WHAT ARE VACCINES AND HOW DO THEY WORK
A vaccine consists of pathogens, which are micro-germs (bacteria or virus) in killed (inactive) or weakened (attenuated) form, or their parts/genetic material, which on entering the human body help in producing immunity against that infection without actually suffering from it.
Our body’s immune system can recognize specific parts of these pathogens called ‘antigens’, and in response produce ‘antibodies’ and activate immune cells with memory, which can destroy these microbes. The body’s immune system takes some time in the process of recognition, activation, and initiation of such a response. In this window period, the invading microbe can rapidly multiply and overwhelm the immune system, thereby producing symptoms and causing damage. However, if vaccinated, the body’s immune system is ready to immediately fight off the actual active organism when exposed, preventing it from causing the disease.
Vaccination is the process of giving a vaccine while immunization refers to the body developing immunity against that particular infection. Inoculation refers to introducing microbes into any medium, and in this case, is synonymous with vaccination.
TYPES OF VACCINES
Vaccines have conventionally used either the whole or a part (containing the antigens) of the disease-causing micro-pathogen for immunization. Now new types of vaccines using genetic technology have been developed during the COVID pandemic and are now becoming available in many countries.
Whole microbe vaccines
Killed (Inactivated) – These vaccines contain the whole organism but killed and inactivated by heat or chemicals so that it cannot cause any disease but can be recognized by the body’s immune system. Examples are injectable vaccines for Influenza (Flu), Pertussis (whooping cough), Hepatitis A, Polio, and Rabies. The COVID vaccines Covaxin (Bharat Biotech-ICMR-NIV India) and the vaccines from Sinovac/Sinopharm, China are killed vaccines.
Live weakened – Also called live attenuated, these vaccines contain the virus in a highly weakened form therefore incapable of causing disease, (or sometimes causing extremely mild symptoms). Examples are the injectable vaccines for Tuberculosis (BCG), Measles, Mumps, Rubella (MMR), Chickenpox (Varicella), and Rotavirus, along with the oral (mouth drops) vaccine for Polio, oral capsule vaccine for Typhoid, and the nasal spray vaccine for Flu.
Killed-inactivated versus live-weakened Vaccines
The advantage of giving a live vaccine is that since the organism can multiply in the body, the immune response and antibody production is much greater and long-lasting, as compared to killed vaccines, and therefore additional booster doses may not usually be needed. In killed vaccines, substances called adjuvants may be added to further enhance the immune response.
Live vaccines are to be avoided in people with compromised or suppressed immunity, in whom killed vaccines can be safely given. Live vaccines also require more stringent storage and cold chain. Extremely rare cases of live weakened pathogens mutating to a stronger infective (virulent) form have been reported.
Part microbe vaccines
Subunit vaccines – Instead of the whole organism, a part of it (containing the antigens) like a surface protein or polysaccharide, is given which can produce a stronger immune response. These subunits can be isolated from the organism by chemical disintegration, or prepared in the laboratory by genetic recombinant technology. Examples include acellular Pertussis (aP), Hemophilus influenzae (Hib), and Hepatitis B (recombinant) vaccines. Like killed vaccines, these are also safe in people with weakened immune systems.
Conjugate vaccines – It is a type of subunit vaccine where a weak antigen (like a polysaccharide), is combined with a strong antigen (like a protein) as a carrier so that the immune system generates a stronger response to the weak antigen. Example are the Pneumococcal conjugate vaccine (PCV13) and Typhoid.
Toxoid vaccines – These consist of inactivated toxins (toxoids) released by certain bacteria that cause the disease, and are recognized by our immune system. Examples are vaccines for Diphtheria and Tetanus.
Combination vaccines of toxoids and killed vaccines (DPT and DaPT) or multiple live vaccines (MMRV- Measles, Mumps, Rubella, Varicella) are available for more efficient immunization, especially in children.
Routes of Vaccination
Most vaccines are given as injections however, some may be given orally (live typhoid and polio vaccines) or nasally (live flu vaccine). These routes give the advantage of stimulating effective local immunity in the gut or respiratory tract, which are the entry routes of the pathogens.
In some cases, for the same infection, different types and routes of vaccines may be available like for Typhoid (subunit/conjugate injectable and live oral), Polio (killed injectable and live oral), and Flu (killed injectable and live nasal).
New Types of Vaccines
Using the genetic material of viruses to produce the required antigen inside the human body has heralded the new age in vaccine technology and facilitated timely development of vaccines for COVID. This is like setting up factories inside our bodies to produce the desired antigen in large amounts to generate effective and more lasting immunity.
Herd immunity is a form of indirect protection from a particular infection when a sufficient percentage of a population has become immune to an infection, either through vaccination or exposure to the infection itself, thereby reducing the likelihood of infection for individuals who have not been immunized or exposed to the infection. This can happen after more than 50-60% population is exposed to the infection or immunized against it.
Vaccines for COVID are making use of these new technologies which enable a much faster and more large-scale production, which has made availability for clinical trials and public immunization possible during the pandemic. These vaccines do not contain any live virus so cannot cause the disease and are also safe in people even with possible immune suppressive conditions.
These vaccines are to be given usually as 2 doses around 4 weeks apart with the optimal immunity against COVID setting in around 2 weeks after the second dose.
Adenoviral vector vaccines
The genes of the virus for the required antigen (surface spike protein in case of Coronavirus), are loaded into another inactivated virus (vector) like the Adenovirus, and then introduced into the human body. The body will produce antibodies and immune response against the specific antigen as well as the vector. Therefore, if the vector is a virus that humans are routinely exposed to, then there might be pre-existing antibodies against it which can destroy the vector before the viral genes can produce good amounts of required antigens. This can be prevented by using vectors that have low exposure in humans or mainly infect animals.
Examples of such vaccines are the Oxford-Astra Zeneca COVID vaccine using an adenoviral cold virus of chimpanzees, and the Sputnik V vaccine by Gamaleya, Russia which uses two human adenoviral strains (Ad5 and 26). A vaccine from Johnson and Johnson using the Ad26 vector is also being developed.
Genetic information is transferred (transcripted) from the main viral DNA or RNA to a messenger RNA (mRNA) which actually produces proteins by a process called translation. Injecting the mRNA containing this genetic information can produce the desired viral antigenic protein in our body. This has been used as the vaccine technology in the COVID vaccines by Moderna and Pfizer-BioNtech.
Plasmid DNA vaccine
The genes containing information to make the required viral antigen are inserted into the DNA of molecules called plasmids, found in bacteria. These plasmids are then introduced into the human body. A COVID vaccine from Zydus-Cadila called ZyCoV-D is being developed with this technology in India.
Currently available COVID Vaccines
In December 2020, the mRNA vaccine from Pfizer-BioNtech has been approved for public use in the UK, EU, USA, Canada, Israel, and Singapore, while the Moderna mRNA vaccine has been approved in the USA and Canada.
Thereafter the Oxford-Astra Zeneca adenoviral vector vaccine received approval in the UK, Argentina and in India (called Covishield in collaboration with Serum Institute, Pune), while Sputnik V adenoviral vector vaccine has been approved in Russia (being developed in India with Dr. Reddy’s Labs).
Among the killed-inactivated vaccines, India has given emergency conditional authorization to its indigenous COVID vaccine Covaxin (a collaboration of Bharat Biotech, a well-known Indian vaccine manufacturer with the National Institute of Virology and the Indian Council for Medical Research). The Sinovac vaccine Coronavac was approved in China earlier, while the vaccine from Sinopharm has been approved in China, Egypt, Bahrain, and UAE.
The mRNA vaccines need stringent deep-freeze storage temperatures while adenoviral vector and killed-inactivated vaccines can be stored at regular refrigerator temperatures of 2-8 deg C.
Many countries have formed collaborations of their local manufacturing companies with international innovators.
All the vaccines which have got emergency authorization and approval in different countries are safe. They have been tested in thousands of people and the data carefully scrutinized by regulators.
Any vaccine (including the vaccines for other infections being taken over several years) can cause reactions in some people like local injection site pain, stiffness, swelling or irritation, and some general symptoms like fever, body ache, headache and weakness. However, these are mild, and resolve in a day or two.
Severe allergic reactions are very rare (1-10/million), and mostly in people with a prior history. The symptoms can range from mild localized itching, redness and swelling, to itching all over the body with hives, swelling of the lips, sweating, palpitation, and breathlessness. They are manageable with anti-allergic medications (like antihistamines, steroids and epinephrine) available at vaccination centers. Vaccine related neurological effects are also extremely rare and also show resolution.
This far outweighs the risk of suffering from COVID which can lead to complications, hospitalization, long-term health concerns and even death.
HOW DO WE KNOW THE COVID VACCINES WORK?
All the vaccines which have got emergency authorization and approval in different countries, have done so only after testing that the vaccine works by generating adequate protective immunity in the form of antibodies and other cytokine immune markers against COVID in phase 2 studies in hundreds of people.
Vaccine effectiveness shown by vaccinated people not getting COVID, needs a long duration of monitoring and surveillance in a large population. Even so phase 3 studies showing this in thousands of people are either on or completed. It is evident that the vaccines that showed an adequate immune response in phase 2 have also shown efficacy in phase 3 with immunogenicity being a surrogate marker of effectiveness. Therefore, some vaccines have been given emergency authorization based on their immunogenicity and safety data, so that they can be beneficial during the pandemic to meet mass vaccination needs. However, in all such cases, phase 3 is ongoing and its data is being constantly monitored.
As of now, there is no evidence to suggest that the vaccines will not work against variant strains. In case of drastic mutations occurring in the future in the COVID-19 virus, the vaccines may be suitably updated. While genetic vaccines can be updated fast, whole virus inactivated vaccines contain multiple antigens.
Some vaccines with stringent storage conditions may not be feasible in certain countries which may have to opt for vaccines easily storable in a regular refrigerator at 2-8 deg C. Also it is difficult to vaccinate the entire population of some countries with imported vaccines alone, therefore indigenous or collaborative vaccine development and manufacturing holds the key to cater to large scale successful vaccination drives.
CAN ONE GET COVID AFTER BEING VACCINATED?
The vaccines require 2 doses, a month apart and the optimal protective immunity is seen to set in around 2 weeks after the 2nd dose. Therefore, till then you are at risk of getting COVID like any other non-vaccinated person, so the precautions of wearing masks in public, social distancing and frequent hand sanitizing/washing should be followed.
The immunity has seen to last for 6 months and possibly up to a year, however, this is still being monitored and evaluated by regular follow-up of clinical trial participants. Thereafter there will be guidelines released on the timing of repeat/booster vaccination.
No vaccine can give 100% protection, but even if one does get symptomatic COVID, it would be mild with the risk of complications, hospitalization and mortality being avoided.
IS IT COMPULSORY TO GET VACCINATED?
Vaccination against COVID is entirely voluntary.
However, it is highly recommended to get vaccinated for personal protection against suffering from COVID and its sequelae.
Health care workers and front-line workers should all definitely be vaccinated. Elderly people, and those with co-morbidities like diabetes, hypertension, heart/kidney/liver ailments and respiratory conditions, should take the vaccine as they are more prone to developing severe COVID and its complications if infected.
It is also important to get vaccinated for increasing herd immunity in the community as more and more people getting vaccinated can reduce the virus spreading in the unvaccinated population also. There are still some people who cannot be vaccinated like children and pregnant women due to the lack of studies conducted in them.
Vaccination is only possible at designated COVID vaccination centers by prior registration.
Vaccination against COVID has begun in full swing in several countries. As regards, which COVID vaccine to choose, in an ongoing pandemic, it’s best to take whichever vaccine is available to you the soonest as these vaccines do not differ significantly in effectiveness or safety. All these vaccines confer protection against getting ill with COVID and its risk of complications and mortality. Even those who have had COVID should take the vaccine. The benefits of taking vaccines and being protected, far outweigh the risk and damage of suffering from COVID.
Vaccination can prevent suffering from the infection, especially severe infection requiring hospitalization or causing complications, but may or may not prevent asymptomatic transmission. Also, in some people even with proper vaccination, an adequate immune response may not be generated, and the same can vary from person to person. That is why more and more people in the community should be vaccinated so that herd immunity can ensure overall optimum infection control in that population, and also protect the vulnerable individuals.
The benefits of vaccination to individuals and the community far outweigh the risks and side effects. Vaccination has been successful in curbing and preventing several infectious diseases globally and is a scientifically validated, proven, and recommended process.
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