All vaccines work in a similar way: by presenting foreign antigens to the immune system in order to activate a specific immune response . The aim of vaccination is usually to induce long-term protection through memory B cells [ 1 ]. The composition of vac cines can be diverse. Traditional formulations include live attenuated vaccines, which are composed of live viruses or bacteria that have been weakened in the laboratory to lower virulence by long- term passaging or genetic engineering (deletions in genes required for virulence) but are still able to activate the immune system. They elicit a strong response that can result in lifelong immunity with a minimum number of doses. Despite their advantages, live attenuated vaccines can have many drawbacks. Potential problems include difficulties with storage and transportation, where inappropriate handling may cause loss of vaccine efficacy. In addition, there are cases where this type of vaccine cannot be used (e.g., when patients take anti-infective drugs, or are immunocompromised for any rea son). There is a risk that attenuated vaccines can revert to a fully virulent pathogen (e.g., oral poliovirus vaccine [ 2 ]). Last but not least, the attenuation process itself is lengthy and depends on random events out of the control of the researchers (examples: BCG tuberculosis vaccine, yellow fever rotavirus vaccine) [ 3 , 4 ].

An alternative method is to inactivate the pathogens before use as a vaccine . This method is safer compared to the live attenuated vaccines, but is less potent in inducing immune response s. In short, such vaccines contain pathogens killed by heat or chemical treatment (i.e., formaldehyde). Risks related to such vaccines include errors in the inactivation. Because the inactivated pathogen does not reproduce in the host organism, there is a need for one or more “boosters,” i.e., administration of additional doses of the vaccine after defined intervals (examples: cholera vaccine , hepatitis A vaccine, rabies vaccine) [ 53 ].

With better biochemical and immunological methods avail able, it has been possible to engineer vaccine formulations by only using active antigens (rather than complete pathogens). This is referred to as a subunit vaccine . It uses only specific parts of a pathogen to immunize against disease. The search for such components is typically focused on surface-bound or secreted antigens, which provide the best accessibility for antibodies and other immune mechanisms [ 1 , 5 ]. Using purified proteins as a vaccine component is a widespread technique today. With bioinformatics, it is possible to select ideal antigen candidates for subunit vaccines, which have many advantages over the “whole-pathogen” approaches [ 6 ]. Subunit vaccine production is a safe process as it does not require the culturing of dangerous pathogens. The final product is also safer to use [ 7 , 8 ]: there is no infectious material, and thus no risk of the vaccine strain reverting to a harmful pathogen. In addition, it is possible to control all ingredients of the vaccine. Traditional vaccines induce very strong immunological responses with a very small dose; often this high response is not really necessary and does not always translate into later protection. In subunit vaccines, antigens are tested individually, and the kind of responses they provide are known. Thus, it is in principle possible to customize vaccines for specific patient groups (for example immunocompromised patients or patients already suffering from an infectious disease) [ 3].

References

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[1] Patronov A, Doytchinova I (2013) T-cell epi tope vaccine design by immunoinformatics. Open Biol 3:120139

 [2] Shimizu H, Thorley B, Paladin FJ et al (2004) Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001. J Virol 78:13512–13521

[3] Moyle PM (2015) Progress in vaccine development. Curr Protoc Microbiol 36:1–17

[4] Centers for Disease Control and Prevention (2012) Epidemiology and prevention of vaccine- preventable diseases. Public Health Foundation, Washington DC

[5] Plotkin S (2014) History of vaccination. Proc Natl Acad Sci U S A 2014:1–5

[6] Moyle PM, Toth I (2013) Modern subunit vaccines: development, components, and research opportunities. ChemMedChem 8:360–376

[7] Purcell AW, McCluskey J, Rossjohn J (2007) More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discov 6:404–414

 [8] Moyle PM, Toth I (2008) Self-adjuvanting lipopeptide vaccines. Curr Med Chem 15:506–516

مواضيع ذات صلة

Pan-Genomic Analysis

Reverse Vaccinology

Improving Vaccines over Natural Immune Responses

Selecting Vaccine Antigens

Principles of Vaccine Development

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