Due to the fast-spreading as well as the constantly-mutating nature of the COVID-19 virus, the need for vaccines is urgent. The production of the vaccine is now progressing at a significant pace, with some available to be administered. The Indian Government has specified free vaccination against COVID-19 for individuals aged 45 and above. Before a vaccine comes to the market a.k.a. at its phase IV level, it has to undergo a rigid and vigilant process in order to be approved along with a set of emergency use authorization guidelines which are implemented during the time of fast-acting diseases.
Although the production and manufacture can vary from one vaccine to another, the development process remains similar throughout. According to Central Drugs Standard Control Organization, India (CDSCO) as of September 2020, the criteria for selecting the vaccines is done based on the following parameters:
- Toxicity data: If the vaccines cause any kind of local or systemic inflammation, it has to be recorded in the toxicity data. Even if the vaccine alone does not cause any of these cross-reactions, the adjuvants used to enhance the action of the vaccine or if the vectors employed can trigger some kind of an unwarranted inflammation. Haematology studies, histopathological examinations, serum chemistry analyses and sometimes even clotting parameters are assessed in order to determine the toxicity data.
- Pharmacokinetic studies: These are the non-clinical safety studies usually done on the required adjuvants, preservatives, and vaccine transport formulations, all of which can affect the uptake and activity of the vaccine. Different routes of administration (e.g. intranasal, oral, intradermal, rectal and intravaginal routes) can also affect the potency, immunogenicity, tolerability, and long term safety, all of which have to be examined and addressed.
- Animal models and doses: These are the pre-development processes employed in order to determine the dose of antigen required to garner the possible immunogenic response, from which the expected outcomes are formulated. For vaccines administered by alternative routes, the anatomy and physiology of the chosen animal model should be considered. Rabbits and Dogs respond well to intranasal administration whereas mice and rats are better suited for intravenous and intradermal routes.
- First in Human(FIH) Trials: After obtaining the initial results and reference points from the animal models, vaccines are now ready for FIH trials. All the assays to be done should be specified before the clinical trials begin. Vaccine trials in humans are divided into three phases. Phase I is where the vaccine is injected into healthy individuals. Phase II is conducted in individuals who represent the intended target patient for the vaccine. Phase III is done to check the efficacy and safety of the vaccine based on the immunological reactions to protect against clinical disease. Phase IV is the post-marketing trials after which the vaccines are available in the market. A comprehensive trial report should be compiled recording all the data including the pre-vaccination requirements.
- Immunogenic assessments: For a vaccine to work, it should garner an immune response when injected into a healthy individual (Phase I clinical trials). An Immune Correlate of Protection (ICP) is a set of possible immune responses(humoral as well as cell-mediated) for vaccine-induced protection against pathogens. The humoral immune response includes the serum antibody titer levels and the types of antibodies produced post vaccination. The dose of antigen at which the highest number of antibodies are produced is considered for vaccination. Cell-mediated immune response consists of the number of sensitized T-cells and the levels of cytokines in the blood, post vaccination.
- End points: The vaccine should be made up of different kinds of antigens in order to protect against various subtypes of the organisms and the humoral immune response obtained should be of the anamnestic(memory) type. The antibody levels in the vaccinated individuals should be similar to the standards laid out in the correlating ICP.
- Special consideration for COVID-19 vaccines: The ICP in the case of SARS-COV-2 has not been completely laid out. Since the COVID-19 vaccines have the potential risk of causing symptoms similar to that of enhanced respiratory disease (ERD) parallel studies are to be conducted to collect data and understand the severity of vaccine-induced ERD. Older participants (55 years and above) can be registered for FIH trials unless there are no risks for any other comorbidities. Early clinical studies should also include individuals who are at a high risk of infection i.e. healthcare professionals.