Updated 12/04/2021
Quick read – COVID Vaccines important points
WHAT ARE VACCINES AND HOW DO THEY WORK
A vaccine consists of pathogens, which are micro-germs (microbes- 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 pathogens. The body’s immune system takes some time in the process of recognition, activation, and initiation of such a specific adaptive immune 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 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 they 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 and under development for COVID.
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. Sometimes in killed vaccines, substances called adjuvants (alumunium salts) are 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 like a protein or polysaccharide subunit (containing the antigens), is given to 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. Like killed vaccines, these are also safe in people with weakened immune systems. Examples include the protein subunit vaccines like acellular pertussis (aP), recombinant hepatitis B and human papillomavirus (HPV) vaccines, and polysaccharide subunit ones like pneumococcal (PPSV) and meningococcal (Men-ACWY) vaccines. A protein subunit vaccine for COVID is in the regulatory approval filing stage from Novavax, USA.
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 or toxoid) as a carrier so that the immune system generates a stronger response to the weak antigen. An example is the pneumococcal conjugate vaccine (PCV) which is preferred over the subunit polysaccharide vaccine especially in people with immature immune systems (children) and waning immunity (elderly). Similarly, the meningococcal ACWY vaccine consists of polysaccharide subunits conjugated with the diphtheria toxoid. Others include Hemophilus influenzae (Hib) and typhoid conjugate vaccines.
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.
Combining vaccines
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.
Some vaccines have multiple variations (serotypes) of the virus or its subunits for better protection as seen in the pneumococcal conjugate vaccine (PCV-7, PCV-9, PCV-10, and PCV-13), pneumococcal polysaccharide vaccine (PPV23), and the trivalent and tetravalent flu vaccines (influenza A and B).
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. This is like setting up factories inside our bodies to produce the desired antigen in large amounts to generate effective and more lasting immunity. The immune response consists not only of antibody production (humoral immunity) but also of immune cells causing direct destruction of the viral antigen (T cell or cell-mediated immunity).
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.
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 has also been recently approved.
mRNA vaccines
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 the transcripted genetic information can produce the desired viral antigenic protein in our body. This technology enables the manufacturing of large quantities of vaccines quickly.
Examples are 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.
HERD 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.
SIDE EFFECTS AND COMPLICATIONS OF VACCINATION
Any medicine, treatment, or vaccine can have side effects. All vaccines are thoroughly tested for safety in clinical trials before they enter the market for general population use.
Common
In the majority of cases, vaccines produce none or minimal side effects like transient pain or swelling at the injection site, fatigue, weakness, headache, muscle/joint pains, chills, or fever. These symptoms seldom last more than a day or two, and usually do not need any treatment, though sometimes one or two doses of medicines for pain or fever may be prescribed.
Rare
An allergic reaction that can sometimes be serious (called anaphylaxis) can occur rarely. Though this is seen mainly in people who have a history of allergic reactions, it can also occur unexpectedly. It has in some cases been linked to the presence of substances like polyethylene glycol (PEG) or polysorbates in vaccines. 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. These reactions can be managed with adrenaline (epinephrine) injection in severe cases, and with antihistamine medicines in milder allergic reactions. Often people with a history of allergies carry such medicines with them, and these are available at vaccination centers.
Neurological side effects have also been very rarely reported with vaccines, which can be seen even a few days or weeks after taking the vaccine. These include Bell’s palsy, Guillain-Barre syndrome, transverse myelitis, multiple sclerosis, meningitis, encephalitis, and seizures. Though worrisome as it may sound, these are extremely uncommon, and most of these cases recover well.
COVID VACCINES
Currently available COVID Vaccines
The mRNA vaccine from Pfizer-BioNtech has been approved for public use in the UK, EU, USA, Canada, Israel, UAE, and Singapore, while the Moderna mRNA vaccine has been approved in the USA, UK, EU and Canada.
The Oxford-Astra Zeneca adenoviral vector vaccine has received approval in the UK, EU, Argentina, Mexico and in India (called Covishield in collaboration with Serum Institute, Pune), while Sputnik V adenoviral vector vaccine has been approved in Russia (developed in India with Dr. Reddy’s Labs) and in UAE. Single dose adenoviral vaccine from Johnson and Johnson has recently been approved in USA and EU.
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.
These vaccines are to be given as 2 doses with the optimal immunity against COVID setting in around 2 weeks after the second dose. The dosage interval is around 4 weeks for these vaccines, however, for the Astra Zeneca vaccine it can be up to 12 weeks.
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. As of March 2021, around 420 million people (starting with healthcare and frontline workers, elderly and those at risk with comorbidities) the world over have been vaccinated with various COVID vaccines. As part of GAVI (Global Alliance for Vaccines and Immunisation, WHO), the COVID-19 Vaccines Global Access (COVAX) is acting as a platform to support the research, development, and manufacturing of a wide range of COVID-19 vaccines to ensure that participating countries, regardless of income levels, will have equal access to these vaccines once they are developed. The initial aim is to have 2 billion doses available by the end of 2021, to protect all high risk and vulnerable people, and frontline healthcare workers.
COVID Vaccines: Concerns and Facts
a) These are new vaccines: It is natural for the public to have apprehensions about COVID vaccines due to their new technology and fast-track development. However, these new technologies have been in development for a long time. While mRNA vaccines are being used for the first time in humans during COVID, they have been used successfully in veterinary practice and also evaluated in humans in the past for Zika virus. The adenoviral vector vaccine technology has already been evaluated in humans against the Ebola virus and malaria.
b) Have they been tested enough: Vaccines for COVID have undergone rigorous phase 2 and phase 3 clinical studies in thousands of people, which have confirmed the production of neutralizing antibodies and the prevention of suffering from COVID. The results of many of these studies are also available in the public domain, while some are still being peer-reviewed. The participants of these clinical trials will continue to be monitored for evaluation of long-term immune protection and safety.
c) How long will the immunity last: As of now, the immunity is expected to last 6 months to even a year, however, the real-world effectiveness and safety, along with the duration of protective immunity in the population will be continuously and closely monitored. Thereafter, based on data, recommendations for annual booster shots will be released.
d) What about the new COVID strains: As of now, there is no evidence to suggest that the vaccines will not work against variant strains, though the absolute level of immunity developed may vary. In case of drastic mutations occurring in the future in the COVID-19 virus, the vaccines may be suitably updated.
e) Are they safe and what are the expected adverse effects: Like with all available vaccines, a few of the mentioned side effects have been seen in clinical trials with these COVID vaccines as well, however, these have been mild and shown recovery. Overall high level of safety in all phases of the trials has been seen and documented for these new vaccines.
f) Who should take which vaccine: In an ongoing pandemic, it is best for all adults to take whichever vaccine is available 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. Health care workers, frontline workers, and the elderly especially those with comorbidities should be prioritized in the immunization drive. Even those who have had COVID should take the vaccine, but only after complete recovery. People who are immunocompromised or on immune suppressant medication may not produce an optimum immune response as others but should still take the vaccine, as some protection is better than none, especially to prevent complications and mortality.
The benefits of taking vaccines and being protected, far outweigh the risk and damage of suffering from COVID.
Many of these vaccines have now received emergency use authorization (EUA) by the regulatory authorities of various countries after thorough scrutinization and review of trial efficacy and safety data. Vaccination against COVID has begun in full swing in several countries. Public vaccination has been initiated with health care workers and front-line workers, high-risk groups like the elderly and those with comorbidities, and then will be given to the general population.
Other vaccines if recommended, other than COVID should be given with a gap of 2 weeks (preferably 4 weeks for live vaccines) before/after the COVID vaccine dose.
In the case of COVID vaccines, a question in people’s minds is that can masks, and social distancing be given up once a person is vaccinated. The answer lies in the fact that even post-vaccination, one can be an asymptomatic carrier so you may not suffer COVID but can give it to someone who is previously unexposed or does not have protection by either natural immunity or vaccine. Therefore to reach the stage of pre-COVID normalcy, more and more people will have to take the vaccine to achieve effective herd immunity.
Important points for COVID vaccines
The period of 10 days to 2 weeks after taking the vaccine, is usually a window period where the immune response of the body and antibody production is occurring. Therefore, at this time, the person may still be susceptible to the infection, as the immune protection is yet to reach its optimum. It is also important to take all the recommended doses for effective immunization.
Other vaccines if recommended, other than COVID should be given with a gap of 2 weeks (preferably 4 weeks for live vaccines) before/after the COVID vaccine dose.
In the case of COVID vaccines, a question in people’s minds is that can wearing masks in public, and social distancing be given up once a person is vaccinated. The answer lies in the fact that even post-vaccination, one can be an asymptomatic carrier so one may not suffer COVID but can give it to someone who is previously unexposed or does not have protection by either natural immunity or vaccine. Therefore to reach the stage of pre-COVID normalcy, more and more people will have to take the vaccine to achieve effective herd immunity.
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.
References
Vaccination recommendations by age
COVID Vaccine trials:
Astra Zeneca- Oxford Adenoviral vector vaccine
Astra Zeneca-Oxford vaccine pooled analysis
COVISHIELD and COVAXIN – India
India COVID Vaccination- real-world survey and evidence
Sputnik V human Adenoviral vector vaccine
Johnson and Johnson Adenoviral vector vaccine
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1 Comment
Thank you for pointing out that vaccines can help protect people from dangerous diseases. My son is headed back to school next week, so I’m thinking about taking him to a pediatrician to get vaccinated as soon as I can. I’m going to search for a reputable pediatric clinic in my area that does child vaccinations.