Vaccines are highly effective in the prevention of certain life-threatening infectious diseases. However, immunological drugs are difficult to produce. They require a great deal of rigor and often a lot of time. How are vaccines made and what are the major development stages? We provide some answers.
Vaccines, a crucial weapon to prevent infectious diseases
Vaccination prevents 2 to 3 million deaths worldwide each year.1 Vaccines are critical to the prevention and control of infectious diseases. Classed as immunological medicinal products by the European regulations, they significantly reduce complications and mortality rates following exposure to an infectious agent.2 However, it often takes a long time to produce a vaccine, with numerous stages along the way before it can be made available, to ensure maximum efficacy and safety.
There are three types of vaccines on the market: inactivated vaccines, such as those for tetanus and whooping cough, attenuated ones, like those for Dengue fever, TB or shingles, and vectorized ones, such as certain recent vaccines against Covid-19. These vaccines make it possible to inactivate, attenuate or vectorize the virus.
Generally speaking, whatever the type of vaccine, the manufacturing approach is almost always the same, with the first step being to build up a bank of microorganisms (viruses, bacteria or parasites), without mutations. This is followed by culturing of the microorganisms and harvesting of the antigen, then purification and concentration of the substance produced, along with its inactivation if necessary, and, finally, production of antigen valencies. Once these steps have been completed, the vaccine is put into pharmaceutical form and packaged, with the combination of valencies, and the addition of adjuvants and stabilizers if necessary, and placed in vials. For every new vaccine, each batch undergoes quality control by the French National Agency for Medicines and Health Products Safety (ANSM) before being put on the European market.
The vaccine development process
As is the case for any drug, vaccine development is governed by European recommendations and can be a very long process, taking up to 14 years or more in some cases.
The preclinical development phase is the first step in the vaccine research process, before studies can begin in humans. In particular, this phase aims to determine the safety of the vaccine, its tolerability and its pathogenicity. Once this first phase has been validated, and following the authorization of the ANSM and Ethics Committee approval, clinical trials can then begin in humans. Trials are sequenced into four phases, with phase I concerning a small group of healthy volunteers to assess the safety and immunogenicity of the vaccine. This is followed by phase II trials in the population for whom the vaccine is recommended in order to assess safety and study the vaccination schedule. Phase III concerns a larger population and includes several thousand people. And finally, phase IV is conducted after the vaccine is marketed and is intended, in particular, to assess the efficacy of the vaccine and verify the absence of long-term side effects3
So making a vaccine is a very slow process that can take several years. However, faced with the emergence of new pathogens, research aims to accelerate the development of new vaccines, in particular RNA and DNA vaccines that will enable the production of antigens directly within cells, in order to mimic viral infection and potentiate the immune response. 4
Types of vaccines available against Covid-19
In the past year, four different types of Covid-19 vaccines have been developed or are under development around the world. First, the virus vaccines; they are either attenuated or inactivated. Second, the viral vector vaccines; they can either be replicating or non-replicating. Other pathogenic virus such as adenoviruses are used, they do not infect human being. Third, there are the coronavirus protein vaccines. And finally, the genetic material vaccines, either DNA or mRNA, which is a recent innovation of the history of vaccine research.
Lelièvre JD. Les vaccins de demain [Vaccine of the future]. Rev Francoph Lab. 2019 May;2019(512):52-63. French. doi: 10.1016/S1773-035X(19)30258-8. Epub 2019 Apr 24. PMID: 32518603; PMCID: PMC7270526.