Faculty

Fidel Zavala, MD

"Working in the Malaria Research Institute is tremendously exciting. It provides the setting for enormous cross-fertilization of ideas, as well as new technical capabilities that will greatly facilitate and advance our research in malaria."

The Zavala lab's current research focuses on the characterization of the cellular and molecular mechanisms underlying the induction of protective T-cell-mediated immunity against malaria parasites. The researchers generated strains of transgenic mice bearing T cell receptors specific for parasite antigens recognized by CD8+ or CD4+ T cells. Using these mice, they are currently conducting studies to characterize the molecular and genetic events involved in the development and maintenance of effector anti-parasite T cells, and to find out how CD4+ /CD8+ T cells interact during the development of immunity against infection. Their research combines in vivo immunophysiology studies with molecular and genetic approaches. Particular emphasis is given to research aimed at characterizing the mechanisms involved in tissue-trafficking of activated CD8+ T cells and identifying the nature of the molecular processes leading to the development of memory subsets.

These studies, which use a rodent parasite system, provide the rationale and experimental basis for research aimed at developing an antimalaria vaccine for humans. Furthermore, these rodent models are excellent systems for studying the general principles of protective immunity against intracellular pathogens, as they develop in vivo. These studies enhance our understanding of the immune system at the most fundamental level.

CONTACT

Johns Hopkins Bloomberg School of Public Health
615 N. Wolfe Street
Room E3630
Baltimore, MD 21205

email:    fzavala@jhsph.edu
phone:   443-287-1769
fax:        410-955-0105

LINKS

JHSPH Faculty Page

SELECTED PUBLICATIONS

Hafalla JCR, Rai, U., Bernal- D., Rodriguez A and Zavala F. 2007 Efficient development of Plasmodium liver stage-specific memory CD8+ T cells during the course of blood stage malaria infection. J. Infect. Diseases (in press)

Melendi GA, Zavala F, Bucholz UJ, Boivin G, Collins PL, Kleeberger S, Polack FP. 2007 Mapping and characterization of the primary and anamnestic H-2d restricted cytotoxic T lymphocyte response in mice against human metapneumovirus. J Virol. Aug 1; [Epub ahead of print]

Cockburn I A and Zavala F. 2007 T cell memory in malaria Curr. Opin. Immunol. 19:1-6

Pinheiro A , Morrot, A., Chakravarty S., Overstreet, M., Bream,JH., Irusta, PM.,and Zavala F. 2007 IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells J. Leuk. Biol 81-1102-10

Li S, Locke E, Bruder J, Clarke D, Doolan DL, Havenga MJ, Hill AV, Liljestrom P, Monath TP, Naim HY, Ockenhouse C, Tang DC, Van Kampen KR, Viret JF, Zavala F, Dubovsky F. 2007 Viral vectors for malaria vaccine development. Vaccine. 25:2567-74

Kumar K A, Sano GI, Boscardin S, Nussenzweig RS, Nussenzweig MC, Zavala F and Nussenzweig V.2006 The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. Nature 444 (7121):937-40

Hafalla JC, Urvashi Rai, Alexandre Morrot, Dabeiba Bernal-Rubio, Fidel Zavala and Ana Rodriguez. 2006 Priming of CD8+ T cell responses following immunization with heat-killed Plasmodium sporozoites. Eur. J Immunol 36:1179-86.

Morrot A, Ian A. Cockburn, Michael Overstreet, Dolores Rodríguez and Fidel Zavala. 2006. Protective CD8+ T cells induced by malaria sporozoites do not undergo modulation of IL-7 receptor expression. Infect. Immun. 74: 2495-2497

Boscardin AB, Hafalla JCR, Masilamani RF, Kamphorst, AO, Zebroski, HA Rai U, Morrot A, Zavala F, Steinman RM, Nussenzweig, RS and Nussenzweig MC. 2006. Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses. J. Exp. Med. 203: 599-606

Hafalla JC, Cockburn IA, and Zavala F. 2006. Protective and Pathogenic roles of CD8+ T cells during malaria infection. Parasite Immunol. 28:15-24

Morrot A, Hafalla JC, Cockburn IA, Carvalho LH, Zavala F. IL-4 receptor expression on CD8+ T cell is required for the development of protective memory responses against liver stages of malaria parasites. J Exp Med. 202(4):551-60, 2005. Article

del Portillo HA, Lanzer M, Rodriguez-Malaga S, Zavala F, Fernandez-Becerra C. Variant genes and the spleen in Plasmodium vivax malaria. Int J Parasitol 34:1547-1554, 2004. Abstract

Morrot A, Zavala F. Regulation of the CD8+ T cell responses against Plasmodium liver stages in mice. Int J Parasitol 34:1529-1534, 2004. Abstract

Morrot A, Zavala F. Effector and memory CD8+ T cells as seen in immunity to malaria. Immunol Rev 201:291-303, 2004. Abstract

Tongren JE, Zavala F, Roos DS, Riley EM. Malaria vaccines: if at first you don't succeed... Trends Parasitol 20:604-610, 2004. Abstract

Hafalla JC, Morrot A, Sano G, Milon G, Lafaille J, Zavala F. Early self-regulatory mechanisms control the magnitude of CD8+ T cell responses against liver stages of murine malaria. J Immunol 171:964-970, 2003. Article

Tsuji M and Zavala F. T cells as mediators of protective immunity against the liver stages of Plasmodium. Trends Parasitol 19:88-93, 2003. Abstract

Carvalho LH, Sano G,Hafalla JC, Morrot A, Curotto M, Zavala F. IL-4 secreting CD4+ T cells are crucial to the development of CD8+ T cell responses against malaria liver stages. Nature Med 8(2):166-170, 2002. Abstract

Hafalla JC, Sano G, Carvalho L, Morrrot A, Zavala F. Short-term antigen presentation and single clonal burst limit the magnitude of the CD8+ T cell responses against malaria liver stages. Proc Natl Acad Sci (USA) 99:11819-11824, 2002. Article

Jung S, Unutmaz D, Wong DP, Sano GI, De los Santos K, Sparwasser T, Wu S, Zavala F, Pamer EG, Littman DR, Lang R. Abrogation of cytotoxic T cell cross priming by induced in vivo ablation of CD11c+ dendritic cells. Immunity 17:211-220, 2002. Abstract

Bruna-Romero OB, Hafalla JC, Gonzales G, Sano, G, Tsuji M, Zavala F. Detection of malaria liver stages in mice infected through the bite of a single Anopheles mosquito using a highly sensitive real-time PCR. Int J Parasitol 31:1499-1502, 2001. Abstract

Sano G, Hafalla JC, Abe R, Lafaille J, Zavala F. Swift development of protective effector functions in naïve CD8+ T cells against malaria liver stages. J Exp Med 194:173-179, 2001. Article

Tsuji M and Zavala F. Peptide-based vaccines to induce protective antibody and T-cell mediated immunity against liver stages of malaria. Mol Immnunol 38:433-442, 2001. Abstract

Zavala F, Rodrigues M, Rodriguez D, Rodriguez JR, Nussenzweig RS, Esteban M. A striking property of recombinant poxviruses: efficient inducers of in vivo expansion of primed CD8+ T cells. Virology 280:55-159, 2001.

Ferreira J, Myahira Y, Roriguez JR, Rodriguez D, Nussenzweig RS, Esteban M, Zavala F. Immunogenicity of Ty-VLP bearing a CD8+ T cell epitope of the CS protein of P. yoelii: Enhanced memory response by boosting with recombinant vaccinia virus. Vaccine 18:1863-1869, 2000. Abstract