疟疾疫苗研究进展

doi:10.11853/j.issn.1003.4692.2014.02.029

摘要/Abstract

摘要： 疟疾是一种世界范围内的传染病, 严重影响人类的身体健康和生命安全。疫苗作为控制乃至消灭传染病的有效手段, 在疟疾研究中受到广泛关注。目前针对疟原虫生活史各期的期特异性疫苗、传播阻断型疫苗、多阶段/多抗原疫苗以及减毒活疫苗都处于研究中。尽管尚无成熟疫苗推入市场, 但一些候选疫苗已进入临床实验, 并产生了非常有希望的结果。该文就疟疾疫苗的研究进展做一综述。

关键词: 疟疾, 疫苗

Abstract: As an infectious disease worldwide, malaria seriously affects human health. Vaccine is an effective way to control and even eradicate infectious disease and has attracted considerable attention in the malaria research. Currently, specific malaria vaccines against human and mosquito stages of the parasite life cycle, transmission-blocking vaccines, multistage/multiantigen vaccines, and live attenuated vaccines are in development. Although no malaria vaccine is put in the market, some vaccine candidates have been in clinical trials, with promising results. The progress in research on malaria vaccine is presented in this article.

Key words: Malaria, Vaccine

中图分类号:

R531.3

王国玲, 甘标, 陆家海. 疟疾疫苗研究进展[J]. 中国媒介生物学及控制杂志, 2014, 25(2): 189-192.

WANG Guoling, GAN Biao, LU Jiahai. Progress in research on malaria vaccine[J]. Chines Journal of Vector Biology and Control, 2014, 25(2): 189-192.

参考文献

[1] World Health Organization. World malaria report 2011
[R]. Geneva:WHO, 2011:12.
[2]　周家莲, 杨恒林. 抗疟药研究现状与发展趋势[J]. 中国病原生物学杂志, 2008, 11(3):865-867.
[3]　郑春福, 陈雅棠. 疟疾核酸免疫的研究进展[J]. 国外医学寄生虫病分册, 2000, 27(1):7-11
[4]　Ballou WR, Rothbard J, Wirtz RA, et al. Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum[J]. Science, 1985, 228(4702):996-999.
[5]　Alonso PL, Sacarlal J, Aponte JJ, et al. Efficacy of the RTS, S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial[J]. Lancet, 2004, 364(9443):1411-1420.
[6]　Bejon P, Lusingu J, Olotu A, et al. Efficacy of RTS, S/AS01E vaccine against malaria in children 5 to 17 months of age[J]. N Engl J Med, 2008, 359(24):2521-2532.
[7]　Sacarlal J, Aide P, Aponte JJ, et al. Long?term safety and efficacy of the RTS, S/AS02A malaria vaccine in Mozambican children[J]. J Infect Dis, 2009, 200(3):329-336.
[8]　季敏. RTS, S/AS01疟疾疫苗Ⅲ期临床研究取得积极结果[J]. 国际生物制品学杂志, 2011, 22(6):296-296.
[9]　Heppner DG Jr, Kester KE, Ockenhouse CF, et al. Towards an RTS, S?based, multi?stage, multiantigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research[J]. Vaccine, 2005, 23(17/18):2243-2250.
[10]　Stewart VA, McGrath SM, Dubois PM, et al. 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[J]. Infect Immun, 2007, 75(5):2283-2290.
[11]　World Health Organization. Initiative for vaccine research: malaria vaccines. 2010[EB/OL].[2011-08-17]. Available at http://www.who.int/vaccine_research/links/Rainbow/en/index.html.
[12]　Cummings JF, Spring MD, Schwenk RJ, et al. Recombinant liver stage antigen-1 (LSA-1) formulated with AS01 or AS02 is safe, elicits high titer antibody and induces IFN?gamma/IL-2 CD4+ T cells but does not protect against experimental Plasmodium falciparum infection[J]. Vaccine, 2010, 28(31):5135-5144.
[13]　Hill AV, Reyes?Sandoval A, O’Hara G, et al. Prime?boost vectored malaria vaccines: progress and prospects[J]. Hum Vaccin, 2010, 6(1):78-83.
[14]　Kaba SA, Brando C, Guo Q, et al. A nonadjuvanted polypeptide nanoparticle vaccine confers longlasting protection against rodent malaria[J]. J Immunol, 2009, 183(11):7268-7277.
[15]　Bergmann?Leitner ES, Mease RM, de La Vega P, et al. Immunization with pre?erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross?species protection against heterologous challenge with Plasmodium berghei[J]. PLoS One, 2010, 5(8):e12294.
[16]　Riley EM, Allen SJ, Wheeler JG, et al. Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity[J]. Parasite Immunol, 1992, 14(3):321-337.
[17]　Thera MA, Doumbo OK, Coulibaly D, et al. Safety and allele?specific immunogenicity of a malaria vaccine in Malian adults: results of a phaseⅠ randomized trial[J]. PLoS Clin Trials, 2006, 1(7):e34.
[18]　Ogutu BR, Apollo OJ, McKinney D, et al. Blood stage malaria vaccine eliciting high antigenspecific antibody concentrations confers no protection to young children in Western Kenya[J]. PLoS One, 2009, 4(3):e4708.
[19]　Hodder AN, Crewther PE, Anders RF. Specificity of the protective antibody response to apical membrane antigen 1[J]. Infect Immun, 2001, 69(5):3286-3294.
[20]　Polley SD, Mwangi T, Kocken CH, et al. Human antibodies to recombinant protein constructs of Plasmodium falciparum apical membrane antigen 1 (AMA1) and their associations with protection from malaria[J]. Vaccine, 2004, 23(5):718-728.
[21]　Dutta S, Lee SY, Batchelor AH, et al. Structural basis of antigenic escape of a malaria vaccine candidate[J]. Proc Natl Acad Sci USA, 2007, 104(30):12488-12493.
[22]　Healer J, Murphy V, Hodder AN, et al. Allelic polymorphisms in apical membrane antigen-1 are responsible for evasion of antibody?mediated inhibition in Plasmodium falciparum[J]. Mol Microbiol, 2004, 52(1):159-168.
[23]　Sagara I, Dicko A, Ellis RD, et al. A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali[J]. Vaccine, 2009, 27(23):3090-3098.
[24]　Thera MA, Doumbo OK, Coulibaly D, et al. Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial[J]. PLoS One, 2010, 5(2):e9041.
[25]　Thera MA, Doumbo OK, Coulibaly D, et al. A field trial to assess a blood?stage malaria vaccine[J]. N Engl J Med, 2011, 365(11):1004-1013.
[26]　Sirima SB, Cousens S, Druilhe P. Protection against malaria by MSP3 candidate vaccine[J]. N Engl J Med, 2011, 365(11):1062-1064.
[27]　Wu Y, Ellis RD, Shaffer D, et al. Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51[J]. PLoS One, 2008, 3(7):e2636.
[28]　Valero MV, Amador LR, Galindo C, et al. Vaccination with SPf66, a chemically synthesized vaccine, against Plasmodium falciparum malaria in Colombia[J]. Lancet, 1993, 341(8847):705-710.
[29]　D’Alessandro U, Leach A, Drakeley CJ, et al. Efficacy trial of malaria vaccine SPf66 in Gambian infants[J]. Lancet, 1995, 346 (8973):462-467.
[30]　Alonso PL, Smith T, Schellenberg JR, et al. Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania[J]. Lancet, 1994, 344(8931):1175-1181.
[31]　Ockenhouse CF, Sun PF, Lanar DE, et al. Phase Ⅰ/Ⅱa safety, immunogenicity, and efficacy trial of NYVAC?Pf7, a pox?vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria[J]. J Infect Dis, 1998, 177(6):1664-1673.
[32]　Kumar S, Epstein JE, Richie TL, et al. A multilateral effort to develop DNA vaccines against falciparum malaria[J]. Trends Parasitol, 2002, 18(3):129-135.
[33]　Freund J, Thomson KJ, Sommer HE, et al. Immunization of rhesus monkeys against malarial infection (P. knowlesi) with killed parasites and adjuvants[J]. Science, 1945, 102(2643):202-204.
[34]　Clyde DF, Most H, McCarthy VC, et al. Immunization of man against sporozite?induced falciparum malaria[J]. Am J Med Sci, 1973, 266(3):169-177.
[35]　Luke TC, Hoffman SL. Rationale and plans for developing a non?replicating, metabolically active, radiation?attenuated Plasmodium falciparum sporozoite vaccine[J]. J Exp Biol, 2003, 206(Pt 21):3803-3808.
[36]　Hoffman SL, Billingsley PF, James E, et al. Development of a metabolically active, nonreplicating sporozoite vaccine to prevent Plasmodium falciparum malaria[J]. Hum Vaccin, 2010, 6(1):97-106.
[37]　Epstein JE, Tewari K, Lyke KE, et al. Live attenuated malaria vacine designed to protect through hepatic CD8+ T cell immunity[J]. Science, 2011, 334(6055):475-480.
[38]　VanBuskirk KM, O’Neill MT, de La Vega P, et al. Preerythrocytic, live?attenuated Plasmodium falciparum vaccine candidates by design[J]. Proc Natl Acad Sci USA, 2009, 106(31):13004-13009.
[39]　Lyke KE, Laurens M, Adams M, et al. Plasmodium falciparum malaria challenge by the bite of aseptic Anopheles stephensi mosquitoes: results of a randomized infectivity trial[J]. PLoS One, 2010, 5(10):e13490.
[40]　Program for Appropriate Technology in Health (PATH), Accelerating Progress Toward Malaria Vaccines[M]. Bethesda, MD:PATH, 2007.
[41]　World Health Organization. New malaria vaccines roadmap targets next generation products by 2030[EB/OL].[2013-11-14].Available at http://www.who.int/mediacentre/news/notes/2013/malaria?vaccines-20131114/en/.