Issue Date: 29 January 2021 (sheet of 12); 31 March 2021 (sheet of 6)
Designer: Inter-Governmental Philatelic Corporation
Sheet Composition: 12 x 400 FCFA; 5 x 660 FCFA + 1 label
Printing Method: Offset lithography
Printer: Inter-Governmental Philatelic Corp., Brooklyn NY, U.S.A.
Although this edition is authorized by the Central African Republic Postal Administration, it was not sold in the Central Africa Republic, but only distributed to the novelty trade by the Inter-Governmental Philatelic Corporation based in Brooklyn, New York.
A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID‑19). The COVID‑19 vaccines are widely celebrated for their role in reducing the spread, severity, and death caused by COVID-19. Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine technologies during early 2020. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19.
In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. As of June 2021, 18 vaccines are authorized by at least one national regulatory authority for public use: two RNA vaccines (Pfizer–BioNTech and Moderna), nine conventional inactivated vaccines (BBIBP-CorV, Chinese Academy of Medical Sciences, CoronaVac, Covaxin, CoviVac, COVIran Barakat, Minhai-Kangtai, QazVac, and WIBP-CorV), five viral vector vaccines (Sputnik Light, Sputnik V, Oxford–AstraZeneca, Convidecia, and Johnson & Johnson), and two protein subunit vaccines (EpiVacCorona and RBD-Dimer). 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.
Many countries have implemented phased distribution plans that prioritize those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers. Single dose interim use is under consideration to extend vaccination to as many people as possible until vaccine availability improves.
As of 20 June 2021, 2.66 billion doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies. AstraZeneca anticipates producing 3 billion doses in 2021, Pfizer–BioNTech 1.3 billion doses, and Sputnik V, Sinopharm, Sinovac, and Johnson & Johnson 1 billion doses each. Moderna targets producing 600 million doses and Convidecia 500 million doses in 2021. By December 2020, more than 10 billion vaccine doses had been preordered by countries, with about half of the doses purchased by high-income countries comprising 14% of the world’s population.
Prior to COVID‑19, a vaccine for an infectious disease had never been produced in less than several years – and no vaccine existed for preventing a coronavirus infection in humans. However, vaccines have been produced against several animal diseases caused by coronaviruses, including (as of 2003) infectious bronchitis virus in birds, canine coronavirus, and feline coronavirus. Previous projects to develop vaccines for viruses in the family Coronaviridae that affect humans have been aimed at severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Vaccines against SARS and MERS have been tested in non-human animals.
According to studies published in 2005 and 2006, the identification and development of novel vaccines and medicines to treat SARS was a priority for governments and public health agencies around the world at that time. As of 2020, there is no cure or protective vaccine proven to be safe and effective against SARS in humans. There is also no proven vaccine against MERS. When MERS became prevalent, it was believed that existing SARS research might provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection. As of March 2020, there was one (DNA-based) MERS vaccine which completed Phase I clinical trials in humans, and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA-vectored (MVA-MERS-S).
Since January 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.
Multiple steps along the entire development path are evaluated, including:
- the level of acceptable toxicity of the vaccine (its safety),
- targeting vulnerable populations,
- the need for vaccine efficacy breakthroughs,
- the duration of vaccination protection,
- special delivery systems (such as oral or nasal, rather than by injection),
- dose regimen,
- stability and storage characteristics,
- emergency use authorization before formal licensing,
- optimal manufacturing for scaling to billions of doses, and
- dissemination of the licensed vaccine.
In February 2020, the WHO said it did not expect a vaccine against SARS‑CoV‑2 to become available in less than 18 months. The rapidly growing infection rate of COVID‑19 worldwide during early 2020 stimulated international alliances and government efforts to urgently organize resources to make multiple vaccines on shortened timelines, with four vaccine candidates entering human evaluation in March.
On 24 June 2020, China approved the CanSino vaccine for limited use in the military, and two inactivated virus vaccines for emergency use in high-risk occupations. On 11 August 2020, Russia announced the approval of its Sputnik V vaccine for emergency use, though one month later only small amounts of the vaccine had been distributed for use outside of the phase 3 trial.
The Pfizer–BioNTech partnership submitted an EUA request to the FDA for the mRNA vaccine BNT162b2 (active ingredient tozinameran) on 20 November 2020. On 2 December 2020, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory approval for the Pfizer–BioNTech vaccine, becoming the first country to approve this vaccine and the first country in the Western world to approve the use of any COVID‑19 vaccine. As of 21 December, many countries and the European Union had authorized or approved the Pfizer–BioNTech COVID‑19 vaccine. Bahrain and the United Arab Emirates granted emergency marketing authorization for BBIBP-CorV, manufactured by Sinopharm. On 11 December 2020, the United States Food and Drug Administration (FDA) granted an Emergency Use Authorization (EUA) for the Pfizer–BioNTech COVID‑19 vaccine. A week later, they granted an EUA for mRNA-1273, the Moderna vaccine.
On 31 March 2021, the Russian government announced that they had registered the first COVID-19 vaccine for animals. Named Carnivac-Cov, it is an inactivated vaccine for carnivorous animals, including pets, aimed at preventing mutations that occur during the interspecies transmission of SARS-CoV-2.
In June 2021, a report revealed that the UB-612 vaccine, developed by the US-based COVAXX, was a venture initiated for profits by the Blackwater founder Erik Prince. In a series of text messages to Paul Behrends, the close associate recruited for the COVAXX project, Prince described the profit-making possibilities in selling the Covid-19 vaccines. COVAXX provided no data from the clinical trials on safety or efficacy. The responsibility of creating distribution networks was assigned to an Abu Dhabi-based entity, which was mentioned as “Windward Capital” on the COVAXX letterhead but was actually Windward Holdings. The sole shareholder of the firm, which handled “professional, scientific and technical activities”, was Erik Prince. In March 2021, COVAXX raised $1.35 billion in a private placement.
As of January 2021, nine different technology platforms – with the technology of numerous candidates remaining undefined – are under research and development to create an effective vaccine against COVID‑19. Most of the platforms of vaccine candidates in clinical trials are focused on the coronavirus spike protein and its variants as the primary antigen of COVID‑19 infection. Platforms being developed in 2020 involved nucleic acid technologies (nucleoside-modified messenger RNA and DNA), non-replicating viral vectors, peptides, recombinant proteins, live attenuated viruses, and inactivated viruses.
Many vaccine technologies being developed for COVID‑19 are not like vaccines already in use to prevent influenza, but rather are using “next-generation” strategies for precise targeting of COVID‑19 infection mechanisms. Several of the synthetic vaccines use a 2P mutation to lock the spike protein into its prefusion configuration, stimulating an immune response to the virus before it attaches to a human cell. Vaccine platforms in development may improve flexibility for antigen manipulation, and effectiveness for targeting mechanisms of COVID‑19 infection in susceptible population subgroups, such as healthcare workers, the elderly, children, pregnant women, and people with weakened immune systems.
An RNA vaccine contains RNA which, when introduced into a tissue, acts as messenger RNA (mRNA) to cause the cells to build the foreign protein and stimulate an adaptive immune response which teaches the body how to identify and destroy the corresponding pathogen or cancer cells. RNA vaccines often, but not always, use nucleoside-modified messenger RNA. The delivery of mRNA is achieved by a coformulation of the molecule into lipid nanoparticles which protect the RNA strands and help their absorption into the cells.
RNA vaccines were the first COVID-19 vaccines to be authorized in the United Kingdom, the United States and the European Union. As of January 2021, authorized vaccines of this type were the Pfizer–BioNTech COVID-19 vaccine and the Moderna COVID-19 vaccine. As of February 2021, the CVnCoV RNA vaccine from CureVac was awaiting authorization in the EU.
Severe allergic reactions are rare. In December 2020, 1,893,360 first doses of Pfizer–BioNTech COVID‑19 vaccine administration resulted in 175 cases of severe allergic reaction, of which 21 were anaphylaxis. For 4,041,396 Moderna COVID-19 vaccine dose administrations in December 2020 and January 2021, only ten cases of anaphylaxis were reported. The lipid nanoparticles were most likely responsible for the allergic reactions.
Adenovirus Vector Vaccines
These vaccines are examples of non-replicating viral vector vaccines, using an adenovirus shell containing DNA that encodes a SARS‑CoV‑2 protein. The viral vector-based vaccines against COVID-19 are non-replicating, meaning that they do not make new virus particles, but rather produce only the antigen which elicits a systemic immune response.
As of January 2021, authorized vaccines of this type were the Oxford–AstraZeneca COVID-19 vaccine, the Sputnik V COVID-19 vaccine, Convidecia, and the Johnson & Johnson COVID-19 vaccine.
Convidecia and the Johnson & Johnson COVID-19 vaccine are both one-shot vaccines which offer less complicated logistics and can be stored under ordinary refrigeration for several months.
The Sputnik V COVID-19 vaccine uses Ad26 for the first dose, which is the same as the Johnson & Johnson vaccine’s only dose, and Ad5 for the second dose. Convidecia uses Ad5 for its only dose.
Inactivated Virus Vaccines
Inactivated vaccines consist of virus particles that have been grown in culture and then are killed using a method such as heat or formaldehyde to lose disease producing capacity, while still stimulating an immune response.
As of January 2021, authorized vaccines of this type were the Chinese CoronaVac, BBIBP-CorV, and WIBP-CorV; the Indian Covaxin; and the Russian CoviVac. Vaccines in clinical trials included the Valneva COVID-19 vaccine.
Subunit vaccines present one or more antigens without introducing whole pathogen particles. The antigens involved are often protein subunits, but can be any molecule that is a fragment of the pathogen.
As of April 2021, the two authorized vaccines of this type were the peptide vaccine EpiVacCorona and RBD-Dimer. Vaccines with pending authorizations included the Novavax COVID-19 vaccine, Soberana 02 (a conjugate vaccine), and the Sanofi–GSK vaccine. The V451 vaccine was previously in clinical trials, which were terminated because it was found that the vaccine may potentially cause incorrect results for subsequent HIV testing.
Additional types of vaccines that are in clinical trials include virus-like particle vaccines, multiple DNA plasmid vaccines, at least two lentivirus vector vaccines, a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.
Oral vaccines and intranasal vaccines are being developed and studied.
Scientists investigated whether existing vaccines for unrelated conditions could prime the immune system and lessen the severity of COVID‑19 infection. There is experimental evidence that the BCG vaccine for tuberculosis has non-specific effects on the immune system, but no evidence that this vaccine is effective against COVID‑19.
The Pfizer–BioNTech COVID-19 vaccine, sold under the brand name Comirnaty, is an mRNA-based COVID-19 vaccine developed by the German company BioNTech. It is authorized for use in people aged 12 years and older in some jurisdictions and for people 16 years and older in other jurisdictions, to provide protection against infection by the SARS-CoV-2 virus, which causes COVID-19. For its development BioNTech collaborated with Pfizer, an American company, for support with clinical trials, logistics, and manufacturing. In China, BioNTech is partnered with China-based Fosun Pharma for development, marketing, and distribution rights and the vaccine is colloquially described as the Fosun–BioNTech COVID‑19 vaccine. The vaccine is given by intramuscular injection. It is composed of nucleoside-modified mRNA (modRNA) encoding a mutated form of the full-length spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles. Vaccination requires two doses given three weeks apart.
Clinical trials began in April 2020; by November 2020, the vaccine entered Phase III clinical trials, with over 40,000 people participating. An interim analysis of study data showed a potential efficacy of 91.3% in preventing infection within seven days of a second dose. The most common side effects include mild to moderate pain at the injection site, fatigue, and headaches. Reports of serious side effects, such as allergic reactions, are very rare; no long-term complications have been reported. Monitoring of the primary outcomes from the trials will continue until August 2021, while monitoring of the secondary outcomes will continue until January 2023.
The vaccine was the first COVID‑19 vaccine to be authorized by a stringent regulatory authority for emergency use and the first cleared for regular use.In December 2020, the United Kingdom was the first country to authorize its use on an emergency basis. It is authorized for use at some level in 84 countries including the United States and Canada, countries in the European Union, the United Kingdom, Australia, Ukraine, Israel, Brazil, Bangladesh, Mexico, Japan and Singapore.
As of 30 March 2021, Pfizer and BioNTech aimed to manufacture about 2.5 billion doses in 2021. BioNTech and Pfizer have advance purchase agreements of about US$3 billion to provide a licensed vaccine in the United States, the European Union, the United Kingdom, Japan, Canada, Peru, Singapore and Mexico. Distribution and storage is a logistical challenge because the vaccine needs to be stored at extremely low temperatures. BioNTech and Pfizer are testing a freeze-dried version that would not need ultracold storage.
The Moderna COVID‑19 vaccine, codenamed mRNA-1273, is a COVID-19 vaccine developed by Moderna, the United States National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA). It is used in people aged 18 years and older to provide protection against infection by the SARS-CoV-2 virus, which causes COVID-19. It is designed to be administered as two 0.5 mL doses given by intramuscular injection at an interval of four weeks apart.
It is an RNA vaccine composed of nucleoside-modified mRNA (modRNA) encoding a spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles.
The Moderna COVID‑19 vaccine is authorized for use at some level in 53 countries including the United States, Canada, the European Union, the United Kingdom, Israel, and Singapore.
In January 2020, Moderna announced development of an RNA vaccine, codenamed mRNA-1273, to induce immunity to SARS-CoV-2. Moderna’s technology uses a nucleoside-modified messenger RNA (modRNA) compound codenamed mRNA-1273. Once the compound is inside a human cell, the mRNA links up with the cell’s endoplasmic reticulum. The mRNA-1273 is encoded to trigger the cell into making a specific protein using the cell’s normal manufacturing process. The vaccine encodes a version of the spike protein with a modification called 2P, in which the protein includes two stabilizing mutations in which the original amino acids are replaced with prolines, developed by researchers at the University of Texas at Austin and the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center. Once the protein is expelled from the cell, it is eventually detected by the immune system, which begins generating efficacious antibodies. The mRNA-1273 drug delivery system uses a PEGylated lipid nanoparticle drug delivery (LNP) system.
On 15 March 2021, Moderna’s second COVID‑19 vaccine (mRNA-1283) started phase I clinical trials.
The Gamaleya Research Institute of Epidemiology and Microbiology (Russian: Национальный исследовательский центр эпидемиологии и микробиологии имени почётного академика Н. Ф. Гамалеи, romanized: Natsional’nyy isslyedovatyel’skiy tsentr epidyemiologii i mikrobiologii imyeni pochetnogo akadyemika N. F. Gamalyei), is a Russian medical-research institute headquartered in Moscow. The institute, founded in 1891 by Filipp Markovich Blyumental, has commemorated in its name (since 1949) the prominent Ukrainian, Russian and Soviet scientist Nikolay Fyodorovich Gamaleya (1859-1949), famed as a pioneer in microbiology and in vaccine research. As of 2020, it operates under the purview of the Ministry of Health of the Russian Federation.
In May 2020, the centre announced that it had developed a COVID-19 vaccine candidate. The project was funded by the Russian National Wealth Fund. A Phase I trial was completed on 18 June 2020 and Phase II was reported as completed in July 2020.
On 11 August 2020, the Russian President Vladimir Putin declared that the institute registered a COVID-19 vaccine called Gam-COVID-Vac.
Protest developed in the international scientific community over the announcement of the vaccine registration in Russia, mainly because there has been no publication of results from clinical trials on Gam-COVID-Vac. At the time of registration, there was no evidence for the safety, effective dose, biomarkers of an immune response, or efficacy against COVID-19 infection. As of 8 August 2020, no reputable scientific report on the Gam-COVID-Vac candidate had been published.
On 4 September 2020, data on 76 participants in the Phase I-II trial were published, indicating preliminary evidence of safety and an immune response. Days later, however, the results were challenged by 27 international vaccine scientists as being incomplete, suspicious, and unreliable, when identical data were reported for many of the trial participants.
On 2 February 2021, results of Phase III clinical trials involving 21 977 participants in Moscow were published in The Lancet, showing 91.6% efficacy of the vaccine, and therefore responding, even if with considerable delays, to previous criticism.
Bharat Biotech International Limited (BBIL) is an Indian multinational biotechnology company headquartered in Hyderabad, engaged in the drug discovery, drug development, manufacture of vaccines, bio-therapeutics, pharmaceuticals and health care products.
In April 2020, the company announced that they have partnered with US-based company FluGen and University of Wisconsin-Madison to develop a COVID-19 vaccine.
In May 2020, Indian Council of Medical Research’s (ICMR’s) National Institute of Virology approved and provided the virus strains for developing a fully indigenous COVID-19 vaccine. On 29 June 2020, the company got permission to conduct Phase 1 and Phase 2 clinical trials in India for a developmental COVID-19 vaccine named Covaxin, from the Drugs Controller General of India (DCGI), Government of India. The Central Drugs Laboratory (CDL) at Kasauli in Himachal Pradesh has been engaged in testing experimental batches of Bharat Biotech’s COVID-19 vaccine Covaxin on a priority basis. A total of 12 sites were selected by the Indian Council for Medical Research for Phase I and II randomized, double-blind and placebo-controlled clinical trials of vaccine candidate.
In September 2020, the company announced that it was going to manufacture the novel chimp-adenovirus, a single dose intranasal vaccine (codenamed BBV154) for COVID-19 being developed in collaboration with the Washington University School of Medicine in St Louis, Missouri. It is currently undergoing clinical trials.
As an inactivated vaccine, Covaxin uses a more traditional technology that is similar to the inactivated polio vaccine. Initially, a sample of SARS-CoV-2 was isolated by India’s National Institute of Virology and used to grow large quantities of the virus using vero cells. From then on, the viruses are soaked in beta-propiolactone, which deactivates them by binding to their genes, while leaving other viral particles intact. The resulting inactivated viruses are then mixed with an aluminum-based adjuvant.
On 6 December 2020, Bharat Biotech applied to the Drugs Controller General of India (DCGI), seeking emergency use authorization. It was the third firm after Serum Institute of India and Pfizer to apply under such provision. On 2 January 2021, the Central Drugs Standard Control Organization (CDSCO) recommended permission, which was granted the next day. Covaxin was to be used in a “clinical trial mode” i.e. the public vaccination drive was to be an open-label, single-arm clinical trial in itself. This emergency approval, granted without considering Phase III trial data concerning efficacy and safety, drew widespread criticism.
The vaccine was also approved for emergency use in Iran and Zimbabwe. Mauritius received its first commercial supply of Covaxin on 18 March 2021. Nepal granted EUA for Covaxin on 19 March. On 29 March 29 Paraguay received 100,000 doses of Covaxin. On 7 April Mexico gave emergency authorization for Covaxin. On 19 April Philippines granted EUA to Covaxin. Additionally, Covaxin was granted EUA in Guatemala, Nicaragua, Guyana, Venezuela and Botswana.
On 31 March, the Brazilian health regulator Anvisa rejected Bharat Biotech’s application for supplying Covaxin in the country due to non-compliance with manufacturing norms. Bharat Biotech stated that they would re-apply after meeting the requirements. On June 4, Anvisa approved exceptional imports of Covaxin, imposing conditions that restrict it mainly to healthy adults and limiting it to just 1% of the country’s population to manage the risks through control and supervision of side effects. Anvisa cited as main concerns the incomplete phase III study, a short 45-day follow-up, which should be 60 days to meet the international consensus, and a novel imidazoquinoline adjuvant that may increase the chance of developing an autoimmune disease.
Argentina has agreed to buy 10 million doses of Covaxin and administer them for their citizens.
A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material coding for a desired antigen into the recipient’s host cells. As of April 2021, six viral vector vaccines have been authorized in at least one country: four COVID-19 vaccines and two Ebola vaccines.
Viral vector vaccines use a modified version of one virus as a vector to deliver to a cell a nucleic acid coding for an antigen for another infectious agent. Viral vector vaccines do not cause infection with either the virus used as the vector, or the source of the antigen. The genetic material it delivers does not integrate into a person’s genome.
Viral vector vaccines enable antigen expression within cells and induce a robust cytotoxic T cell response, unlike subunit vaccines which only confer humoral immunity. Most viral vectors are designed to be incapable of replication because the necessary genes are removed.
Adenovirus vectors have the advantage of high transduction efficiency, transgene expression, and broad viral tropism, and can infect both dividing and non-dividing cells. A disadvantage is that many people have pre-existing immunity to adenoviruses due to previous exposure. Human adenovirus serotype 5 is often used because it can be easily produced in high titers.
As of April 2021, four adenovirus vector vaccines for COVID-19 have been authorized in at least one country:
- The Oxford–AstraZeneca vaccine uses the modified chimpanzee adenovirus ChAdOx1
- Sputnik V uses human adenovirus serotype 26 for the first shot and serotype 5 for the second.
- The Johnson & Johnson vaccine uses serotype 26.
- Convidecia uses serotype 5.
The Oxford–AstraZeneca COVID-19 vaccine, codenamed AZD1222, and sold under the brand names Covishield and Vaxzevria among others, is a viral vector vaccine for prevention of COVID-19. Developed by Oxford University and AstraZeneca, it is given by intramuscular injection, using as a vector the modified chimpanzee adenovirus ChAdOx1. 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. Another analysis showed that, for symptomatic COVID-19 infection after the second dose, the vaccine is 66% effective against the Alpha variant (lineage B.1.1.7), and 60% against the Delta variant (lineage B.1.617.2).
The vaccine has a good safety profile, with side effects including injection-site pain, headache, and nausea, all generally resolving within a few days. More rarely, anaphylaxis may occur (the UK Medicines and Healthcare products Regulatory Agency (MHRA) has 268 reports out of some 21.2 million vaccinations as of 14 April 2021). In very rare cases (around 1 in 100,000 people) the vaccine has been associated with an increased risk of blood clots in combination with low levels of blood platelets. According to the European Medicines Agency as of 4 April 2021, 222 cases of blood clots have been reported from the European Economic Area and the UK, where around 34 million people have received the vaccine.
On 30 December 2020, the vaccine was first approved for use in the UK vaccination programme, and the first vaccination outside of a trial was administered on 4 January 2021. The vaccine has since been approved by several medicine agencies worldwide, such as the European Medicines Agency (EMA), and the Australian Therapeutic Goods Administration, and was approved for an Emergency Use Listing by the World Health Organization (WHO). Some countries have limited its use to elderly people at higher risk for severe COVID-19 illness due to concerns over the very rare side effects of the vaccine in younger individuals.
he Oxford–AstraZeneca COVID‑19 vaccine is used to provide protection against infection by the SARS-CoV-2 virus in order to prevent COVID-19 in adults aged 18 years and older. The medicine is administered by two 0.5 ml doses injected intramuscularly into the deltoid muscle (upper arm) four to twelve weeks apart, with the WHO recommending the second is given 8 to 12 weeks after the first for optimum efficacy.
The most common side effects in the clinical trials were usually mild or moderate and got better within a few days after vaccination. Vomiting, diarrhoea, swelling, redness at the injection site and low levels of blood platelets occurred in less than 1 in 10 people. Enlarged lymph nodes, decreased appetite, dizziness, sleepiness, sweating, abdominal pain, itching and rash occurred in less than 1 in 100 people.
In very rare cases (around 1 in 100,000 people) the vaccine can lead to blood clots in combination with low levels of blood platelets. The UK MHRA as of 14 April 2021 report an overall case incidence of thromboembolic events with concurrent low platelets of 7.9 per million doses (less than 1 in 100,000 people). As with other vaccines, anaphylaxis and other allergic reactions are a known side effect of ADZ1222 that should be given under close supervision. The European Medicines Agency (EMA) has assessed 41 cases of anaphylaxis from around 5 million vaccinations in the United Kingdom.
Capillary leak syndrome is a possible side effect of the vaccine.
The Oxford University and AstraZeneca collaboration was seen as having the potential as being a low-cost vaccine with no onerous storage requirements. A series of events from AstraZeneca, including miscommunication, supply difficulties, reports of adverse effects, national rollout suspensions, and politics including the high-profile European Commission–AstraZeneca COVID-19 vaccine dispute, have been a public relations disaster, and in the opinion of one academic has led to increased vaccine hesitancy.
The vaccine remains a key component of the WHO backed COVAX (COVID-19 Vaccines Global Access) program, with the WHO, the EMA, and the MHRA continuing to state that the benefits of the vaccine outweigh any possible side effects.
CoronaVac, also known as the Sinovac COVID-19 vaccine, is an inactivated virus COVID-19 vaccine developed by the Chinese company Sinovac Biotech. It was Phase III clinical trialed in Brazil, Chile, Indonesia, the Philippines, and Turkey and relies on traditional technology similar to BBIBP-CorV and Covaxin, other inactivated-virus COVID-19 vaccines. CoronaVac does not need to be frozen and both the final product and the raw material for formulating CoronaVac can be transported refrigerated at 2–8 °C (36–46 °F), temperatures at which flu vaccines are kept.
A real-world study of millions of Chileans who received CoronaVac found it 65% effective against symptomatic COVID-19, 87% against hospitalization, 90% against ICU admissions, and 86% against deaths. In Indonesia, real world data from 128,290 healthcare workers showed 94% protection against symptomatic infection by the vaccine, beating results in clinical trials. In Brazil, after 75% of the population in Serrana, São Paulo received CoronaVac, preliminary results show deaths fell by 95%, hospitalizations by 86%, and symptomatic cases by 80%.
Phase III results from Brazil previously showed 50.7% efficacy at preventing symptomatic infections and 83.7% effective in preventing mild cases needing treatment. Efficacy against symptomatic infections increased to 62.3% with an interval of 21 days or more between the doses. Final Phase III results from Turkey announced on 3 March 2021 showed an efficacy of 84%.
Politicization, transparency issues and some incomplete trial data in Brazil contributed to a lack of trust in CoronaVac there.
CoronaVac is being used in vaccination campaigns in various countries in Asia, South America, North America, and Europe. By April 2021, Sinovac had a production capacity of 2 billion doses a year and had delivered 600 million total doses. It is currently being manufactured at several facilities in China and a facility in Thailand with planned overseas manufacture in Brazil in September 2021 and eventually in Egypt and Hungary.
On 1 June 2021, the World Health Organization (WHO) validated the vaccine for emergency use, by which time over 430 million doses of CoronaVac had already been administered globally.
As an inactivated vaccine like BBIBP-CorV and Covaxin, CoronaVac uses a more traditional technology that is similar to the inactivated polio vaccine. Initially, a sample of SARS-CoV-2 from China was used to grow large quantities of the virus using vero cells. From then on, the viruses are soaked in beta-propiolactone, which deactivates them by binding to their genes, while leaving other viral particles intact. The resulting inactivated viruses are then mixed with an aluminium-based adjuvant.
CoronaVac does not need to be frozen, and both the vaccine and raw material for formulating the new doses could be transported and refrigerated at 2–8 °C (36–46 °F), temperatures at which flu vaccines are kept. CoronaVac could remain stable for up to three years in storage, which might offer some advantage in vaccine distribution to regions where cold chains are not developed.
In February, Thailand approved emergency use and started its vaccination program on 27 February. As of May, Thailand had received 6 million doses with 3 million more outstanding.
On 18 June 2021, Reuters reported that more than 350 Indonesian doctors and medical workers out of 5,000 in Kudus have contracted the SARS-CoV-2 Delta variant despite being vaccinated with the CoronaVac, an infection rate of 7 percent. In response to this development, Griffith University epidemiologist Dicky Budiman questioned the effectiveness of the CoronaVac vaccine against the Delta variant.
BBIBP-CorV, also known as the Sinopharm COVID-19 vaccine, is one of two inactivated virus COVID-19 vaccines developed by Sinopharm’s Beijing Institute of Biological Products. It completed Phase III trials in Argentina, Bahrain, Egypt, Morocco, Pakistan, Peru, and the United Arab Emirates (UAE) with over 60,000 participants. BBIBP-CorV shares similar technology with CoronaVac and Covaxin, other inactivated virus vaccines for COVID-19. Its product name is SARS-CoV-2 Vaccine (Vero Cell), not to be confused with the similar product name of CoronaVac.
Peer-reviewed results published in JAMA of Phase III trials in United Arab Emirates and Bahrain showed BBIBP-CorV 78.1% effective against symptomatic cases and 100% against severe cases (21 cases in vaccinated group vs. 95 cases in placebo group). In December 2020, the UAE previously announced interim results showing 86% efficacy.
While mRNA vaccines like the Pfizer–BioNTech COVID-19 vaccine and Moderna COVID-19 vaccine showed higher efficacy of over 90%, those present distribution challenges for some nations as they require deep-freeze facilities and trucks. BIBP-CorV could be transported and stored at normal refrigerated temperatures.
BBIBP-CorV is being used in vaccination campaigns by certain countries in Asia, Africa, South America, and Europe. Sinopharm expects to produce one billion doses of BBIBP-CorV in 2021. By May, Sinopharm had supplied 200 million doses.
On 7 May 2021, the World Health Organization approved the vaccine for use in COVAX.
The other inactivated virus vaccine developed by Sinopharm is WIBP-CorV.
As an inactivated vaccine like CoronaVac and Covaxin, BBIBP-CorV uses a more traditional technology that is similar to the inactivated polio vaccine. Initially, a sample of SARS-CoV-2 from China capable of rapid multiplication was used to grow large quantities of the virus using vero cells. From then on, the viruses are soaked in beta-propiolactone, which deactivates them by binding to their genes, while leaving other viral particles intact. The resulting inactivated viruses are then mixed with an aluminium-based adjuvant.
Sputnik V (Russian: Спутник V) or Gam-COVID-Vac (Russian: Гам-КОВИД-Вак) is an adenovirus viral vector vaccine for COVID-19 developed by the Gamaleya Research Institute of Epidemiology and Microbiology. It is the world’s first registered combination vector vaccine for the prevention of COVID-19 to be registered on 11 August 2020 by the Russian Ministry of Health.
The ‘V’ in its name means ‘Victory over COVID-19’ according to Kirill Dmitriev, CEO of Russian Direct Investment Fund .
Gam-COVID-Vac was initially approved for distribution in Russia and then in 59 other countries (as of April 2021) on the preliminary results of Phase I–II studies eventually published on 4 September 2020. Approval in early August of Gam-COVID-Vac was met with media criticism in mass media and discussions in the scientific community as to whether approval was justified in the absence of robust scientific research confirming safety and efficacy. On 2 February 2021, an interim analysis from the trial was published in The Lancet, indicating 91.6% efficacy without unusual side effects.
Emergency mass-distribution of the vaccine began in December 2020 in countries including Russia, Argentina, Belarus, Hungary, Serbia and the United Arab Emirates. By February 2021 over a billion doses of the vaccine had been ordered for immediate distribution worldwide.
Gam-COVID-Vac is a viral two-vector vaccine based on two human adenoviruses – a common cold virus – containing the gene that encodes the full-length spike protein (S) of SARS-CoV-2 to stimulate an immune response. The Gam-COVID-Vac vaccine was developed by a cellular microbiologists team of the government-backed Gamaleya Research Institute of Epidemiology and Microbiology. The group was led by MD and RAS associate member Denis Logunov, who also worked on vaccines for the Ebolavirus and the MERS-coronavirus.
The recombinant adenovirus types 26 and 5 are both used as vectors in the vaccine. They were biotechnology-derived and contain the SARS-CoV-2 S protein cDNA. Both of them are administered into the deltoid muscle: the Ad26-based vaccine is used on the first day and the Ad5 vaccine is used on the 21st day to boost immune response.
Both Ad26 and Ad5 were modified to remove the E1 gene to prevent replication. Large quantities of both adenoviruses are then produced by HEK 293 cells that have the E1 gene necessary for viral replication. Rarely, Ad5 can acquire the E1 gene from the HEK 293 cells, restoring its ability to replicate. Gamaleya has set an acceptable limit of 5,000 replicating virus particles per vaccine dose, and quality control documents state that tested batches contain less than 100 replicating virus particles per dose.
The vaccine can be formulated in two ways: as a ready-to-use solution in water that is frozen at the common home-freezer storage temperature of −18 °C or 0 °F or lower; and as a freeze-dried powder, “Gam-COVID-Vac-Lyo”, whose storage temperature is above freezing, 2–8 °C or 36–46 °F, at the common home-refrigerator temperature. The freeze-dried powder must be reconstituted with water before use.
The production of the frozen liquid formulation was developed for large-scale use, it is cheaper and easier to manufacture.
The production of the freeze-dried formulation takes much more time and resources, although it is more convenient for storage and transportation. It was developed with vaccine delivery to hard-to-reach regions of Russia in mind.
The head of the Gamaleya Research Institute Alexander Ginzburg estimates that it will take 9–12 months to vaccinate the vast majority of the Russian population, assuming in-country resources are adequate.
Sputnik-Light, a single-dose version, is also being developed to speed up vaccination outside Russia. It will offer less protection than the two-dose versions, but it is still expected to reach an efficacy of 85%.
Vaccine efficacy is the risk of getting the disease by vaccinated participants in a controlled trial compared with the risk of getting the disease by unvaccinated participants. An efficacy of 0% means that the vaccine does not work (identical to placebo). An efficacy of 50% means that there are half as many cases of infection as in unvaccinated individuals.
It is not straightforward to compare the efficacies of the different vaccines because the trials were run with different populations, geographies, and variants of the virus. In the case of COVID‑19, a vaccine efficacy of 67% may be enough to slow the pandemic, but this assumes that the vaccine confers sterilizing immunity, which is necessary to prevent transmission. Vaccine efficacy reflects disease prevention, a poor indicator of transmissibility of SARS‑CoV‑2 since asymptomatic people can be highly infectious. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) set a cutoff of 50% as the efficacy required to approve a COVID‑19 vaccine. Aiming for a realistic population vaccination coverage rate of 75%, and depending on the actual basic reproduction number, the necessary effectiveness of a COVID-19 vaccine is expected to need to be at least 70% to prevent an epidemic and at least 80% to extinguish it without further measures, such as social distancing.
In efficacy calculations, symptomatic COVID-19 is generally defined as having both a positive PCR test and at least one or two of a defined list of COVID-19 symptoms, although exact specifications vary between trials. The trial location also affects the reported efficacy because different countries have different prevalences of SARS-CoV-2 variants. Ranges below are 95% confidence intervals unless indicated otherwise, and all values are for all participants regardless of age, according to the references for each of the trials. By definition, the absence of a confidence interval means that the accuracy of the estimates without an associated confidence interval is unknown to the public. Efficacy against severe COVID-19 is the most important, since hospitalizations and deaths are a public health burden whose prevention is a priority.
The real-world studies of vaccine effectiveness measure to which extent a certain vaccine has succeeded in preventing COVID-19 infection, symptoms, hospitalization and death for the vaccinated individuals in a large population under routine conditions that are less than ideal.
The interplay between the SARS-CoV-2 virus and its human hosts was initially natural but is now being altered by the prompt availability of vaccines. The potential emergence of a SARS-CoV-2 variant that is moderately or fully resistant to the antibody response elicited by the current generation of COVID-19 vaccines may necessitate modification of the vaccines. Trials indicate many vaccines developed for the initial strain have lower efficacy for some variants against symptomatic COVID-19.