COVID-19 vaccines - a comparison
Author: Dr. Guneet J Mann, MD
Vaccine is a suspension of weakened, killed, or fragmented virus or bacterium or an isolated subunit of the infectious agent, or a recombinant protein made from the agent or toxins produced by the microorganism, that is administered primarily to prevent disease. Since the introduced agents are foreign to the body, the immune system gets stimulated to generate specific responses against it, thus resulting in development of active immunity against that agent. Once the immune system is stimulated, memory B cells, and in some cases T cells, are generated that remain sensitized and ready to respond to the agent should it gain entry to the body in the form of an actual infection. Some vaccines confer passive immunity by providing antibodies or lymphocytes already made by an animal or human donor. These are used in specific conditions only. What makes vaccines unique is that unlike most medicines that can only treat or cure diseases, vaccines prevent them.
Similar to other vaccines, different types of COVID-19 vaccines stimulate the body to produce “memory” T-lymphocytes as well as B-lymphocytes that will remember how to fight SARS-CoV-2 in the future. After vaccination, a few weeks are required for the body to boot up the immune system and produce these memory cells. During this period a person could be infected with the virus that causes COVID-19 and get sick.
When a sufficient number of individuals in a population are immune to a disease, either as a result of natural infection or vaccination, herd immunity is achieved. This means that if there is random mixing of people within a population, the pathogen will not spread through the population because herd immunity lessens the chances of susceptible or non immune individuals coming in contact with individuals who are infectious. This provides a measure of protection to individuals who are not personally immune to the disease. Historically, herd immunity played an important role in the successful eradication of smallpox.
mRNA (messenger ribonucleic acid) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene. Ribosome is the structure in the cytoplasm of a cell that reads the mRNA and aids in the synthesis of a specific protein molecule, encoded by a specific gene. mRNA vaccines introduce a short-lived, synthetically created fragment of an mRNA sequence of a virus into the vaccinated individual. These mRNA fragments are taken up by the dendritic cells, a component cell of the immune system. The dendritic cells use their own internal machinery (ribosomes) to read the mRNA and produce the viral antigens that the mRNA encodes. After production of the viral antigens, the foreign mRNA is destroyed. The viral antigens are presented to the immune system of the body, more specifically to the T and B cells of the system, in association with class l & ll MHC molecules. The activated T and B cells provide immunity to the body in the event of a future infection. Both the cellular and humeral immunity are stimulated.
Delivery of viable mRNA to the immune cells was a roadblock in the production of mRNA vaccines, since naked RNA is degraded by enzymes called RNAses, as part of the protective mechanisms of the body. With the discovery of lipid nanoparticles, that could encapsulate the mRNA molecule, a critical breakthrough was achieved in the production of viable mRNA vaccines. This solved a number of key technical barriers in delivering the mRNA molecule into the host cell. The lipid provides a layer of protection against degradation of mRNA. In addition, customization of the outer layer of the lipid nanoparticles allows the vaccine to target specific cell types in the body. The following types have been extensively evaluated:
PFIZER–BioNTech COVID-19 VACCINE:
The Pfizer–BioNTech COVID-19 vaccine (INN: tozinameran) is an mRNA-based COVID-19 vaccine. The vaccine is called BNT162b2. BioNTech, a German company, developed the vaccine and collaborated with Pfizer, an American company, for support with clinical trials and manufacturing. The vaccine is composed of nucleoside-modified mRNA (modRNA). It is given by intramuscular route and requires two doses, given three weeks apart. Distribution and storage is a logistical challenge because the vaccine needs to be stored at extremely low temperatures- between −80 and −60 °C (−112 and −76 °F), until five days before vaccination when it can be stored at 2 to 8 °C (36 to 46 °F), and up to two hours at temperatures up to 25 °C (77 °F) or 30 °C (86 °F). In February 2021, the U.S. (FDA) updated the emergency use authorization (EUA) to permit undiluted frozen vials of the vaccine to be transported and stored at between −25 and −15 °C (−13 and 5 °F) for up to two weeks before use.
It was initially authorized for use in people aged 16 years and older. On May 10, 2021 U.S. FDA (Food and Drug Administration) granted it EUA (Emergency Use Authorization) for those aged 12 to 15 years, after Pfizer and BioNTech announced on March 31, 2021, from initial phase lll trial data, that the vaccine was found to be 100% effective for this age group.
The efficacy of the vaccine against mild and moderate COVID-19, in candidates 16 years and older, is 95%. It was found to be 94% effective against COVID-19 hospitalization in fully vaccinated adults and 64% effective among partially vaccinated adults aged more than 65 years. Researchers reported in the New England Journal of Medicine and The Lancet that the Pfizer-BioNTech COVID-19 vaccine is extremely effective against two dangerous variants of SARS-CoV-2, the B.1.1.7 strain, first found in the United Kingdom and the B.1.351 (also called the 501.V2 variant) discovered in South Africa. The Pfizer vaccine was found to be 87 to 89.5 percent effective at preventing infection from the B.1.1.7 variant among those who were two weeks past their second dose and 72.1 to 75 percent effective against the B.1.351 variant. It was close to 100 percent effective at preventing severe, critical, or fatal cases of either variant.
The ongoing Phase III trial, that started in November 2020 and is scheduled to run till 2022, in addition to assessing safety, efficacy, tolerability, and immunogenicity of BNT162b2, is also designed to assess the ability of vaccine to prevent severe infection, as well as the duration of immune effect. Pfizer started a Phase II–III randomized control trial in healthy pregnant women 18 years of age and older. The first participants received their first dose in this trial in February.
MODERNA COVID-19 VACCINE:
The vaccine is codenamed mRNA-1273. It is approved for people aged 18 years and older and is administered by intramuscular route, as two doses, four weeks apart. It is an mRNA vaccine composed of nucleoside-modified mRNA (modRNA) encoding a spike protein of SARS-CoV-2. On March 15, 2021, Moderna’s second COVID-19 vaccine (mRNA-1283) started phase I clinical trials.
The vaccine has an efficacy of 94.1% against mild and moderate COVID-19 and a 100% efficacy against serious COVID-19, with or without hospitalization or death. According to early results from its booster shot trial, a third dose of the Moderna mRNA vaccine given six to eight months after the first two doses boosted antibodies to protect against the South African B.1.351 variant and the P1 variant (also known as 20J/501Y.V3) strain found in Brazil. Moderna is testing its original vaccine and a version modified to target the B.1.351/501.V2 variant.
Studies have started to assess efficacy and safety in children aged 0–11 (KidCOVE) and 12–17 (TeenCOVE). The duration of protection provided by the vaccine is not known as of April 2021, and a two-year study is underway to determine this.
The vaccine has a favorable safety profile with no safety concerns, according to WHO (World Health Organization). CDC (Centers for Disease Control and Prevention) has reported anaphylaxis (a severe and potentially serious allergic reaction) in 2.5 cases per million doses administered and has recommended a 15-minute observation period after injection. Though pregnant women were excluded from the initial trials, based on the results of a preliminary study, the CDC recommends that pregnant people get vaccinated with the COVID-19 vaccine.
VIRAL VECTOR VACCINES
The concept of creating viral vectors was started in the 1970s. Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. Other than their use in vaccines, viral vectors have also been studied for gene therapy, to treat cancer, and for molecular biology research.
In the COVID-19 viral vector vaccines, genetic material from the SARS-CoV-2 is inserted into a weakened live virus, such as an adenovirus. The weakened virus (viral vector) serves as a delivery system for the genetic material from the COVID-19 into the human cells it infects. Following vaccination, the adenovirus vector enters the cells and releases its genes, which are transported to the cell nucleus; thereafter the cellular machinery does the transcription into mRNA followed by translation into S (spike) proteins. That is, the newly delivered genetic material gives human cells instructions to make copies of the S protein. The S proteins thus made, are displayed on the cell surfaces. The immune system of the body responds to these foreign proteins by creating memory B cells, that are capable of producing antibodies against the spike proteins, and the memory T cells, that are capable of attacking cells infected with SARS-CoV-2. After being vaccinated against COVID-19, a future infection with the COVID-19 virus will result in augmented formation of antibodies and activated T cells that will fight the SARS-CoV-2.
Viral vectors themselves cannot cause infection with COVID-19 or an infection of their own, nor can the genetic material delivered by the viral vector integrate into a person’s DNA forever. Some of the important vaccines in this category, that have been approved and are being used, are:
ASTRAZENECA COVID-19 VACCINE:
The Oxford–AstraZeneca COVID-19 vaccine, codenamed AZD1222 has been developed in England. It is given by an intramuscular injection and uses the modified (replication deficient) chimpanzee adenovirus ChAdOx1 as the viral vector. The adenovirus is called replication-deficient because the genes required for replication were deleted and replaced by a gene coding for the spike protein. Presently it is being used for individuals 18 years and older.
The efficacy of the vaccine is 76.0% at preventing symptomatic COVID-19 beginning at 22 days following the first dose and 81.3% after the second dose. It is probably 80-90% efficacious against severe disease. Vaccine efficacy against symptomatic infection caused by the B.1.1.7 (UK variant) was 70.4%. The vaccine did not protect against mild to moderate infection with the B.1.351 (501.V2- South African) variant in a study in South Africa, published in the New England Journal of Medicine.
JOHNSON & JOHNSON’S JANSSEN COVID-19 VACCINE:
J&J vaccine was developed by Janssen Vaccines in Leiden, Netherlands, and its Belgian parent company Janssen Pharmaceuticals, subsidiary of American company Johnson & Johnson. It is a single dose vaccine and the viral vector used is the human adenovirus. It is recommended for persons 18 years and older. Results published in the New England Journal of Medicine showed that the J&J vaccine has an efficacy of 64% against moderate to severe disease and 82% against severe/critical disease, beginning 28 days post-vaccination, with the 501.V2 (South African) variant. With the P1 (Brazilian) variant, those figures were, respectively, 68% and 88%. In the U.S. population, the J&J vaccine had an efficacy of 72% in preventing moderate to severe COVID-19 and 85.9% in preventing severe or critical COVID-19.
It’s efficacy in preventing severe COVID-19 with hospitalization or death is close to 100%. The transportation and storage of the vaccine is easier since it does not need to be frozen
SPUTNIK V COVID-19 VACCINE:
Developed in Russia, Sputnik V uses recombinant adenovirus types 26 and 5 as vectors in the vaccine. These vectors contain the SARS-CoV-2 S protein cDNA. It is administered intramuscularly- the Ad26-based vaccine is used on the first day and the Ad5 vaccine is used on the 21st day to boost immune response. The vaccine can be formulated in two ways: as a ready-to-use solution, frozen at the common home-freezer temperature of −18 °C/0 °F or lower; and as a freeze-dried powder called “Gam-COVID-Vac-Lyo”, that can be stored at temperatures above freezing, 2 to 8 °C or 36 to 46 °F (at the common home-refrigerator temperature). The freeze-dried powder has to be reconstituted with water before use.
Interim results indicate that it has an efficacy of 91.6% (95% CI 85.6–95.2) after the second vaccination, based on its ability to prevent symptomatic infection. There were no cases of moderate or severe covid-19 in the vaccinated group at least 21 days following the first dose and there were no unusual side effects. An article published in The Lancet, May 12, pointed out some controversies and inconsistencies around the reporting of interim phase 3 trial data for Sputnik V.
This vaccine is also developed in Russia and is a single dose COVID-19 vaccine. It actually consists of the first dose of the Sputnik V vaccine, which is based on the Ad26 vector, and it can be stored at a normal refrigerator temperature of 2 to 8 °C (36 to 46 °F). According to Gamaleya Research Institute of Epidemiology and Microbiology, this version, with an effectiveness of 79.4%, is suited for areas with acute outbreaks, allowing more people to be vaccinated quickly.
AD5-nCOV, under the trade name of Convidecia, is a single-dose viral vector vaccine for COVID-19, developed by CanSino Biologics (China). The vaccine has an efficacy of 65.7% in preventing moderate symptoms of COVID-19, and 91% efficacy in preventing severe disease.
INACTIVATED VIRAL COVID-19 VACCINES:
Inactivated COVID-19 vaccines use a more traditional technology similar to the one used for manufacturing inactivated polio vaccine. First, a sample of SARS-CoV-2 is used to grow large quantities of the virus using vero cells. Viruses from the culture are soaked in beta-propiolactone that deactivates them by binding to their genes, while leaving the other viral particles intact. The result is an inactivated virus that is then mixed with an aluminium-based adjuvant. Such inactivated SARS-CoV-2 particles lose their disease producing capacity, while still stimulating an immune response. Some of the important vaccines are:
This inactivated viral vaccine is produced in India. Complete vaccination consists of 2 doses, 4 weeks apart. Phase lll trials have shown an efficacy of 81% with 78% (61-88%) efficacy against mild or moderate disease and almost 100% efficacy against severe disease. Multiple ethical breaches have been reported at one of the trial sites at Bhopal, potentially jeopardizing the quality of overall data. No serious side effects have been reported so far. Preliminary In vitro studies with B.1.1.7 variant (UK variant) show Covaxin to be effective in neutralizing this strain. The Indian Council of Medical Research (ICMR) reported in April 2021 that the vaccine has also shown promising results in neutralizing the double mutant strain discovered in India- B.1.617.
This vaccine was developed in China. The immunization schedule consists of two doses with a 14-day interval. The vaccine and raw material for formulating the new doses can be transported and refrigerated at 2 to 8 °C (36 to 46 °F). One of the broadest real world studies published so far, for any of the vaccines used against SARS-CoV-2, are from Chile. The study indicated that the vaccine had an efficacy of 65% against symptomatic infection, reduced hospitalizations by 87%, intensive care visits by 90%, and deaths by 86%.
Efficacy results from Brazil, published by Sinovac (company that developed the vaccine), showed an efficacy of 50.65% (95% CI, 35.66–62.15%) against all symptomatic cases, 83.70% (57.99-93.67%) against cases that require medical treatment, and 100% (56.37-100%) against severe, hospitalized and fatal cases. In Brazil the vaccine was found to be efficient against three variants of COVID-19- British B.1.1.7, South African 501.V2, and Brazil B.1.1.28.
Phase III results from Turkey showed an efficacy of 84%. The vaccine prevented hospitalization and severe illness in 100% of cases.
SINOPHARM BBIBP-CorV COVID-19 VACCINE:
Manufactured in China, this vaccine has a two dose immunization schedule with an efficacy of 65-86% against mild to moderate disease and almost 100% efficacy against severe disease, with or without hospitalization. Results of its efficacy against the South African strain are variable.
Protein Subunit COVID-19 vaccines:
The vaccine is codenamed NVX-CoV2373. It is also called SARS-Cov2CrS (recombinant spike). It is a protein nanoparticle with Matrix-M1 adjuvant. It has been described as both a protein subunit vaccine and a virus-like particle vaccine, though the producers call it a recombinant nanoparticle vaccine. An engineered baculovirus, containing a gene for a modified SARS-CoV-2 spike protein, is made to infect a culture of Sf9 moth cells, which create the spike protein and display it on their cell membranes. The spike proteins are harvested and assembled onto a synthetic lipid nanoparticle, each displaying up to 14 spike proteins. The formulation includes a saponin based adjuvant. It requires two doses for complete immunization and is stable at 2 to 8 °C (36 to 46 °F).
The first human safety studies of the vaccine started in May 2020 in Australia. Presently it is undergoing trials in India under the brand name of Covovax. On 12 March 2021, Novavax announced that the vaccine was 96.4% effective in preventing the original strain of COVID-19 and 86% effective against the B.1.1.7. strain (UK variant). It proved 55% effective against the 501.V2 strain (South African variant) in people without HIV/AIDS. It was also 100% effective at preventing severe illness. As of 10 May 2021, the COVID-19 vaccine had not yet completed its US Phase III trials.
In total, as of March 2021, 308 vaccine candidates are in various stages of development, with 73 in clinical research, including 24 in Phase I trials, 33 in Phase I–II trials, and 16 in Phase III development.
SIDE EFFECTS OF COVID-19 VACCINES:
Some side effects, like a low-grade fever or muscle aches and pains, are common and not a cause for alarm. They are commonly observed after most vaccines and are not a cause of worry. They often resolve spontaneously.
These signs are an indication of the immune system responding to the antigen (a substance that triggers an immune response) in the vaccine and that it is gearing up to fight the virus. At the same time, experiencing no side effects does not mean that the vaccine is not working. This just means that everybody responds differently.
It is common practice to keep a person under observation for 15–30 minutes at the vaccination site after receiving vaccination so that health workers are available in case of any immediate reactions like anaphylaxis (severe allergic reaction), even though these have been observed very rarely. The vaccinated individuals are advised to alert their local health providers if they experience any unexpected side effects or other health events – such as side effects lasting more than three days. National authorities and international bodies, including WHO, are closely monitoring for any unexpected side effects following COVID-19 vaccine use.
Some of the side effects are as follows:
- AT THE SITE OF INJECTION: Pain, Soreness, Redness, and Swelling
- THROUGHOUT THE BODY: Fever, chills, muscle aches & pains, headache, tiredness, nausea. In rare cases allergic reactions, including anaphylaxis, can occur within a few minutes to one hour after receiving a dose. Therefore vaccines should be given under close supervision with appropriate medical treatment available.
SIDE EFFECTS UNIQUE TO DIFFERENT VACCINES:
AstraZeneca COVID-19 vaccine: Formation of blood clots has been observed, though very rarely, in patients who received the AstraZeneca COVID-19 vaccine. The symptoms related to blood clots were observed 4-20 days after the administration of vaccine. The reported incidence is 1 in 250,000 people vaccinated in Europe. The involved blood vessels are smaller than those affected by deep vein thrombosis that can occur on long plane flights. The clots form at uncommon anatomical sites, like brain and mesenteric blood vessels, in combination with low levels of blood platelets. This has come to be known as Thrombosis with Thrombocytopenia Syndrome, or TTS.
Janssen by Johnson & Johnson: Formation of blood clots has also been noted as an extremely rare side effect of J&J vaccine. The clots form within one to two weeks following vaccination. The pathophysiology appears to be the same as for AstraZeneca vaccine related blood clots.
The Centers for Disease Control and Prevention (CDC), United States, identified a total of 28 cases of serious, potentially life-threatening blood clots among the more than 8.7 million people who have received the Johnson & Johnson COVID-19 vaccination. Out of the 28 cases identified, only six were found in men. According to CDC, the overall rate of occurrence is about 7 per 1 million vaccinated women between 18 and 49 years old. For women 50 years and older and men of all ages, this adverse event is even more rare.
There have been no confirmed reported cases of TTS after the 135 million Pfizer doses or the 110 million Moderna doses administered in the U.S.
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