During the interaction with an infectious agent, the immune system develops and optimizes an effective defense strategy that pre vents further spread of the pathogen , interrupts its life cycle, and eventually eliminates it from the body. Thereafter, the affected individual ideally acquires protective immunity that prevents the recurrence of an infection by the same agent in the future. In order to provide protection from infectious diseases vaccines have to be designed to induce immune response s comparable to the natural occurring immune response against an infectious agent. However, there is a significant difference between the expected effects of vac cines and those that are attributed to infectious agents. While it is common knowledge that infections are usually associated with clinical symptoms of disease, such a coincidence generally is not acceptable for the use of vaccines.

Symptoms of an infection are either caused directly by the pathogen , or, more often, they are consequences of the emerging immune response , representing side effects of our physiological defense mechanisms. Typical complaints such as physical discom fort, malaise, fever, or organ malfunction in most cases are related to inflammatory reactions that occur in course of the immunological defense process. Since vaccines are administered to prevent infections and/or diseases, they are expected to provide protection without the risk of side effects or clinical symptoms of disease. To this end in vaccine development it is important to understand the life cycle of an infectious agent, how it multiplies and infests the human organism, and how the immune system counteracts and overcomes the microbial invasion and finally builds up a protective immunity, i.e., an effective barrier against future challenges by the same agent. Moreover, it is essential to defi ne which elements of the natural immune response are relevant for the elimination of the pathogen and future protection, and which are responsible for symptoms of disease and discomfort. Ideally, a vaccine should induce only the elements of the natural immune response that are essential for protection, but simultaneously exclude all negative effects of natural infection. In vaccine development, therefore, not only the elements of the immune response guaranteeing best protection must be considered, but also the acceptable tolerability and safety ramifications of the induced inflammatory response. As a consequence the design of a vaccine has to be based on both structural and biological properties/qualities of an infectious agent as well as the type and quality of naturally occurring immune responses initiated by the infectious pathogen.

Initially vaccine development focused on the steps required to elicit activation of a protective immunity and generation of immunological memory by virtually mimicking the interaction of an infectious agent with the human immune system without posing any risks of the infectious disease to the vaccinee. This requires the identification of antigenic structures relevant for protection as well as definition of immune response mechanisms adequate to elicit protective immunity. The latter will vary according to specific disease (Table 1 ). While for many decades vaccine development concentrated primarily on targeting components of the adaptive immunity (B cells or immunoglobulins, T cells, and cytokines, such as interferon), recent research indicates that innate and adaptive immunity have to interact vigorously to initiate the most potent type of protective immune response [ 1 ]. In particular, antigen processing and presentation by DCs are key steps in the development of efficient immune responses. The recognition of the important role of innate immunity in controlling the adaptive response (Figure 1 ) has led to a reappraisal of the role of adjuvants in vaccinology [ 1 ].

Table1. Quality of protective immune response s to infection differs according to type of disease.

Fig1. Role of adjuvants in vaccinology. Adapted from Guy B: The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol. 2007 Jul;5(7):505–17

In most instances, vaccines are developed to protect human beings from infectious diseases on a population-based level. This implies that vaccines should provide protection for basically every vaccinated individual within an immunogenetically heterogeneous population. Conventional vaccines formulated with whole microbial pathogens usually provide a broad range of different antigens and antigenic epitopes that in most instances guarantee sufficient immunostimulatory activity for a heterogeneous population. In contrast, highly purified antigens consisting only of a limited number of epitopes may pose the risk of insufficient interaction with individuals missing the adequate immune receptor repertoire. Moreover, genetic heterogeneity of the pathogen may counteract the expected benefit of highly purified vaccine antigens. Keeping this in mind, selection of vaccine antigens has to balance specificity and purity of antigens against sufficient antigenic variety to ensure targeting the immune system of every or at least the majority of individuals in a given population.

References
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[1] Moser M, Leo O (2010) Key concepts in immunology. Vaccine 28 Suppl 3:C2–C13

مواضيع ذات صلة

Selecting Vaccine Antigens

A Brief History of Vaccination

Development of Vaccines for Tuberculosis and Meningitis

Development of Vaccines for Viral Hepatitis, Coronavirus, and Norovirus

Development of Powerful Influenza Vaccines

Vaccines for HIV and Ebola Virus

Vaccines for Diseases Associated with Urban Areas in the Developing Countries

HIV Vaccine

Yellow Fever Vaccine

Tuberculosis Vaccine

Rotavirus Vaccines

Pertussis Vaccines