|Year : 2021 | Volume
| Issue : 4 | Page : 200-205
COVID-19 Vaccines: A weapon for global security
Vasantha Kamath, B Nivea
Department of Medicine, MVJMC and RH, Bengaluru, Karnataka, India
|Date of Submission||15-Jun-2021|
|Date of Decision||28-Jun-2021|
|Date of Acceptance||29-Jun-2021|
|Date of Web Publication||20-Oct-2021|
Dr. Vasantha Kamath
Department of Medicine, MVJMC and RH, Hoskote, Bengaluru - 562 114, Karnataka
Source of Support: None, Conflict of Interest: None
Infectious agents are still in circulation in different parts of the world, and globalization, with travel on the agenda, migration, and poverty, makes vaccination a tool more than ever necessary. Despite the impressive number of studies carried out since the virus was first characterized, there are still many unknowns about this disease. Moreover, it is precisely these unknowns that fully justify the very different conceptual and technological strategies that are currently pursued in the preparation of vaccines against COVID-19. Due to the short development time and the novelty of the technologies adopted, these vaccines will be deployed with several unresolved issues that only the passage of time will permit to clarify. Technical problems connected with the production of billions of doses and ethical ones connected will be needed to ensure equitable global access, protection of diverse subjects, and immunity against viral variants.
Keywords: COVID-19, COVAXIN, COVISHIELD, vaccine
|How to cite this article:|
Kamath V, Nivea B. COVID-19 Vaccines: A weapon for global security. APIK J Int Med 2021;9:200-5
| Introduction|| |
SARS-CoV-2 is not the first virus to sweep across the globe, triggering a pandemic. Ever since the 1918 influenza pandemic and the discovery that a virus was its cause, scientists have been developing ways to monitor the emergence of new pathogens, as well as strategies to stay a step ahead of them through the development of vaccines, drugs, and diagnostics. India is currently in the grip of the second wave of the COVID-19 pandemic. Apart from the previously known strains, a new double-mutant strain B.1.617.2 (Delta) of the SARS-CoV-2 virus has been detected in India, in addition to UK (Alpha), South African (Beta), Brazilian (Gamma), and Californian (Epsilon) variants of the virus already circulating in our country. Vaccinations are one of the most impactful public health measures in existence against infections. The development of a vaccine against SARS-CoV-2 has been viewed as a tool to control the COVID-19 pandemic and as a path toward recovery for our society., The development of several COVID vaccines in less than a year has given us all hope of a release from the pandemic. Now, the goal has shifted to ensuring widespread vaccine coverage across the globe.
| Timeline of Vaccine Development|| |
Vaccines are one of the monumental achievements in human medical intervention to mitigate the dispersion and impact of infectious disease. Vaccine development is an arduous process, taking about 10–15 years on average to accomplish, because one must study the safety, efficacy, dosing levels, risk rate, failure rate, and adverse effects. However, because of the urgency of producing vaccine, it led to a compressed time schedule for COVID vaccine, [Figure 1].
- From the time of the first polio outbreak in the United States to testing and development of vaccine was almost 60 years
- More recently, a vaccine for the lethal hemorrhagic fever elicited by Ebola disease took on a substantially different timeline of at least 15 years for authorized clinical use of an Ebola vaccine
- SARS was reported in February 2003 in Asia and spread to 26 countries and MERS was reported in Saudi Arabia in 2012 and spread to 27 countries and still there are no approved vaccines for both
- After coronavirus was isolated in December 2019, and its genetic sequence was published on January 11, 2020, there was an urgent international call for the development of a COVID-19 vaccine
- The Pfizer–BioNTech partnership submitted to the FDA for the mRNA vaccine BNT162b2 on November 20, 2020. On December 2, 2020, the United Kingdom became the first country in the Western world to approve the use of any COVID-19 vaccine. As of December 21, many countries and the European Union have approved the Pfizer–BioNTech COVID-19 vaccine. A week later, they granted approval for the Moderna vaccine.
| Types of COVID-19 Vaccines|| |
There are four main types of COVID-19 vaccines: 
- WHOLE VIRUS: There are two types of whole virus vaccines – live attenuated and the inactivated vaccines. Examples: Indian COVAXIN, Beijing Institute of Biological Products COVID-19 vaccine, and Wuhan Institute of Biological Products COVID-19 vaccine are all inactivated vaccines
- PROTEIN SUBUNIT: Rather than injecting a whole pathogen to trigger an immune response, subunit vaccines sometimes called acellular vaccines contain purified pieces of it, which have been specially selected for their ability to stimulate immune cells. Examples: Novavax
- VIRAL VECTOR: Here, COVID-19 spike proteins found on the surface of the virus are injected into human cells by a modified virus (vector) to deliver genetic code for antigen, thereby triggering an immune response. Examples: Sputnik, COVISHIELD, and Johnson and Johnson vaccine
- NUCLEIC ACID (RNA and DNA): These vaccines insert genetic material from a disease-causing pathogen into host cells to stimulate an immune response against it. Examples: Pfizer–BioNTech and Moderna-RNA vaccine.
| BNT162 mRNA (Pfizer-BioNTech)|| |
It is a mRNA vaccine. In December 2020, UK became the first country in the world to approve this vaccine. BioNTech, working together with Pfizer, started testing its BNT162 vaccine in humans in global trials. Its data showed a vaccine efficacy rate of 95%, and even in adults over 65 years, efficacy was more than 94%, which is reassuring as older people do not always have a strong immune response to vaccines. It is a 2-dose series given 21 days apart.
| mRNA 1273 (MODERNA)|| |
It is a mRNA vaccine, developed by Moderna, in Cambridge, Massachusetts. As with the Pfizer vaccine, this RNA vaccine will need to be kept in ultra-cold freezers. The final trial results confirm this vaccine has a 94% efficacy rate. It is administered as a 2-dose series given 28 days apart.
Two vaccines COVISHIELD and COVAXIN have been granted emergency use authorization (EUA) by the Central Drugs Standard Control Organisation in India [Table 1].
| Covaxin|| |
COVAXIN, India's indigenous COVID-19 vaccine by Bharat Biotech, is developed in collaboration with the Indian Council of Medical Research–National Institute of Virology (NIV). The indigenous, whole-virion inactivated vaccine is developed and manufactured in Bharat Biotech's Bio-Safety Level 3 high containment facility., It is a vaccine with no reconstitution requirement and ready to use liquid presentation in multidose vials, stable at 2°C-8°C. COVAXIN demonstrated efficacy of 70%–80%. Analysis from the NIV indicates that COVAXIN-induced antibodies can neutralize the UK variant and other heterologous strains. It is a 2-dose vaccination regimen given 28 days apart.
| COVISHIELD/ASTRAZENECA|| |
This is a viral vector vaccine, developed at the University of Oxford in collaboration with AstraZeneca, named ChAdOx1 nCoV-19, is based on a chimpanzee adenovirus. Its efficacy rate is 70%–90% and has been granted EUA by the European Medicines Agency. In India, it is manufactured by Serum Institute of India. This vaccine is fridge-stable, meaning that it can be easily transported anywhere in the world. It is a 2-dose series given 4–12 weeks apart.
| New COVID-19 Vaccine Approved in India|| |
A third coronavirus vaccine has been approved for use in India amid the deadly second wave. SPUTNIK V's approval came as India overtook Brazil to become the country with the second-highest number of cases globally. The Russian Direct Investment Fund, which is marketing the vaccine, has signed deals to produce more than 750 million doses of Sputnik V in India with six domestic vaccine makers. Hyderabad-based pharmaceutical Dr. Reddy's Laboratories will be importing the first batch of 125 million doses to India during this quarter.
| Sputnik v|| |
In Russia, the Gamaleya Research Institute developed a vaccine named Sputnik V, a combination of Ad5 and Ad26, each engineered with a coronavirus gene. The purpose of using two different adenoviruses is to increase the effectiveness of the vaccine., It is administered as a 2-dose series, given 3 weeks apart.
| DNA Vaccines|| |
DNA vaccines are based on plasmid DNA that can be produced at large scale in bacteria. Typically, these plasmids contain mammalian expression promoters and the gene that encodes the spike protein, which is expressed in the vaccinated individual upon delivery. The great advantage of these technologies is the possibility of large-scale production in Escherichia coli, as well as the high stability of plasmid DNA. However, DNA vaccines often show low immunogenicity and have to be administered via delivery devices to make them efficient. This requirement for delivery devices, such as electroporators, limits their use. Four different DNA vaccine candidates against SARS-CoV-2 are currently in phase I/II clinical trials. INDIA'S ZyCov-D, the DNA vaccine against COVID-19 developed by Gujarat-based company Zydus Cadila, could be on its way to becoming the first approved DNA COVID vaccine in the world.
| Salient Features about COVID Vaccines|| |
India's huge immunization drive began on January 16, 2021.
- The 1st group to receive included the health care and frontline workers
- The 2nd group of persons to receive, were 60 years and above, and persons between 45 and 59 years with comorbidities from March 1, 2021
- The 3rd group from April 1, 2021, were people above 45 years
- The 4th group from May 1, 2021, were people above age of 18 years.
All approved vaccines prevent death and serious infections. There is no difference in the efficacy data when choosing vaccine.
There is no requirement for screening of the vaccine recipients by Rapid Antigen Test before COVID-19 vaccination. Vaccination to be encouraged in elderly population as risk of mortality is high.
COVID vaccines will not cause a positive test result for a COVID-19 PCR or antigen test. This is because the tests check for active disease and not whether an individual is immune or not. However, it may be possible to test positive in an antibody test that measures COVID-19 immunity in an individual.
Nasal vaccines may be able to prevent asymptomatic COVID, because it generates local IgA antibodies cutting chains of transmission, bringing an end to pandemic.
History of immediate allergic reaction of any severity to COVID/non-COVID vaccines or any component of vaccine like polyethylene glycol/polysorbate of mRNA vaccine– to avoid vaccination. But people with allergy to food, drugs, latex-can safely take vaccination.
People with nasal allergy, skin allergy, and bronchial asthma can be vaccinated.
In people who had COVID-19 in the past or who have received plasma therapy or anti-SARS-2 monoclonal antibodies, vaccination is deferred by 3 months.
In individuals who have received the first dose and got COVID-19 infection before completion of the dosing schedule, the 2nd dose should be deferred by 3 months from clinical recovery of COVID-19 illness.
An individual can donate blood after 14 days of either receipt of COVID-19 vaccine or testing RT-PCR negative if suffering from COVID-19 disease.
People with diabetes, chronic kidney disease, liver disease, malignancy, and other comorbidities can be vaccinated safely.
People on immunosuppressants can be vaccinated and vaccine is unlikely to increase autoimmunity; hence, patients with autoimmune disease can be vaccinated.
People on steroids– decrease dose of oral steroid 7.5 mg/day for 6 weeks. Higher dose act as immunosuppressive and reduce immunity, inhaled steroids need not be tapered as systemic bioavailability of inhaled steroid is low.
Patients on antiplatelet agents such as aspirin and clopidogrel can safely take vaccination.
Patients on anticoagulation– If INR is <3 vaccinate, if it is more than 3-dose adjustment of anticoagulants is done to bring INR <3 and then vaccinate.
Patients who planned to undergo surgery take vaccine 2 weeks in advance for protection.
There is no prohibition of alcohol before and after vaccination.
Menstruation is not a contraindication for vaccination in girls more than 18 years of age.
| Post-COVID Immunity Status|| |
Immunity following natural COVID infection, based on experience with previous SARS-COV 1 and MERS infections, has shown that protective IgG antibodies rise after COVID infections. After 3–4 months, their levels go down to certain level, but are usually detectable up to 2 years. The antibody level at which there is protection against COVID-19 infection remains unknown. Hence, we expect vaccine immunity to follow similar rules, as set by natural infection with COVID-19. Estimates say that at least 70% of our population need to get immunity either by natural infection or by vaccination. Until this figure of 70% immunity is crossed, infection is unlikely to stop.
| Vaccine-Related Adverse Events|| |
Adverse reactions to vaccines are commonly reported, but most are not immunologically mediated. Commonly reported side effects of COVID-19 vaccines include pain at the injection site, fever, headache, myalgia, irritability, etc.
| Astrazeneca/Johnson and Johnson: Causal Link to Severe Thrombosis Established|| |
Cases of thrombosis with thrombocytopenia with the Ad26.COV2. S (Janssen [Johnson and Johnson]) and AZD-1222 (AstraZeneca) vaccines have been reported. The FDA temporarily paused use of Ad26.COV2. S in the mid-April 2021 to evaluate rare cases of cerebral venous sinus thrombosis. After discussing the benefits and risks of resuming vaccination, the Advisory Committee on Immunization Practices reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged 18 years and older with a warning that rare clotting events may occur after vaccination, primarily among women aged 18–49 years. Two scientific studies published in April 2021 established a causal relationship between the AstraZeneca COVID-19 vaccine and severe thrombotic complications and reached the same conclusion that these unusual severe thrombotic events are accompanied by thrombocytopenia that are caused by rogue antibodies directed against platelet factor 4 (PF4). Patients can, therefore, have both severe thrombosis and severe bleeding. The syndrome is very similar heparin-induced thrombocytopenia and is diagnosed and treated in the same way, with the administration of intravenous immunoglobulins and anticoagulants. The syndrome associated with the vaccine has been named, vaccine-induced immune thrombotic thrombocytopenia.,
The American Society of Hematology has published the documents for clinicians to be aware of symptoms, diagnosis, and treatment if TTS is suspected.
Diagnosis includes the following 4 criteria: ,
- COVID vaccine (Johnson and Johnson/AstraZeneca) 4–30 days previously
- Venous or arterial thrombosis (often cerebral or abdominal)
- Positive PF4 ELISA.
The following symptoms associated with TTS may emerge 4–30 days after vaccination with Ad26.COV2. S or AZD-1222:
- Severe headache
- Visual changes
- Abdominal pain, nausea, and vomiting
- Back pain
- Shortness of breath
- Leg pain or swelling
- Petechiae, easy bruising, or bleeding
| Anaphylaxis to Vaccination|| |
21 and 10 cases of anaphylaxis associated with Pfizer (11.1 cases/million doses administered) and Moderna (2.5 cases/million doses administered) have been reported, respectively. The overall incidence of anaphylaxis to COVID-19 mRNA vaccines is very low.
| COVID-19 Vaccination in Pregnancy and Lactation|| |
Vaccination during pregnancy is warranted as COVID-19 infection during pregnancy increases the risk of preterm birth by 2–3 times. Also, when risk of exposure is high as in case of health-care workers and pregnant women with comorbidities. Vaccination trials conducted in the US on 94,335 pregnant women with Pfizer/Moderna vaccines were followed up to 3 months, with no adverse events. Currently, there have been no trials with COVAXIN and COVISHIELD on pregnant women; however, technically, this should not impose any concerns. Vaccination is recommended for all lactating women.
| Vaccination in Adolescents and Children|| |
In the United States, vaccination was opened to all aged 16 years and older in early April 2021. On May 10, 2021, the FDA extended the EUA for the BNT162b2 vaccine to include younger adolescents aged 12–15 years. The mRNA-1273 vaccine was reported to be 96% effective in an initial analysis of a phase 2/3 trial (n = 3,235) in adolescents aged 12–17 years. Clinical trials for other vaccines are ongoing for adolescents and children.
| Duration between Vaccine Doses|| |
Given that the current supply of vaccines remains limited, some have suggested delaying the second vaccination to provide at least 1 dose to a larger number of people. The CDC has indicated that the second immunization can be administered up to 42 days, or 6 weeks, after the initial inoculation. Concern has been raised that lengthening the time between vaccines will leave individuals with longer periods of time with only partial protection and might contribute to the emergence of additional variants. The CDC has discouraged people from mixing vaccines unless there are “exceptional situations.”
| Effect of Vaccines on Variants|| |
If SARS-CoV-2 continues to spread, mutations will occur, and new variants will emerge. Among the dominant variants currently in circulation, data suggest that the Moderna vaccine effectively neutralizes the B.1.1.7 (Alpha), UK variant (89%), but that there is a decrease of neutralization ability to the B.1.351 (Beta) South Africa variant (60%). Data from Israel suggest that the Pfizer-BioNTech vaccine is effective at the population level in a country where the B.1.1.7 (Alpha) variant is now predominant.
| Breakthrough Infections|| |
Worldwide, 5.5% of the population is fully vaccinated. Recent statement from the Indian Council of Medical Research states that 2–4 per 10,000 got infected with COVID-19 after vaccinations in INDIA. A total of 10,262 SARS-CoV-2 vaccine breakthrough infections had been reported from 46 US states and territories as of April 30, 2021. There are several possible explanations for breakthrough infections. The human immune response is encoded in our DNA and varies from person to person. This variability helps us to respond to an array of germs. However, the effectiveness of these responses is also variable likely due to poor health, medication, or age.
- The immunity against COVID-19 does not build immediately after the first dose or even immediately after the second. Full-fledged immunity takes a few weeks after the second dose
- Immunity is not absolute. Even after complete vaccination, a person can get infected. His/her chance of dying or getting a severe infection requiring hospitalization will be substantially less though
- Not all vaccines work to the same extent. The efficacy varies
- Not all vaccines are effective against all the variants.
| Peltzman Effect and Its Importance|| |
PELTZMAN EFFECT means behavior compensating for the perceived risk. In other terms, people become more careful when they sense greater risk and less careful if they feel more protected. This means that vaccines are giving a sense of security, which leads to an increased risky behavior. However, the problem is that while vaccines neither give immediate protection nor full protection, the sense of security unfortunately starts much earlier, even before the actual injection. The mask usage, social distancing, and hand sanitization have become progressively less. While this is attributed mainly to pandemic fatigue, the Peltzman effect cannot be ignored. It is important to be aware of Peltzman effect and be more careful until the effect of vaccination takes us close to herd immunity.
| Herd Immunity May Be Impossible in India|| |
- Even with vaccination efforts in full force, estimates placing theoretical threshold at 60%–70% for vanquishing COVID-19 looks out of reach-say scientists who are modelling pandemic progress
- Vaccine prevents people from getting sick with COVID, but unclear to what extent they can block the transmission
- Perfectly coordinated global vaccine campaign might have wiped out COVID-19, but the roll out is uneven
- There is no authorized vaccine for children
- New variants might be more transmissible and resistant to vaccine
- Since it is not clear how long the acquired immunity to infection lasts, it is obvious that when the immunity wanes, people become more susceptible to reinfection and do not contribute to herd immunity
- Herd immunity threshold gets higher when people relax vigilance.
| Covax|| |
In an unprecedented show of global solidarity, the world came together to back COVAX, a unique global solution aimed at making equitable access to COVID-19 vaccines possible. People in 122 economies have already received COVAX doses. By the end of the year, the program will have delivered at least 1.3 billion doses, and possibly 1.8 billion by early 2022, to people in 92 lower-income countries who would otherwise have limited or no access to them. India has shipped 64 million doses of vaccines to 86 countries in Latin America, the Caribbean, Asia, and Africa. Both COVISHIELD and COVAXIN have been exported, some in the form of “gifts”, others in line with commercial agreements signed between the vaccine makers and the recipient nations, and the rest under the COVAX scheme, which is led by the WHO.
The other candidates which are in different stages of trials in India to test safety and efficacy include: 
- ZyCov-Di, being developed by Ahmedabad-based Zydus-Cadila
- A vaccine being developed by Hyderabad-based Biological E, the first Indian private vaccine-making company, in collaboration with US-based Dynavax and Baylor College of Medicine
- Hyderabad-based Biological E to produce the vaccine developed by US firm Johnson and Johnson
- HGCO19, India's first mRNA vaccine made by Pune-based Genova in collaboration with Seattle-based HDT Biotech Corporation, using bits of genetic code to cause an immune response
- A nasal vaccine by Bharat Biotech.
| Conclusion|| |
The invention of vaccination was a turning point in the war between microbes and humans and the world has transformed in the past year and some aspects of life may remain changed forever. Moreover, in addition, COVID-19 may reoccur seasonally, like other respiratory viruses, most notably influenza.
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Conflicts of interest
There are no conflicts of interest.
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