Vaccine: An overview
Edward Jenner in 1796 noted that a crude isolate of cow pox virus prevented infection with potentially fatal and disfiguring pathogenic microorganism, smallpox. With this discovery the field of Vaccinology was born and takes its name from "Vacca", the Latin for cow. Vaccines are proteins, polysaccharides,or pathogenic nucleic acids,that are used to stimulate immunity, to eliminate or weaken pathogens or pathogenic products. In other words, vaccines are biological preparations that help to acquire immunity against dis-eases. Vaccines are usually a virus or bacterium-based preparations, that fight against diseases, caused by viruses or bacteria.
Several aspects are considered by scientists while designing a vaccine. How our immune system responds to the germ? Who needs to be vaccinated against the germ? What is the best technology or approach to be followed for manufacturing the vaccine?Based on a number of these factors, scientists decide which type of vaccine they will make. There are 4 main types of vaccines: (a) Live-attenuated vaccines, (b) inactivated vaccines, (c) subunit, recombinant, polysaccharide, and conjugate vaccines and (d) toxoid vaccines. In addition, scientists are still trying to invent new types of vaccine e.g. DNA vaccine and Recombinant vector vaccines (platform-based vaccines).
Live vaccines use a weakened (or attenuated) form of the germ that causes a disease.Live vaccines are used to protect against Small pox, Chicken pox, Rota virus. Inactivated vaccines use the killed version of the germ that causes a disease. Inactivated vaccines usually don't provide immunity (protection) that's as strong as live vaccines. Inactivated vaccines are used to protect against Hepatitis A, polio etc. Subunit, recombinant, polysaccharide, and conjugate vaccines use specific pieces of the germ - like its protein, sugar, or capsid (a casing around the germ).
These vaccines are used to protect against Hib (Haemophilus influenzae type b) disease, Hepatitis B, HPV (Human papillomavirus) etc. Toxoid vaccines use a toxin (harmful product) made by the germ that causes a disease. They create immunity to the parts of the germ that cause a disease instead of the germ itself. That means the immune response is targeted to the toxin instead of the whole germ. Toxoid vaccines are used to protect against: Diphtheria,Tetanus etc.
Because these vaccines are so similar to the natural infection that they help prevent, they create a strong and long-lasting immune response.
A novel vaccine candidate undergoes an elaborate development process after discovery. Regulatory agencies worldwide divides this development process into preclinical (testing in animals) and clinical (clinical trials in human subjects) stages.
The development of every vaccine starts with the exploratory stage. It consists of laboratory research to identify antigens that might be able to treat or prevent a disease. These antigens could include virus-like particles, weakened viruses or bacteria, weakened bacterial toxins, or other substances derived from pathogens. If the vaccine shows promise in the exploratory phase, it moves on to the animal testing phase.
Prior to regulatory approval, a vaccine candidate usually undergoes three phases of development in humans, which, for the most part, progress sequentially: Phase 1, Phase 2, and Phase 3. After successful completion of Phase 3 trials and following licensure of the product, Phase 4 studies, also referred to as post marketing surveillance studies (PMS) are used to continue to monitor the vaccine for safety and effectiveness in the population.
On the stage of clinical development, the vaccine is tested in humans. The testing happens in four phases and can take many years. First three phases are the clinical trials. The stage of clinical development is based on strict ethical principles. Volunteers are well informed of the vaccine safety and efficacy.
Phase 1 is done in small scale with 20 to 100 healthy volunteers. Its purpose is to determine safety and dosing. In Europe, there are phase 1a and 1b. Phase 1a is for European volunteers and phase 1b for volunteers in developing countries. Vaccines that are targeted to children, are first tested with adults.
Phase 2 is tested with a larger group of 100 to 500 patient volunteers. The purpose of this phase is to evaluate the effectiveness of the vaccine versus clinical diseases and artificial infections. Immune response, alongside side-effects, are also evaluated and the method of the delivery is decided.In this phase the trials are controlled and randomized. A group of people is also having a placebo vaccine in the tests.
Phase 3 confirms the effectiveness and monitors adverse events originating from long term use. This phase is tested with 1000-5000 patient volunteers to evaluate the effectiveness under natural disease conditions. The tests in this phase are randomized and the developed vaccine is tested against a placebo . If the vaccine is safe and effective for a defined period, at that case the manufacturer can apply for a license from the regulatory authorities. If the license is admitted, can the manufacturers start to market the vaccine for human use.
In phase 4, the vaccine has been licensed and is available for the users. The effectiveness of the vaccine is monitored throughout its long-term use. It might include: (1) Does the candidate vaccine prevent disease? (2) Does it prevent infection with the pathogen? (3) Does it lead to production of antibodies or other types of immune responses related to the pathogen?
After a successful Phase 3 trial, the vaccine developer will submit a Biologics License Application to the regulatory authority e.g. FDA. Then the FDA will inspect the factory where the vaccine will be made and approve the labeling of the vaccine.The FDA has the right to conduct its own testing of manufacturers' vaccines. A variety of systems monitor vaccines after they have been approved. They include Phase IV trials, the Vaccine Adverse Event Reporting System (VAERS), and the Vaccine Safety Datalink (VSD). The CDC and FDA established VAERS in 1990.
The goal of VAERS, according to the CDC, is "to detect possible signals of adverse events associated with vaccines. About 30,000 events are reported each year to VAERS. Between 10% and 15% of these reports describe serious medical events that result in hospitalization, life-threatening illness, disability, or death.VAERS is a voluntary reporting system. Anyone, such as a parent, a health care provider, or friend of the patient, who suspects an association between a vaccination and an adverse event may report that event and information about it to VAERS. The CDC then investigates the event and tries to find out whether the adverse event was in fact caused by the vaccination.
The CDC established VSD in 1990. The VSD is a collection of linked databases containing information from large medical groups. The linked databases allow officials to gather data about vaccination among the populations served by the medical groups. Researchers can access the data by proposing studies to the CDC and having them approved.
Vaccines are developed, tested, and regulated in a very similar manner to other drugs. In general, vaccines are even more thoroughly tested than non-vaccine drugs because the number of human subjects in vaccine clinical trials is usually greater. In addition, post-licensure monitoring of vaccines is closely examined. More than 140 vaccine efforts are currently underway in the global push to stop the COVID-19 pandemic, according to the World Health Organization.
The first new vaccine to enter human trials for COVID-19 was developed by the US firm Moderna Therapeutics. About 35 other companies and academic institutions are also working on COVID-19 vaccines. Most are currently in "pre-clinical testing" phase.
Probably the highest-profile effort is the ChAdOx1 nCoV-19 vaccine candidate from Oxford University's Jenner Institute (ChAdOx1 stands for "chimpanzee adenovirus Oxford 1"). The Chinese company CanSino Biologics - the medical science arm of the People's Liberation Army, no less - has completed Phase 1 trials with an adenovirus vector vaccine called Ad5-nCoV. CanSino reported positive results in a Lancet paper on May 22. This is the first Phase COVID vaccine clinical trial anywhere in the world to report full results in a peer-reviewed paper, with 108 healthy adults all showing an immune response to the adenovirus vector vaccine.
The writer is a professor, Department
of Biochemistry and Molecular
Biology, Dhaka University