Antigen delivery is a major concern in design and development of new generation vaccines to achieving protection against lethal pathogens. Conventional ways of antigen delivery associated with limitations of multiple doses requirement, cost factor, inappropriate activation of immune system and toxicities are the major cause of concern. Under this, state of affairs polymers as nanovehicles have shown promising marks and thus maintain long lasting immune responses to the antigens. Polymers are biocompatible, biodegradable and do not cause any significant localized and systemic toxicities. Due to their biodegradation nature, they clear off from the body by phagocytes and maintain tissue homeostasis. Due to their small size, they can easily cross different biological barriers and deliver the antigen effectively. In this chapter, we have underlined the current research emphasizing on the nanoscale features, its course through the past and the future perspectives focusing on the current needs. If successful, these nano gaints would be no surprise near future.
TopIntroduction
Foremost objective of vaccination is activation of immune response to achieve long term protection against microbial pathogens. For a successful vaccine, efficacy, biocompatibility, cost factor and production at large level are the major desires. Vaccines significantly reduced the rate of morbidity and mortality from the diseases such as small pox, polio, tetanus, pertussis, mumps, rubella, diphtheria, and yellow fever, thus improved human life style. However, there is no promising vaccines available against human immunodeficiency virus (HIV), malaria, hepatitis, and dengue fever diseases. Major hurdles in their development are antigenic variability, lack of appropriate animal models for disease understanding, genomic instability and poor antigen delivery system. Other factors include scarcity of funds and long waiting time taking in clinical trials (Shakya & K.S. 2014). Out of several, delivery of antigen is a major and considerable factor at research level. Generally, delivery in conventional vaccines achieve by metallic salts such as Aluminium hydroxides and sulphates commonly known as Alum compounds. They work on principle of precipitation, for long and sustain release of the antigen. Sometimes, immunomodulators can also use in these delivery systems to achieve effective immune responses (Ryan et al. 2001). Immunomodulators activate the immune system toward Th1/Th2 pathway. Moreover, acute and chronic tissue toxicities are associated with these delivery systems. In this sense, it is critical to design immunological inert and biocompatible vehicle for vaccine delivery.
Last few decades, research focus has been shifted towards development of polymeric nanocarriers for antigen delivery. NPs can encapsulate good amount of antigen and protects them from in vivo degradation. Antigen with NPs presented in similar ways as presented by pathogens in conventional vaccines. Due to their nano size, NPs can easily endocytose by antigen presenting cells (APCs) either through direct phagocytosis or receptor mediated endocytosis. APCs processed Ag and presented in form of peptides for activation of Th cells. Th cells further activate other Th and Tc cells (Figure 1). Th cells leads to activation of B cells or plasma cells to secrete antibodies against the antigen and protects from pathogens. Efficacy of polymeric NPs already has been established in different studies. They are promising tool for antigen delivery and achieving protective immune response. In this sense, current chapter describes different types of polymeric NPs and their efficacy for activation of immune system.
Figure 1.
Schematic representation of immune system dependency on particle size; particles less than 200 nm endocytose by APCs and activate cytotoxic T cells, while particles larger than 200 nm activate naïve Th cells, which further activate effector T and B cells.