Abstract

Among the numerous infectious diseases, malaria still remains the main cause of morbidity and mortality across the world. Every year more than 200 million cases are registered and death toll is of around 4,00,000. The emergence of insecticide and drug resistance has surged an alarming situation to find an effective means to tackle it. From various approaches used for reducing the damage created by malaria to the society, developing effective vaccine has gained the attention of scientific community. The large genome size (24 MB), heterogeneity of the genes, complex life cycle in two different hosts, and expression of wide range of these genes are claimed to hinder the malaria vaccine development. It requires good understanding of the host-pathogen interaction and its correlation with the sterile protection. Recently, subunit vaccine have shown certain promising responses; however, the currently in use of RTS,S vaccine has failed to generate the long-term sterile protection as well as effector memory CD8+T cells. However, the success of sterile protection through vaccination has been proven long back by experimental approaches, where it could be achieved using irradiated sporozoites (RAS) in rodents and humans. Similarly, GAP (genetically attenuated parasite) and CPS (chloroquine chemoprophylaxis with Plasmodium sporozoites) have been shown to induce sterile immunity. Despite all the developments, generation of species and stage specific-CD8+ T cell responses has been modest. In order to generate long-lasting immune response, particularly, liver-stage specific-CD8+ T cells, it is indeed required to study the CD8+ T cell epitope repertoire and its implications on the host immune system. In this chapter we will discuss the current status of T cell-based vaccines and the challenges associated with it.

Highlights

  • Malaria pathogenesisSince the origin of Homo sapience through the continuous evolution process, we have become the most successful creature on the Earth by maintaining the symbiotic relation with other species to live freely

  • The selection of circumsporozoite protein (CSP) Ag in RTS,S vaccine is derived from the earlier reports where approach of inactivated sporozoites has generated sterile protection and provoked immune response which was mediated by CSP-specific Abs and cell mediated immunity (CMI)

  • Despite the advancement in the field of technology, drug and insecticide resistance followed by recent threat of delayed clearance of parasite against the frontline of antimalarial(s) have created herculean situation

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Summary

Introduction

Since the origin of Homo sapience through the continuous evolution process, we have become the most successful creature on the Earth by maintaining the symbiotic relation with other species to live freely. The cycle begins with the bite of infected female Anopheles mosquitoes to the human during the blood meal and transfers sporozoites [12] into the skin. They remain at the inoculation site for a short time and further travel to the liver where they invade the liver hepatocytes. These schizonts rupture and release merozoites which come out and infect the erythrocytes (RBCs). Once the merozoites pop-up in the blood stream, they infect the RBCs which further divide, replicate and passes through several developmental stages, ring stage-trophozoite stage-schizont formation in chronological order, and ended up in release of countless merozoites These merozoites further infect the new RBCs and cycle continues.

Malaria elimination and eradication
Approach of vaccine development: A ray of hope
History of malaria vaccine development
RTS,S malaria vaccine: Learning lessons from gained knowledge
Whole sporozoite vaccines
Chemo- prophylaxis and sporozoites (CPS)
Radiation attenuated sporozoites (RAS)
Genetically attenuated sporozoites (GAS)
T-cell based immune response: A key player of vaccine development
T-cell response
T-cell and their subtypes
T cells and vaccine development
Findings
Conclusion
Full Text
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