Sarat K. Dalai

By Vishakha Bhurani and Sarat Kumar Dalai

Cytokines are low molecular weight proteins having roles in essential biological processes, particularly for the immune system. As they have a key role to play, an abnormality in their function can lead to wide variety of diseases (clinical consequences). Thus using the cytokines as therapeutic targets has been an area of active research. Of the entire family, we would like to shed light on two major ones IL-10 and IL-12 having an array of roles in cellular response to infection and autoimmunity. IL-12 is a pro-inflammatory cytokine that has been shown to enhance IFN-γ producing T cell responses and has been widely tested as a vaccine adjuvant. Many studies have shown that IL-12 acts as a link between innate and adaptive immunity by inducing IFN-γ production and polarizing naive CD4 T cells to become Th1 cells. It also has roles in CD8 T cell differentiation. On the other hand, IL-10 is an anti-inflammatory cytokine and has role in maturation of memory CD8 T-cell. It also plays a critical role in preventing autoimmunity and also limits tissue injury by interfering with the intensity and duration of immune response. We would thus like to discuss in details about the therapeutic use of these cytokines for infections as well as diseases such as cancer, autoimmune disorders etc.

Part of the book: Immunoregulatory Aspects of Immunotherapy

By Nikunj Tandel, Devang Trivedi, Aditi Mohan Krishnan and Sarat Kumar Dalai

Among the numerous infectious diseases, malaria remains a major health challenge. Despite the various approaches adopted for the vector control and availability of antimalarial drugs, the success of malaria eradication is dampened by the spread of drug and insecticide resistance, unavailability of proper diagnostic treatment and successful vaccine. Among the various approaches, vaccination with the aim of developing protective immunity is the most suited, safe and reliable approach for the entire mankind. Numerous approaches are in use for vaccine development; however, they suffer from the drawbacks that immunity developed is short lived and are both species- and stage-specific. Of late, radiation sterilization has drawn the attention in the vaccine development due to its advantages over the conventional methods, and successful clinical trials of irradiated vaccines against the pathogens and tumor. Recently, a novel approach of genetically attenuated sporozoites (PfRAS, PfSPZ, PFSPZ-GA1 sporozoites vaccines) has shown promising results by generating protective immunity against the homologous and heterogenous infection in the clinical trials. Radiation techniques have also been beneficial in controlling the insects by sterility technique. In this chapter, we have recapitulated the role of radiation biology in the malaria vaccine development with its current status and future challenges associated with the development of radiation attenuated parasite vaccine.

Part of the book: Ionizing and Non-ionizing Radiation

By Nikunj Tandel and Sarat K. Dalai

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.

Part of the book: Current Topics and Emerging Issues in Malaria Elimination