Prevention of diseases by vaccination is one of the most significant and cost-effective medical interventions at our disposal. Immunity is a result of coevolution between the immune system and pathogens. Microbes have evolved multiple strategies to evade, confuse, or inhibit the immune defence mechanism in order to proliferate in a biological shelter. The immune system must counter microbial invasions by eliciting protective immunity without inducing autoimmune disorders. Vaccination activates the protective immunity by mimicking a microbial invasion without the harmful, sometimes fatal, consequences of an infection.

Vaccination was first implemented on a wide scale more than 200 years ago with the introduction of the smallpox vaccine. Today, many infectious diseases caused by various viruses and bacteria can be prevented by vaccination with inactivated organisms, live attenuated organisms, or recombinant or partially purified components of the organisms. The host immune response after these vaccines is typically

Department of Molecular Genetics and Microbiology, Gene Therapy Center, University of Massachusetts Medical School, 381 Plantation Street, Suite 250, Worcester, MA 01605 USA e-mail: [email protected]

DOI 10.1007/978-1-4419-1207-7_14, © Springer Science+Business Media, LLC 2010

a robust induction of antibodies directed against antigens of the pathogen. Effective antibodies can neutralize or mediate killing of the organism, or inactivate toxins produced by the organism, thereby preventing infection or disease caused by infection. This antibody-directed approach has been successful either against the pathogens, whose antigens do not undergo antigenic variation, or against the pathogens, which undergo significant variability by frequently updated vaccines in order to match the circulating strains, such as influenza. In contrast, vaccines, which can effectively elicit the antigen-specific T-cell and B-cell immunities, are most likely required to protect host against pathogens which undergo rapid change in their antigenic structures (such as HIV and pathogens) and establish chronic infections, such as HCV and M. tuberculosis. While B-cell vaccine can prevent the host from the invasion of pathogens, T-cell vaccine can alter an ongoing immune response and consequently treat diseases. So far, few vaccine technologies have been successfully developed to induce protective T-cell responses in humans.

Classical vaccine strategies include the development of attenuated organisms, whole killed organisms, and protein subunits, followed by empirical optimization and iterative improvements. While these strategies have been remarkably successful for a wide variety of viruses and bacteria, these approaches have proven more limited for pathogens that require T-cell immune responses for their control. Largely because of technical advances in genome characterization, antigen identification, understanding the molecular bases of protective immune responses, and rational design of adjuvant and successful development of various delivery platforms, genetic vaccines consisting only of DNA as plasmids and recombinant subunit vaccines delivered by replicating and non-replicating viral vectors for complex organisms have been accelerated in the past decade. The skeletal muscle is a clinically accepted target for vaccination and its stable post-mitotic nature allows the use of both viral and non-viral vectors to induce the antigen-specific humoral and cellular immunity.

In this chapter, we will review the progress of muscle as a target for DNA vaccines and for recombinant subunit vaccines based on adenoviral and adeno-associated viral vectors. In the end, we will summarize these vaccine strategies in the context of HIV vaccine developments.

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