GN Bhat & Dr Nawab John Dar

Vaccines train the body’s immune system to fight a disease that it has not encountered before. The first vaccine was developed by Edward Jenner (1796), when used the cowpox virus (Vaccinia) to inoculate against smallpox in humans. Vaccination is one of the great achievements of medical science. It has provided protection against diseases like measles, polio, tetanus, diphtheria, tetanus meningitis, influenza, and typhoid. Vaccines are often confused with anti-serum, where antibodies taken from another organism are injected into the blood stream, offering temporary protection in a passive manner. In contrast, vaccines provide active immunity. They prepare the body in a memory-induced way as the immune system remembers the imitating infectious agent and remains ready to deal with it if it somehow enters the body in the future.

Clinical Trials
Vaccine development takes place in two phases, preclinical and clinical. Preclinical studies are conducted in two different paradigms, what we call as in-vitro and in-vivo. These preclinical studies conducted in laboratory using appropriate animal model (in-vivo) or human cells (in-vitro) are directed towards establishing the physical, chemical and biological characteristics of the candidate vaccine. These studies may also provide clues about the possible risks of the vaccine and its evaluation in terms of efficacy and safety. Here we need to keep in mind that the results established from these models do not necessary translate when tested in humans. That’s the main reason why most of the drugs/ vaccines fail in clinical trials.
Next step is clinical research and development of the vaccine which includes three phases. Phase I includes initial testing of the vaccine on a small number of individuals of about 20-30 healthy adults. Phase I studies are primarily concerned with safety and tolerability. Phase II studies are used to obtain preliminary information about the vaccine’s ability to produce the immune response, called as immunogenicity, in the target population and general safety of the vaccine candidate. The vaccine is tested on that group of population whose age and health is similar to the people for whom the vaccine is intended. Phase III is the most important, as sufficient data has to be obtained to demonstrate that the new product is safe and effective.
The testing of the vaccine may be done on non-human primates like monkeys but this is possible only if an appropriate disease model is available. The immune response data obtained from the animal model can help to select the doses, schedules, and routes of administration, which are to be evaluated in clinical trials.

Vaccine for Covid-19
Multiple strategies for vaccine development across the globe are being used to combat Covid-19. Some have shown very promising results in pre-clinical studies. Based on these pre-clinical results, several companies along with National Institute of Health (NIH), USA, have started Phase I clinical trials. The first clinical trial started by USA is an open-label, dose-ranging trial in males and non-pregnant females, 18 to 55 years of age. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by Moderna TX, Inc. mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated vaccine that encodes for a full-length, pre-fusion stabilized spike (S) protein of SARS-CoV-2. This study started on March 3 and the expected end date is June 1, during which 45 participants will be tested. Another study is going on at University of Oxford, which is based on a chimpanzee adenovirus vaccine vector called ChAdOx1. This study is recruiting up to 510 healthy adult volunteers aged 18-55 years.
Similarly, China is doing a Phase 1 clinical trial, which is based on a recombinant novel coronavirus vaccine that incorporates the adenovirus type 5 vector (Ad5). There are 108 participants between 18 and 60 years who will receive low, medium, and high doses of Ad5-nCoV. The study is due to complete in December 2021. There are several other similar studies based on different biological approaches which are being approved and are actively recruiting participants for the trials. However, we need to understand and remind ourselves that there is currently no vaccine in the market and even if the one is developed it will reach us at least after a year.
The basic principles for the production and control of vaccines and up-to-date methods for standardisation of assays for vaccine development are described in Technical Report Series (TRS) of World Health Organisation (WHO).

The writers started their scientific career together and now write for general public interest.

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