hibbert J, Ulmer A, Ali A, Giese T, Blank A, Haefeli WE, Böhnlein E, Lanzer M et al (2023) Multifunctional IgG/IgM antibodies and cellular cytotoxicity are elicited by the full-length MSP1 SumayaVac-1 malaria vaccine. NPJ Vaccines 8:112. (PMID: 375586731041256610.1038/s41541-023-00701-2)
RTS,S Clinical Trials Partnership (2015) 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 randomised, controlled trial. Lancet 386:31–45. (PMID: 10.1016/S0140-6736(15)60721-8)
RTS,S Clinical Trials Partnership, Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BGNO, Kabwende AL, Adegnika AA, Mordmüller B, Issifou S et al (2012) A phase 3 trial of RTS,S/AS01 malaria vaccine in African Infants. New Engl J Med 367:2284–2295. (PMID: 10.1056/NEJMoa1208394)
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682. (PMID: 2274377210.1038/nmeth.2019)
Seder RA, Chang L-J, Enama ME, Zephir KL, Sarwar UN, Gordon IJ, Holman LA, James ER, Billingsley PF, Gunasekera A et al (2013) Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341:1359–1365. (PMID: 2392994910.1126/science.1241800)
Sirima SB, Ouédraogo A, Tiono AB, Kaboré JM, Bougouma EC, Ouattara MS, Kargougou D, Diarra A, Henry N, Ouédraogo IN et al (2022) A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria. Sci Transl Med 14:eabj3776. (PMID: 364759051004199610.1126/scitranslmed.abj3776)
Sissoko MS, Healy SA, Katile A, Zaidi I, Hu Z, Kamate B, Samake Y, Sissoko K, Mwakingwe-Omari A, Lane J et al (2022) Safety and efficacy of a three-dose regimen of Plasmodium falciparum sporozoite vaccine in adults during an intense malaria transmission season in Mali: a randomised, controlled phase 1 trial. Lancet Infect Dis 22:377–389. (PMID: 3480111210.1016/S1473-3099(21)00332-7)
Spaccapelo R, Janse CJ, Caterbi S, Franke-Fayard B, Bonilla JA, Syphard LM, Cristina MD, Dottorini T, Savarino A, Cassone A et al (2010) Plasmepsin 4-deficient Plasmodium berghei are virulence attenuated and induce protective immunity against experimental malaria. Am J Pathol 176:205–217. (PMID: 20019192279788310.2353/ajpath.2010.090504)
Stanisic DI, Fink J, Mayer J, Coghill S, Gore L, Liu XQ, El-Deeb I, Rodriguez IB, Powell J, Willemsen NM et al (2018) Vaccination with chemically attenuated Plasmodium falciparum asexual blood-stage parasites induces parasite-specific cellular immune responses in malaria-naïve volunteers: a pilot study. Bmc Med 16:184. (PMID: 30293531617457210.1186/s12916-018-1173-9)
Stanisic DI, Ho M-F, Nevagi R, Cooper E, Walton M, Islam MT, Hussein WM, Skwarczynski M, Toth I, Good MF (2021) Development and evaluation of a cryopreserved whole-parasite vaccine in a rodent model of blood-stage malaria. Mbio 12:e02657–21. (PMID: 34663097852433610.1128/mBio.02657-21)
Su Z, Stevenson MM (2000) Central role of endogenous gamma interferon in protective immunity against blood-stage Plasmodium chabaudi AS infection. Infect Immun 68:4399–4406. (PMID: 108998369833310.1128/IAI.68.8.4399-4406.2000)
Su Z, Stevenson MM (2002) IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice. J Immunol 168:1348–1355. (PMID: 1180167510.4049/jimmunol.168.3.1348)
Swearingen KE, Lindner SE, Shi L, Shears MJ, Harupa A, Hopp CS, Vaughan AM, Springer TA, Moritz RL, Kappe SHI et al (2016) Interrogating the Plasmodium sporozoite surface: identification of surface-exposed proteins and demonstration of glycosylation on CSP and TRAP by mass spectrometry-based proteomics. PLoS Pathog 12:e1005606. (PMID: 27128092485141210.1371/journal.ppat.1005606)
Ting L-M, Gissot M, Coppi A, Sinnis P, Kim K (2008) Attenuated Plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity. Nat Med 14:954–958. (PMID: 18758447393781810.1038/nm.1867)
Tiono AB, Nébié I, Anagnostou N, Coulibaly AS, Bowyer G, Lam E, Bougouma EC, Ouedraogo A, Yaro JBB, Barry A et al (2018) First field efficacy trial of the ChAd63 MVA ME-TRAP vectored malaria vaccine candidate in 5-17 months old infants and children. PLoS ONE 13:e0208328. (PMID: 30540808629113210.1371/journal.pone.0208328)
Uchida J, Lee Y, Hasegawa M, Liang Y, Bradney A, Oliver JA, Bowen K, Steeber DA, Haas KM, Poe JC et al (2004) Mouse CD20 expression and function. Int Immunol 16:119–129. (PMID: 1468806710.1093/intimm/dxh009)
van Schaijk BCL, Ploemen IHJ, Annoura T, Vos MW, Foquet L, van Gemert G-J, Chevalley-Maurel S, van de Vegte-Bolmer M, Sajid M, Franetich J-F et al (2014) A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites. eLife 3:e03582. (PMID: 25407681427344010.7554/eLife.03582)
Voza T, Vigário AM, Belnoue E, Grüner AC, Deschemin J-C, Kayibanda M, Delmas F, Janse CJ, Franke-Fayard B, Waters AP et al (2005) Species-specific inhibition of cerebral malaria in mice coinfected with Plasmodium spp. Infect Immun 73:4777–4786. (PMID: 16040990120124510.1128/IAI.73.8.4777-4786.2005)
Waters AP, Thomas AW, van Dijk MR, Janse CJ (1997) Transfection of malaria parasites. Methods 13:134–147. (PMID: 940519710.1006/meth.1997.0506)
Webster R, Sekuloski S, Odedra A, Woolley S, Jennings H, Amante F, Trenholme KR, Healer J, Cowman AF, Eriksson EM et al (2021) Safety, infectivity and immunogenicity of a genetically attenuated blood-stage malaria vaccine. BMC Med 19:293. (PMID: 34802442860625010.1186/s12916-021-02150-x)
Zhang M, Wang C, Otto TD, Oberstaller J, Liao X, Adapa SR, Udenze K, Bronner IF, Casandra D, Mayho M et al (2018) Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science 360:eaap7847. (PMID: 29724925636094710.1126/science.aap7847)

TTU 03.813 Deutsches Zentrum für Infektionsforschung (DZIF); FR2140/10-1 Deutsche Forschungsgemeinschaft (DFG); SFB 1129 Deutsche Forschungsgemeinschaft (DFG); FR2140/6-1 Deutsche Forschungsgemeinschaft (DFG); Az 92393 Volkswagen Foundation (VolkswagenStiftung)

Keywords: Plasmodium; Genetic Attenuation; Malaria; Vaccine; Virulence

0 (Malaria Vaccines)
0 (Vaccines, Attenuated)

Date Created: 20240805 Date Completed: 20240913 Latest Revision: 20240925

20250114

PMC11392930

10.1038/s44321-024-00101-6

39103697