Chapter 46 : Immune Intervention in Malaria

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Immune Intervention in Malaria, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816872/9781555815141_Chap46-1.gif /docserver/preview/fulltext/10.1128/9781555816872/9781555815141_Chap46-2.gif


A parasite’s life cycle is complex, hence there are three major targets of vaccines. Overall, each of these stages is antigenically, morphologically, and biochemically distinct so that different researchers have focused on different stages, with different goals: sporozoites for prevention of infection or early liver stage development, erythrocytic stages to limit malaria morbidity and mortality, and the sexual stages to reduce transmission to others. This chapter reviews vaccine development efforts separated by stages of infection. A number of immunization studies using experimental animal models and humans performed in the 1960s and 1970s demonstrated that protective immunity against preerythrocytic stages of malaria parasites could be induced by immunization with irradiation-attenuated sporozoites. Since immunization of humans with radiation-attenuated sporozoites has been shown to induce consistently strong protective immunity and considering that this efficacy has not been matched by immunization with available subunit vaccines, some researchers have proposed the implementation of a large-scale vaccination program using attenuated sporozoites. The merozoite proteins can elicit immune responses that prevent red cell invasion and development while the red cell surface proteins can induce responses that promote elimination of infected red cells and limit binding to host cells. There has been an ongoing discussion as to whether a vaccine should be targeted to replicating the type of immunity found in a semi-immune adult or whether the goal of a vaccine should be to elicit responses superior to the partial immunity conferred by long-term and repeated exposure to malaria infection.

Citation: Long C, Zavala F. 2011. Immune Intervention in Malaria, p 587-597. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch46

Key Concept Ranking

Major Histocompatibility Complex
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Life cycle of malaria parasites.

Citation: Long C, Zavala F. 2011. Immune Intervention in Malaria, p 587-597. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch46
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Development of in human red blood cells. Merozoites attach to and invade mature red blood cells (RBCs) and the parasite develops in a parasitophorous vacuole through ring (0 to 24 hours), trophozoite (24 to 36 hours), and schizont stages (40 to 48 hours). In midcycle, membranous structures appear in the RBC cytoplasm and deformations (knobs) appear on the RBC membrane. These knobs include parasite-encoded proteins in the erythrocyte membrane protein-1 (PfEMP1) family as well as other proteins. After approximately 48 hours, the infected RBC ruptures and releases 16 to 32 daughter merozoites. Taken from Maier and colleagues ( ).

Citation: Long C, Zavala F. 2011. Immune Intervention in Malaria, p 587-597. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch46
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Illustration of a malaria merozoite as well as major proteins located on the merozoite surface, the rhoptries, and the micronemes. Taken from Richards and Beeson ( ).

Citation: Long C, Zavala F. 2011. Immune Intervention in Malaria, p 587-597. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch46
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Adams,, J. H.,, B.K. Sim,, S. A. Dolan,, X. Fang,, D. C. C, and L. H. Miller. 1992. A family of erythrocyte binding proteins of malaria parasites. Proc. Natl. Acad. Sci. USA 89:70857089.
2. Alonso,, P. L.,, J. Sacarlal,, J. J Aponte,, A. Leach,, E. Macete,, J. Milman,, I. Mandomando,, B. Spiessens,, C. Guinovart,, M. Espasa,, Q. Bassat,, P. Aide,, O. Ofori-Anyinam,, M. M. Navia,, S. Corachan,, M. Ceuppens,, M. C. Dubois,, M. A. Demoitie,, F. Dubovsky,, C. Menendez,, N. Tornieporth,, W. R. Ballou,, R. Thompson, and, J. Cohen. 2004. Efficacy of the RTS, S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364:14111420.
3. Bejon, P.,, J. Lusingu,, A. Olotu,, A. Leach,, M. Lievens,, J. Vekemans,, S. Mshamu,, T. Lang,, J. Gould,, M. C. Dubois,, M. A. Demoitie,, J. F. Stallaert,, P. Vansadia,, T. Carter,, P. Njuguna,, K. O. Awuondo,, A. Malabeja,, O. Abdul,, S. Gesase,, N. Mturi,, C. J. Drakeley,, B. Savarese,, T. Villafana,, W. R. Ballou,, J. Cohen,, E. M. Riley,, M. M. Lemnge,, K. Marsh, and, L. von Seidlein. 2008. Efficacy of RTS, S/AS01E vaccine against malaria in children 5 to 17 months of age. N. Engl. J. Med. 359:25212532.
4. Bojang,, K. A.,, P.J. Milligan,, M. Pinder,, L. Vigneron,, A. Alloueche,, K. E. Kester,, W. R. Ballou,, D. J. Conway,, W. H. Reece,, P. Gothard,, L. Yamuah,, M. Delchambre,, G. Voss,, B. M. Greenwood,, A. Hill,, K. P. McAdam,, N. Tornieporth,, J. D. Cohen, and, T. Doherty. 2001. Efficacy of RTS, S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in the Gambia: a randomised trial. Lancet 358:19271934.
5. Bouharoun-Tayoun, H.,, P. Attanath,, A. Sabchareon,, T. Chongsuphajaisiddhi,, and P. Druilhe. 1990. Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J. Exp, Med. 172:16331641.
6. Bull,, P. C,, B.S. Lowe,, M. Kortok,, C. S Molyneux,, C. I Newbold,, and K. Marsh. 1998. Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat. Med. 4:358360.
7. Camus, D.,, and T.J. Hadley. 1985. A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science 230:553556.
8. Chowdhury, D. R.,, E. Angov,, T. Kariuki,, and N. Kumar. 2009. A potent malaria transmission blocking vaccine based on codon harmonized full length Pfs48/45 expressed in Escherichia coli. PLoS ONE 4:e6352.
9. Clyde, D. F. 1975. Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites. Am. J. Trap. Med. Hyg. 24:397401.
10. Cohen, J.,, V. Nussenzweig,, R. Nussenzweig,, J. Vekemans,, and A. Leach. 2009. From the circumsporozoite protein to the RTS, S/AS candidate vaccine. Hum Vaccine 6:9096.
11. Cohen, S.,, I.A. McGregor,, and S. Carrington. 1961. Gammaglobulin and acquired immunity to human malaria. Nature 192:733737.
12. Cowman, A. F.,, and B.S. Crabb. 2006. Invasion of red blood cells by malaria parasites. Cell 124:755766.
13. Daly, T. M.,, and C. A. Long. 1993. Arecombinant 15-kilodalton carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in mice. Infect. Immun. 61:24622467.
14. Deans,, J. A.,, A.W. Thomas,, T. Alderson, and, S. Cohen. 1984. Biosynthesis of a putative protective Plasmodium knowlesi merozoite antigen. Mol. Biochem. Parasitol. 11:189204.
15. Dinglasan, R. R.,, and M. Jacobs-Lorena. 2008. Flipping the paradigm on malaria transmission-blocking vaccines. Trends Parasitol. 24:364370.
16. Dobano, C, and, D.L. Doolan. 2007. Identification of minimal CD8+ and CD4+ T cell epitopes in the Plasmodium yoelii hepatocyte erythrocyte protein 17kDa. Mol. Immunol. 44:30373048.
17. Doolan,, D. L.,, M. Sedegah,, R. C Hedstrom,, P. Hobart,, Y. Charoenvit,, and S.L. Hoffman. 1996. Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon gamma-, and nitric oxide-dependent immunity. J. Exp. Med. 183:17391746.
18. Edstein,, M. D.,, B.M. Kotecka,, K. L. Anderson,, D. J. Pombo,, D. E. Kyle,, K. H. Rieckmann, and, M.F. Good. 2005. Lengthy antimalarial activity of atovaquone in human plasma following atovaquone-proguanil administration. Antimicrob. Agents Chemother. 49:44214422.
19. Esen,, M.,, P.G. Kremsner,, R. Schleucher,, M. Gassler,, E. B. Imoukhuede,, N. Imbault,, O. Leroy,, S. Jepsen,, B. W. Knudsen,, M. Schumm,, J. Knobloch,, M. Theisen, and, B. Mordmuller. 2009. Safety and immunogenicity of GMZ2-a MSP3-GLURP fusion protein malaria vaccine candidate. Vaccine. 27:68626868.
20. Fowkes,, F. J.,, J.S. Richards,, J.A. Simpson,, and J.G. Beeson. 2010. The relationship between anti-merozoite antibodies and incidence of Plasmodium falciparum malaria: a systematic review and meta-analysis. PLoS Med. 7:e1000218.
21. Fried, M.,, and P.E. Duffy. 1996. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272:15021504.
22. Galinski, M. R.,, and J.W. Barnwell. 2008. Plasmodium vivax: who cares? Malar. J. 7:S9.
23. Genton,, B., I. Betuela,, I. Felger, F. Al-Yaman,, R. F. Anders,, A. Saul,, L. Rare,, M. Baisor,, K. Lorry,, G. V. Brown,, D. Pye,, D. O. Irving,, T. A. Smith,, H. P. Beck, and, M. P. Alpers. 2002. A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea. J. Infect. Dis. 185:820827.
24. Good,, M. F.,, D. Pombo,, I. A Quakyi,, E. M. Riley,, R. A. Houghten,, A. Menon,, D. W. Alling,, J. A. Berzofsky, and, L.H. Miller. 1988. Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule. Proc. Natl. Acad. Sci. USA 85:11991203.
25. Grun, J. L.,, and W. P. Weidanz. 1981. Immunity to Plasmodium chabaudi adami in the B-cell-deficient mouse. Nature 290:143145.
26. Hill,, A. V.,, A. Reyes-Sandoval,, G. O’Hara,, K. Ewer,, A. Lawrie,, A. Goodman,, A. Nicosra,, A. Folgori,, S. Colloca,, R. Cortese,, S. C. Gilbert, and, S. J. Draper. 2010. Prime-boost vectored malaria vaccines: progress and prospects. Hum. Vaccine 6:7883.
27. Holder, A. A. 2009. The carboxy-terminus of merozoite surface protein 1: structure, specific antibodies and immunity to malaria. Parasitology 136:14451456.
28. Hviid, L.,, and A. Salanti. 2007. VAR2CSA and protective immunity against pregnancy-associated Plasmodium falciparum malaria. Parasitology 134:18711876.
29. Kester, K. E.,, J.F. Cummings,, O. Ofori-Anyinam,, C. F. Ockenhouse,, U. Krzych,, P. Moris,, R. Schwenk,, R. A. Nielsen,, Z. Debebe,, E. Pinelis,, L. Juompan,, J. Williams,, M. Dowler,, V. A. Stewart,, R. A. Wirtz,, M. C. Dubois,, M. Lievens,, J. Cohen,, W. R. Ballou, and D. G. G, Jr. 2009. Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS, S/AS01B and RTS, S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection. J. Infect. Dis. 200:337346.
30. Khusmith, S.,, Y. Charoenvit,, S. Kumar,, M. Sedegah,, R.L. Beaudoin,, and S. L. Hoffman. 1991. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science 252:715718.
31. Kraemer, S. M.,, and J.D. Smith. 2006. A family affair: var genes, PfEMP1 binding, and malaria disease. Curr. Opin. Microbiol. 9:374380.
32. Kumar,, K. A.,, G. Sano,, S. Boscardin,, R. S. Nussenzweig,, M. C. Nussenzweig,, F. Zavala, and, V. Nussenzweig. 2006. The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. Nature 444:937940.
33. Li, S.,, M. Rodrigues,, D. Rodriguez,, J. R Rodriguez,, M. Esteban,, P. Palese,, R. S Nussenzweig, and, F. Zavala. 1993. Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. Proc. Natl. Acad. Sci. USA 90:52145218.
34. Limbach, K. J.,, and T.L. Richie. 2009. Viral vectors in malaria vaccine development. Parasite Immunol. 31:501519.
35. Luke, T. C.,, and S.L. Hoffman. 2003. Rationale and plans for developing a non-replicating, metabolically active, radiation-attenuated Plasmodium falciparum sporozoite vaccine. J. Exp. Biol. 206:38033808.
36. Maier, A. G.,, B. M. Cooke,, A. R Cowman,, and L. Tilley. 2009. Malaria parasite proteins that remodel the host erythrocyte. Nat. Rev. Microbiol. 7:341-354.
37. Malkin, E. M.,, A.P. Durbin,, D. J. Diemert,, J. Sattabongkot,, Y. Wu,, K. Miura,, C. A. Long,, L. Lambert,, A. P. Miles,, J. Wang,, A. Stowers,, L. H. Miller,, and A. Saul. 2005. Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria. Vaccine 23:31313138.
38. Marsh, K.,, and S. Kinyanjui. 2006. Immune effector mechanisms in malaria. Parasite Immunol. 28:5160.
39. McCarthy, J. S.,, and M. F. Good. Whole parasite blood stage malaria vaccines: a convergence of evidence. Hum. Vaccine 6:114123.
40. Mikolajczak, S. A.,, A. S. Aly,, and S.H. Kappe. 2007. Preerythrocytic malaria vaccine development. Curr. Opin. Infect. Dis. 20:461466.
41. Nussenzweig, R. S.,, J. Vanderberg,, H. Most,, and C. Orton. 1967. Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. Nature 216:160162.
42. Nussenzweig, V.,, and R. S. Nussenzweig. 1989. Rationale for the development of an engineered sporozoite malaria vaccine. Adv. Immunol. 45:283334.
43. Oeuvray, C,, H. Bouharoun-Tayoun,, H. Gras-Masse,, E. Bottius,, T. Kaidoh,, M. Aikawa,, M. C Filgueira,, A. Tartar,, and P. Druilhe. 1994. Merozoite surface protein-3: a malaria protein inducing antibodies that promote Plasmodium falciparum killing by cooperation with blood monocytes. Blood 84:15941602.
44. Ogutu,, B. R.,, O. J. Apollo,, D. McKinney,, W. Okoth,, J. Siangla,, F. Dubovsky,, K. Tucker,, J. N. Waitumbi,, C. Diggs,, J. Wittes,, E. Malkin,, A. Leach,, L. A. Soisson,, J. B. Milman,, L. Otieno,, C. A. Holland,, M. Polhemus,, S. A. Remich,, C. F. Ockenhouse,, J. Cohen,, W. R. Ballou,, S. K. Martin,, E. Angov,, V. A. Stewart,, J. A. Lyon,, D. G. Heppner, and, M. R. Withers. 2009. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS ONE 4:e4708.
45. Pleass, R. J. 2009. Fc-receptors and immunity to malaria: from models to vaccines. Parasite Immunol. 31:529538.
46. Pombo,, D. J.,, G. Lawrence,, C. Hirunpetcharat,, C. Rzepczyk,, M. Bryden,, N. Cloonan,, K. Anderson,, Y. Mahakunkijcharoen,, L. B. Martin,, D. Wilson,, S. Elliott,, D. P. Eisen,, J. B. Weinberg,, A. Saul,, and M.F. Good. 2002. Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet 360:610617.
47. Pradel, G. 2007. Proteins of the malaria parasite sexual stages: expression, function and potential for transmission blocking strategies. Parasitology 134:19111929.
48. Remarque, E. J.,, B.W. Faber,, C. H. Kocken,, and A. W Thomas. 2008. Apical membrane antigen 1: a malaria vaccine candidate in review. Trends Parasitol. 24:7484.
49. Richards, J. S.,, and J.G. Beeson. 2009. The future for blood-stage vaccines against malaria. Immunol. Cell Biol. 87:377390.
50. Rodrigues, M.,, R. S. Nussenzweig, and, F. Zavala. 1993. The relative contribution of antibodies, CD4+ and CD8+ T cells to sporozoite-induced protection against Malaria. Immunol. 80:15.
51. Rogerson, S. J.,, V. Mwapasa,, and S.R. Meshnick. 2007. Malaria in pregnancy: linking immunity and pathogenesis to prevention. Am. J. Trop. Med. Hyg. 77:1422.
52. Romero,, P.,, J.L. Maryanski,, G. Corradin,, R. S Nussenzweig,, V. Nussenzweig,, and F. Zavala. 1989. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature 341:323326.
53. Romero,, P. J.,, J.P. Tam,, D. Schlesinger,, P. Clavijo,, H. Gibson,, P. J. Barr,, R. S. Nussenzweig,, V. Nussenzweig,, and F. Zavala. 1988. Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei. Eur. J. Immunol. 18:19511957.
54. Rosenberg,, R.,, R.A. Wirtz,, D. E., Lanar, J., Sattabongkot,, T. Hall,, A. P Waters, and, C. Prasittisuk. 1989. Circumsporozoite protein heterogeneity in the human malaria parasite Plasmodium vivax. Science 245:973976.
55. Sagara, I.,, A. Dicko,, R.D. Ellis,, M. P. Fay,, S. I. Diawara,, M. H. Assadou,, M. S. Sissoko,, M. Kone,, A. I. Diallo,, R. Saye,, M. A. Guindo,, O. Kante,, M. B. Niambele,, K. Miura,, G. E. Mullen,, M. Pierce,, L. B. Martin,, A. Dolo,, D. A. Diallo,, O. K. Doumbo,, L. H. Miller, and, A. Saul. 2009. A randomized controlled phase 2 trial of the blood stage AMAl-C1/Alhydrogel malaria vaccine in children in Mali. Vaccine 27:30903098.
56. Schneider, J.,, S.C. Gilbert,, T.J. Blanchard,, T. Hanke,, K. J Robson,, C. M Hannan,, M. Becker,, R. Sinden,, G. L. L,, and A.V. Hill. 1998. Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nat. Med. 4:397402.
57. Schofield, L. 2007. Rational approaches to developing an antidisease vaccine against malaria. Microbes Infect. 9:784791.
58. Schofield, L.,, J. Villaquiran,, A. Ferreira,, H. Schellekens,, R. Nussenzweig, and, V. Nussenzweig. 1987. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature 330:664666.
59. Sedegah, M.,, M. Belmonte,, J.E. Epstein,, C. A. Siegrist,, W. R. Weiss,, T. R. Jones,, M. Lu,, D. J. J, and S.L. Hoffman. 2003. Successful induction of CD8+ T cell-dependent protection against malaria by sequential immunization with DNA and recombinant poxvirus of neonatal mice born to immune mothers. J. Immunol. 171:31483153.
60. Singh,, S., K. Miura,, H. Zhou,, O. Muratova,, B. Keegan,, A. Miles,, L. B Martin,, A. J Saul,, L. H. Miller, and, C. A. Long. 2006. Immunity to recombinant Plasmodium falciparum merozoite surface protein 1 (MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity. Infect. Immun. 74:45734580.
61. Sinnis, P., and, E. Nardin. 2002. Sporozoite antigens: biology and immunology of the circumsporozoite protein and thrombospondin-related anonymous protein. Chem, Immunol. 80:7096.
62. Spring, M. D.,, J.F. Cummings,, C. F. Ockenhouse,, S. Dutta,, R. Reidler,, E. Angov,, E. Bergmann-Leitner,, V. A. Stewart,, S. Bittner,, L. Juompan,, M. G. Kostepeter,, R. Nielsen,, U. Krzych,, E. Tierney,, L. A. Ware,, M. Dowler,, C. C. C,, R. W. Sauerwein,, S. J. de Vias,, O. Ofori-Anyinam,, D. E. Lanar,, J. L. Williams,, K. E. Kester,, K. Tucker,, M. Shi,, E. Malkin,, C. Long,, C. L. Diggs,, L. Soisson,, M. C. Dubois,, W. R. Ballou,, J. Cohen,, and D. G. Heppner, Jr. 2009. Phase 1/2 a study of the Malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A PLoS ONE 4:e5254.
63. Targett, G. A.,, and B.M. Greenwood. 2008. Malaria vaccines and their potential role in the elimination of malaria. Malar. J. 7:S10.
64. Tsuji, M.,, P. Romero,, R.S. Nussenzweig,, and F. Zavala. 1990. CD4+ cytolytic T cell clone confers protection against murine malaria. J. Exp. Med. 172:13531357.
65. Tuikue Ndam, N.,, and P. Deloron. 2008. Towards a vaccine against pregnancy-associated malaria. Parasite 15:515521.
66. Vanderberg, J., R. Nussenzweig,, and H. Most. 1968. Protective immunity produced by the injection of x-irradiate sporozoites of Plasmodium berghei. V. In vitro effects of immune serum on sporozoites. J. Parasitology 54:11751180.
67. Vekemans, J.,, and W.R. Ballou. 2008. Plasmodium falciparum. Malaria vaccines in development. Expert Rev. vaccines 7:223240.
68. Wu, Y.,, C. Przysiecki,, E. Flanagan,, S. N. Bello-Irizarry,, R. Ionescu,, O. Muratova,, G. Dobrescu,, L. Lambert,, D. Keister,, Y. Rippeon,, C. A. Long,, L. Shi,, M. Caulfield,, A. Shaw,, A. Saul,, J. Shiver,, and L.H. Miller. 2006. Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex. Proc. Natl. Acad. Sci. USA 103:1824318248.
69. Zavala,, F., M. Rodrigues,, D. Rodriguez,, J. R Rodriguez,, R. S. Nussenzweig, and, M. Esteban. 2001. A striking property of recombinant poxviruses: efficient inducers of in vivo expansion of primed CD8(+) T cells. Virology 280:155159.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error