Baltina D. Watt MSc, MLS (ASCPi)
Medical Laboratory Professional
Address: PO Box 1632, Roseau, Commonwealth of Dominica
Email: [email protected]
Key terms: Vaccine, COVID-19, MERS, SARS, WHO, COVAX, clinical trials, vaccine efficacy, vaccinations, variants
Copyright: This is an open-access article under the terms of the Creative Commons Attribution License which permits use, distribution, and reproduction in any medium, provided the original work is properly cited.
©2021 The Authors. Caribbean Medical Journal published by Trinidad & Tobago Medical Association.
The novel Coronavirus disease 2019 (COVID-19), which was deemed a pandemic in March of 2020, brought about an unprecedented turn of events. A “new normal” phenomenon emerged where online schooling, telecommuting, closed ports, mandatory testing of travelers, social distancing, curfews and mask-wearing became commonplace. Numerous countries suffered economically due to precautionary measures taken to alleviate the spread of COVID-19. Moreover, daily reports continually relay increasing COVID-19 cases and the escalating death toll, consisting of the young, old, and even countless health professionals. To date, there have been over 100 million cases in approximately 220 countries, and roughly 2.4 million deaths.1,2 In the Caribbean, despite having relatively low COVID-19-related deaths, we have not fully escaped the pangs of this pandemic. The Caribbean Public Health Agency (CARPHA) reported 462,116 confirmed cases from 35 Caribbean countries or territories, and 6,726 deaths, with most of these cases coming from non-CARPHA member states. 3
Overarching consequences of the COVID-19 outbreak led to an accelerated and joint approach by the international community in an effort to combat it. Despite the intensive search for an efficacious therapeutic agent, no major breakthrough ensued. Hydroxychloroquine and remdesivir have been advocated as suitable treatments based on some inconclusive studies, yet there was still a need for a more effective means of therapy – at least 95%, in terminating this pandemic, thereby allowing us to regain normalcy.4,5 Resultantly, the most plausible option seemed to be an effective and safe COVID-19 vaccine, since vaccination has brought about major breakthroughs in disease outbreaks, and even complete eradication, as in the case of small pox. Consequently, COVAX – the COVID-19 vaccines global access facility, was established in April 2020 under the leadership of Gavi – the Vaccine Alliance, the Coalition for Epidemic Preparedness Innovations (CEPI) and the WHO (World Health Organization). This alliance ensured a quick response to this pandemic in terms of diagnostics and vaccine development, as well as worldwide access to such, regardless of countries’ economic conditions.6 This paper serves to provide a brief overview of COVID-19 vaccine development, with reference to previous coronavirus outbreaks, chiefly the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS).
COVID-19, MERS and SARS Explained
COVID-19 is caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), belonging to the group of Coronaviruses (CoVs), the family of Coronaviridae and genus of Betacoronaviruses. CoVs are single-stranded RNA viruses encased in an icosahedral (having 20 faces) protein shell. They possess numerous protruding club-like proteins on their surface that give a crown-like (corona) appearance when examined via electron microscopy.7 They possess four structural proteins – spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins.8 Seven CoVs are infectious to humans, but only three are considered to be highly pathogenic – SARS-CoV, which causes SARS, MERS-CoV, which causes MERS, and SARS-CoV-2.8 Studies on these CoVs confirm their numerous similarities. For instance, the SARS-CoV-2 genome shares 79% and 50% sequence identity with SARS-CoV and MERS-CoV genomes, respectively.9 Moreover, Wang et al. found that immunologic structures (epitopes) in SARS-CoV, like the S protein, are highly conserved in SARS-CoV-2 and have the potential to evoke cellular adaptive immune responses, and are excellent targets for vaccine development.10 Furthermore, the CoVs use angiotensin-converting enzyme 2 (ACE-2) receptors for cellular entry; however, the propensity of SARS-CoV-2 to attach to these receptors is much higher.11 Other similarities among these CoVs include, the fact that they utilise animal reservoirs – chiefly bats, though their intermediate hosts vary, and they portray similar clinical manifestations – including but not limited to fever, dry cough, sore throat and dyspnea.
SARS originated in Guangdong, China, in 2002, while COVID-19 originated in Wuhan, China, in 201910,12. SARS affected over 26 countries globally, with 8000 cases and almost 800 deaths.12 MERS emerged in Saudi Arabia in 2012, affecting 27 countries globally with a mortality rate of 35%.13 COVID-19 unquestionably has more far-reaching consequences and casualties than MERS and SARS combined. Consequently, COVID-19 is deemed as a Research and Development (R&D) Blueprint priority disease by the WHO as it poses major public health risk, and is considered a Public Health Emergency of International Concern (PHEIC). Substantial research is therefore being conducted on numerous COVID-19 vaccines, and quite a few have not only been approved for distribution, but have been administered globally.14 Owing to the similarities of the three CoVs, valuable data was acquired from the development of MERS and SARS vaccines, which no doubt aided in expediting COVID-19 vaccine development.15
What are Vaccines?
Vaccines are medical preparations, ranging from intact organisms (live-attenuated or inactivated) to genetically engineered parts of the organisms (antigenic – DNA, RNA, protein subunit, vectored and viral-like particles) that induce humoral and cellular adaptive immune responses. They stimulate sufficient memory T lymphocytes (T cells) and B lymphocytes (B cells) in response to pathogens, without causing disease.16 Moreover, upon exposure to pathogens one is vaccinated against, antibodies produced by B cells ought to be neutralising –coating the pathogen, thus preventing infection; whilst T cells contrastingly, kill infected cells directly. 16,17 Historically, live-attenuated vaccines tend to induce stronger immune responses than inactivated ones, however. Other essential factors to consider for vaccine development, include: the pathogen’s biological makeup, the eventual waning of immune responses – thus determining if booster shot(s) are required, the nature of the antigen utilised, antigenic mutations, chances of reinfection, and vaccine efficacy.17 Vaccine efficacy is a measure that compares the rates of disease between vaccinated and unvaccinated people in controlled clinical trials.18 Furthermore, vaccines typically contain immune boosters (adjuvants) like aluminum salts or lipids, stabilisers like sugar or gelatin, antibiotics, preservatives, inactivating agents like formaldehyde and may contain residual cell culture materials such as egg protein. Adverse reactions to vaccines occur in individuals with allergies to some vaccine ingredients.19
COVID-19 Vaccines Explained
Covid-19 vaccines are much more diverse in nature than the different vaccine platforms in the clinical trials against SARS and MERS, which primarily used the whole virion or S gene; however, all are dominated by the same antigens.9 As of February 14, 2021, WHO declared that 66 COVID-19 vaccine candidates were under clinical evaluation, and 176 were in preclinical evaluation.20,21 Table 1 outlines a range of COVID-19 vaccines at their varied stages of development and/or distribution. Greater success has been achieved with the mRNA vaccines like Pfizer’s and Moderna’s and non-replicating viral vaccines like Oxford-AstraZeneca’s, than with the other vaccine platforms. Yet the stringent storage conditions for the Pfizer vaccine complicates its distribution and administration. It should also be noted that these vaccines have not been tested on or approved for individuals below the age of 18, or 16, in the case of Pfizer’s vaccine. Nevertheless, vaccine trials are underway to test the Oxford-AstraZeneca vaccine in children as young as 6 years in the United Kingdom, whilst Moderna and Pfizer are to be tested on children ages 12-17 and 12-15 respectively, in the United States.22,23
Vaccine development is an arduous process that typically takes years to produce a viable vaccine. Firstly, vaccines are tested in appropriate animal models to see whether they are protective. Secondly, vaccines are tested for toxicity in animals, and this typically takes 3–6 months.9 For some vaccine platforms, parts of the safety testing might be skipped if there is already sufficient data available for similar vaccines made in the same production process. These steps formulate the pre-clinical stages of vaccine development. Once sufficient pre-clinical data is available and initial batches of the vaccine have been produced, of good manufacturing quality, clinical trials may be initiated.15
Clinical development of vaccines starts with small phase I trials to evaluate the safety of vaccine candidates in humans. These are followed by phase II trials (formulation and doses are established to prove efficacy) and finally by phase III trials, where the efficacy and safety of a vaccine need to be demonstrated in a larger cohort.15 Nonetheless, in an extraordinary situation like COVID-19, this scheme might be compressed and an accelerated regulatory approval pathway might be developed. If efficacy is shown, a vaccine might be licensed by regulatory agencies. Finally, it is time-consuming to distribute and administer vaccines. To vaccinate a large proportion of the population would likely take weeks or months, and booster doses might be needed, and are administered 3–4 weeks after the initial dose. It is likely that protective immunity will be achieved only 1–2 weeks after the second vaccinations, adding another 1–2 months to the timeline.15,19
Table 1. Representation of selected COVID-19 vaccine candidates
|Vaccine||Platform||Developer||Status||Administration and Storage||Efficacy*||Refs|
|BioNTech + Fosun Pharma; Jiangsu Provincial Center for Disease Prevention and Control + Pfizer
|Approved in US, UK, Australia, Canada, Latin America, Belgium, EU & Middle East||2 IM doses of 30µg, 3-4 weeks apart; stored at –70°C||95%||21, 24,25,27,28
|Moderna + National Institute of Allergy and Infectious Diseases
|Approved in US, Canada, EU, UK||2 IM doses of 100µg, 4 weeks apart; stored at –20°C||92%||21, 25 26,27,28
|VVnr- adenoviruses (rAd26-S+rAd5-S) + gene encoding S protein
|Gamaleya Research Institute; Health Ministry of the Russian Federation
|Phase 3 Clinical Trial – Russia, the UAE, India, Venezuela Belarus and Argentina||2 0.5ml IM doses 21 days apart; lyophilized form stored at 2-8°C||91.4%||21, 27,28,29|
|Oxford-AstraZeneca ChAdOx1-S (AZD1222) (Covishield)||VVnr (ChAd) + gene encoding S protein
|AstraZeneca + University of Oxford
|Approved in UK, India, Germany||2 IM doses of ~5×1010 viral particles 4 weeks to 3 months apart; stored at 2-8°C up to 6 months||62-70%||21,27,28
|mRNA (S protein) + LNP||CureVac||Phase 3 Clinical Trial – Germany||2 12µg IM doses, 4 weeks apart; stored at 2-5°C up to at least 3 months||N/A||21,27|
|Inactivated SARS-CoV-2||Sinovac||Approved in China and Indonesia
Phase 3 Clinical Trial – Brazil, Turkey
|2 IM doses, 2 weeks apart; stored at 2-8°C||91.25%||21,27,28|
|Sinopharm and Beijing Institute of Biological Products Co. Ltd||Approved in China, UAE, Bahrain and Egypt**||2 IM doses, 3 weeks apart;||79-86%||21,27,28|
|VVnr (Ad26)||Janssen Pharmaceutical (Johnson&Johnson)||Phase 3 Clinical Trial – US||1 dose or 2 doses, 2 months apart; stored at –20°C up to 2 years||N/A||21,27|
|NVX-CoV2373||PS – recombinant S protein nanoparticle + MatrixM as adjuvant
|Phase 3 Clinical Trial – US, UK and Mexico||2 IM doses, each containing 5µg of protein and 50µg of adjuvant, 3 weeks apart; stored at 2-8°C||N/A||21,27
|INO-4800||Plasmid DNA encoding S protein and delivered by electroporation||Inovio Pharmaceuticals + International Vaccine Institute + Advaccine (Suzhou) Biopharmaceutical Co., Ltd||Phase 3 Clinical Trial – US,
Phase 2 Clinical Trial – China
|2 1.0mg or 2.0mg ID doses, 4 weeks apart||N/A||21,27
|COVI-VAC||LAV||Codagenix/Serum Institute of India
|Phase 1 Clinical Trial – UK||1 IN dose; can be stored at 2-8°C||N/A||21
|COVID-19 Vaccine||VLP + GSK’s pandemic adjuvant||Medicago Inc. + Laval University||Phase 2 Clinical Trial – Canada||2 IM doses, 3 weeks apart;||N/A||21,27
LNP = lipid nanoparticles; mRNA = messenger ribonucleic acid; IM = intramuscular; VVnr = viral vector (Non-replicating); ChAd = chimpanzee adenovirus; S protein = spike protein; SARS-CoV2 = severe acute respiratory syndrome coronavirus 2; Ad26 = human serotype 26 adenovirus; PS = protein subunit; DNA = deoxyribonucleic acid;
Id = intradermal; LAV = live attenuated virus; IN = intranasal; VLP = virus-like particle
*Based on Phase 3 Clinical Trial data
** For emergency use
COVID-19 vaccine development continues to be an R&D priority to meet colossal demands for alleviating or even eradicating COVID-19. Unlike the recurring favourable outcomes achieved with COVID-19 vaccines, SARS and MERS vaccine developments were stalled in early clinical trial phases due to eradication and adverse reactions, respectively.9 In countries where vaccines have been approved, the elderly and frontline workers are prioritised. Additionally, the approved Pfizer-BioNTech vaccine has been shown to be effective, though to a lesser extent, against the COVID-19 variant which emerged in South-East United Kingdom.30 Nevertheless, Oxford’s vaccine was found to have only a 10% efficacy against the variant strain which was first isolated in South Africa, which led to a discontinuation of the vaccine’s rollout there.31 The onset of such mutants has caused vaccine developers to consider updating or producing second generation COVID-19 vaccines that would be more effective against variant strains.32
Since no vaccine is 100% effective, there are still some inconsistencies found with vaccination. For example, it is argued that a small percentage of people are not protected after vaccination – that they may still test positive since vaccines do not provide full or immediate protection, and do not work retroactively. Moreover, there is much talk of the fact that though the vaccines may prevent disease, experts are still uncertain of the chances of infection post-vaccination without manifestation of symptoms, and that the COVID-19 vaccines can merely just lead to acquiring a less severe or asymptomatic form of COVID-19 that can still spread. It is for reasons like these that vaccinated individuals are still required to wear masks.33 On another note, some people are unable to be vaccinated due to some immunosuppressive and/or hyperallergic conditions, whereas others refuse to be vaccinated for personal reasons. It is here that herd immunity would come into play, protecting such individuals indirectly from COVID-19 in a population that is immune either through vaccination or previous infection.18, 34 At least 70% of the population would have to achieve immunity for this to occur, and as much as 80-85% with the variant strains.35
Though this topic is highly controversial, vaccination is still considered the best remedy to combat COVID-19. Currently, much effort is being put into the global distribution of approved vaccines, as various countries across the globe, including Caribbean countries strike deals with vaccine developers and COVAX.36 About 171.4 million COVID-19 vaccine doses have been administered globally, with a rate of 6 million new vaccines being given on a daily basis.37
Ethical Approval Statement: Not applicable
Conflict of Interest Statement: There are no conflicts of interest to declare.
Informed Consent Statement: Not Applicable
Funding: Not applicable
Author Contribution: I am the sole author of this paper.
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- Caribbean Public Health Agency. CARPHA Situation Report NO. 128: COVID-19 Pandemic, 2021. https://carpha.org/Portals/0/Documents/COVID%20Situation%20Reports/Situation%20Report%20128%20-%20February%201,%202021.pdf (Accessed 02/02/2021).
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- World Health Organization. The COVID-19 candidate vaccine landscape 2021. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (Accessed February 14, 2021).
- National Institute for Health Research. First Children’s COVID-19 vaccine trial open 2021. https://www.nihr.ac.uk/news/first-childrens-covid-19-vaccine-trial-open/26870 (Accessed February 19,2021).
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