VACCINE DEVELOPMENT: HISTORICAL ANALYSIS AND HOW TO ACCELERATE

Abstract

Vaccines proved to have great impact in public health as they exert primary prevention level in preventive medicine. Their implementation resulted in the eradication of smallpox, near eradication of polio, control of several infectious diseases as well as prevention of millions of deaths each year. They are one of the most effective public health measures available in case of infectious disease. Vaccines development started as early as the end of the 18thcenturyby Edward Jenner who used cowpox-infected materials to immunize against smallpox and introduced the term “vaccine”. Louis Pasteur refined Jenner’s work and introduced the basic principles of vaccination represented by pathogen isolation, inactivation/attenuation and injection. The introduction of cell culture for virus propagation enabled the development of methods for attenuating viral vaccines resulting in a golden age of first vaccines development that occurred in the second half of the 20thcentury and licensure of vaccines against polio, measles, mumps, rubella and varicella. Vaccines developed by inactivation/attenuation of infectious agents are termed conventional/traditional vaccines. The second renaissance of vaccine development was introduced by the development of subunit vaccines for which only parts (protein/peptide, carbohydrate antigens) of target pathogens are used to induce appropriate immune responses. The targeted subunit has to be abundant and conserved in the pathogen, recognized by the immune system and able to elicit a protective immune response. The antigenic part of a subunit vaccine can be prepared by either isolating a specific component from the pathogen or synthesis of specific protein by molecular genetic techniques. This allowed the development and licensure of vaccines against Haemophilus influenza type B;Meningococcus A, C, W, and Y; Pneumococcus; as well as the introduction of acellular pertussis vaccine, hepatitis B surface antigen (HBsAg) and bivalent or quadrivalent human papilloma virus (HPV)vaccine. The latest renaissance in vaccine development was started to develop vaccines that induce protective immunity beyond the mechanisms evolved by nature against pathogens exhibiting hyper variability (influenza, dengue, HIV-1, HCV), their conventional vaccines exacerbate disease (RSV, dengue) or those leading to persistent/latent infection or have an intracellular phase such as (HIV-1, hepatitis C virus (HCV), cytomegalovirus (CMV), herpes simplex and Mycobacterium tuberculosis and malaria as well as emerging pathogens. New technologies have to be developed for next generation vaccines development against pathogens that fail to induce sterilizing immunity as well as currently emerging ones. These technologies can be divided into three major categories related to antigen discovery, adjuvants and vaccine delivery, and deciphering human immune respo