TITLE

Protracted Sterile Protection with Plasmodium yoelii Pre-erythrocytic Genetically Attenuated Parasite Malaria Vaccines Is Independent of Significant Liver-Stage Persistence and Is Mediated by CD8+ T Cells

AUTHOR(S)
Tarun, Alice S.; Dumpit, Ronald F.; Camargo, Nelly; Labaied, Mehdi; Pu Liu; Takagi, Akihide; Ruobing Wang; Kappe, Stefan H. I.
PUB. DATE
August 2007
SOURCE
Journal of Infectious Diseases;8/15/2007, Vol. 196 Issue 4, p608
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Irradiation-attenuated sporozoite vaccinations confer sterile protection against malaria infection in animal models and humans. Persistent, nonreplicating parasite forms in the liver are presumably necessary for the maintenance of sterile immunity. A novel vaccine approach uses genetically attenuated parasites (GAPs) that undergo arrested development during liver infection. The fate of GAPs after immunization, their persistence in vaccinated animals, and the immune mechanisms that mediate protection are unknown. To examine the developmental defects of genetically attenuated liver stages in vivo, we created deletions of the UIS3 and UIS4 loci in the Plasmodium yoelii rodent malaria model (Pyuis3[–] and Pyuis4[–]). The low 50% infectious dose of P. yoelii in BALB/c mice provides the most sensitive infectivity model. We show that P. yoelii GAPs reach the liver, invade hepatocytes, and develop a parasitophorous vacuole but do not significantly persist 40 h after infection. A single dose of Pyuis4(–) sporozoites conferred complete protection, but full protection by Pyuis3(–) sporozoites required at least 2 immunizations. CD8+ T cells were essential for protection, but CD4+ T cells were not. Our results show that genetically distinct GAPs confer different degrees of protective efficacy and that live vaccine persistence in the liver is not necessary to sustain long-lasting protection. These findings have important implications for the development of a P. falciparum GAP malaria vaccine.
ACCESSION #
26449978

 

Related Articles

  • Nanoparticles modify dendritic cell homeostasis and induce non-specific effects on immunity to malaria. Xiang, Sue D.; Kong, Ying Y.; Hanley, Jennifer; Fuchsberger, Martina; Crimeen-Irwin, Blessing; Plebanski, Magdalena // Transactions of the Royal Society of Tropical Medicine & Hygiene;Jan2015, Vol. 109 Issue 1, p70 

    Background Many current vaccines to a specific pathogen influence responses to other pathogens in a process called heterologous immunity. We propose that their particulate nature contributes to non-specific effects. Herein, we demonstrate polystyrene nanoparticles modulate dendritic cell (DC)...

  • Malaria Vaccine Development: Progress and Challenges. Reed, Z. H.; Friede, M.; Kieny, M. P. // Current Molecular Medicine;Mar2006, Vol. 6 Issue 2, p231 

    A safe and effective malaria vaccine would contribute greatly to the control and prevention of the disease. Although a review of global activity in malaria vaccine development does reflect significant activity, progress has remained slow. This article discusses the current vaccine candidates,...

  • Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-centre trial of the RTS,S/AS01 malaria vaccine in African children.  // Malaria Journal;2011, Vol. 10 Issue 1, p222 

    The article discusses a study which evaluated vaccine efficacy in a phase III multi-centre trial of the RTS, S/AS01 malaria vaccine in African children. The study described the methods used to estimate efficacy of the primary course of vaccination, and of a booster dose, in preventing clinical...

  • A Malaria Vaccine Based on the Polymorphic Block 2 Region of MSP-1 that Elicits a Broad Serotype-Spanning Immune Response. Cowan, Graeme J. M.; Creasey, Alison M.; Dhanasarnsombut, Kelwalin; Thomas, Alan W.; Remarque, Edmond J.; Cavanagh, David R. // PLoS ONE;2011, Vol. 6 Issue 10, p1 

    Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed,...

  • Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy. Leitner, Wolfgang W.; Bergmann-Leitner, Elke S.; Angov, Evelina // Malaria Journal;2010, Vol. 9, p145 

    Background: The immunological mechanisms responsible for protection against malaria infection vary among Plasmodium species, host species and the developmental stage of parasite, and are poorly understood. A challenge with live parasites is the most relevant approach to testing the efficacy of...

  • Development of behaviour change communication strategy for a vaccination-linked malaria control tool in southern Tanzania. Mushi, Adiel K.; Schellenberg, Joanna; Mrisho, Mwifadhi; Manzi, Fatuma; Mbuya, Conrad; Mponda, Haji; Mshinda, Hassan; Tanner, Marcel; Alonso, Pedro; Pool, Robert; Schellenberg, David // Malaria Journal;2008, Vol. 7, Special section p1 

    Background: Intermittent preventive treatment of malaria in infants (IPTi) using sulphadoxine-pyrimethamine and linked to the expanded programme on immunization (EPI) is a promising strategy for malaria control in young children. As evidence grows on the efficacy of IPTi as public health...

  • Vaccine Efficacy against Malaria by the Combination of Porcine Parvovirus-Like Particles and Vaccinia Virus Vectors Expressing CS of Plasmodium. Rodríguez, Dolores; González-Aseguinolaza, Gloria; Rodríguez, Juan R.; Vijayan, Aneesh; Gherardi, Magdalena; Rueda, Paloma; Casal, J. Ignacio; Esteban, Mariano // PLoS ONE;Apr2012, Vol. 7 Issue 4, p1 

    With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvoviruslike particles (PPV-VLPs) carrying the CD8+ T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein...

  • Evidence of Blood Stage Efficacy with a Virosomal Malaria Vaccine in a Phase IIa Clinical Trial. Thompson, Fiona M.; Porter, David W.; Okitsu, Shinji L.; Westerfeld, Nicole; Vogel, Denise; Todryk, Stephen; Poulton, Ian; Correa, Simon; Hutchings, Claire; Berthoud, Tamara; Dunachie, Susanna; Andrews, Laura; Williams, Jack L.; Sinden, Robert; Gilbert, Sarah C.; Pluschke, Gerd; Zurbriggen, Rinaldo; Hill, Adrian V. S. // PLoS ONE;2008, Vol. 3 Issue 1, p1 

    Background. Previous research indicates that a combination vaccine targeting different stages of the malaria life cycle is likely to provide the most effective malaria vaccine. This trial was the first to combine two existing vaccination strategies to produce a vaccine that induces immune...

  • TRAVEL ADVICE MALARIA.  // GP: General Practitioner;6/23/2003, p83 

    Focuses on immunization against malaria in various countries of the world. Drugs used for immunization; Dosage of drugs used.

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics