|Year : 2021 | Volume
| Issue : 2 | Page : 92-98
COVID-19 vaccine in the Kingdom of Saudi Arabia: A true operation warp speed
Mazin Barry1, Ahmed S BaHammam2
1 Department of Internal Medicine, Division of Infectious Diseases, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Department of Medicine, University Sleep Disorders Center and Pulmonary Service, King Saud University, Riyadh; The Strategic Technologies Program of the National Plan for Sciences and Technology and Innovation in the Kingdom of Saudi Arabia (08-MED511-02), Saudi Arabia
|Date of Submission||15-Jan-2021|
|Date of Decision||31-Jan-2021|
|Date of Acceptance||01-Feb-2021|
|Date of Web Publication||25-Feb-2021|
College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461
Source of Support: None, Conflict of Interest: None
As of January 2021, 1 year has passed since the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first discovered, which is the cause of the coronavirus disease-2019 (COVID-19) pandemic that has infected almost 100 million people worldwide and caused almost two million deaths. In 2020, in an unprecedented scientific achievement, several vaccines were developed, underwent clinical trials, and were distributed worldwide. This was made possible, in part, by Operation Warp Speed, which promoted mass production of multiple vaccines through different technological platforms, relying on preliminary evidence to allow faster distribution as soon as clinical trials confirmed one or more of those vaccines to be safe and effective. The Kingdom of Saudi Arabia (KSA) was one of the very first countries in the world to grant emergency use authorization to the BNT162b2 vaccine, a new type of modified RNA vaccine developed by Pfizer-BioNTech. Here, we review various COVID-19 vaccines and the success of the vaccine rollout in KSA.
Keywords: BNT162b2, Pfizer-BioNTech, RNA vaccine, severe acute respiratory syndrome coronavirus-2
|How to cite this article:|
Barry M, BaHammam AS. COVID-19 vaccine in the Kingdom of Saudi Arabia: A true operation warp speed. J Nat Sci Med 2021;4:92-8
| Introduction|| |
Ever since the initial outbreak in December 2019 of what would come to be known as coronavirus disease-2019 (COVID-19), it was clear that vaccines were urgently needed. The scientific community and academicians, as well as industry leaders, made vaccines a priority. When the full genetic sequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was released and made available to scientists on January 11, 2020, only 10 days after the virus was isolated, vaccine research and development (R&D) was immediately started with several vaccine types and candidates. An anti-spike protein was created within 2 days. Now, at least 200 vaccine candidates have been developed, of which almost 80 are confirmed to be active in vitro. They include RNA- and DNA-based vaccines, virus-like particles, peptides, viral vectors, recombinant proteins, live attenuated viruses, and inactivated viruses. [Table 1] demonstrates the major vaccines that have been rolled out in different countries.
|Table 1: Major vaccines that have been authorized and rolled out in different countries|
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| RNA Vaccines|| |
Of the greatest potential for rapid scale-up are RNA-based vaccine platforms, which can be quickly developed because they use completely synthetic processes and do not need cell culture or fermentation like conventional vaccines. In addition, their use of genetic sequencing speeds up development time and has the advantage of being able to manipulate targeted antigens., They also have the capacity for rapid development, low-cost manufacturing, and safe administration.
The most prominent developed RNA vaccine is the Pfizer-BioNTech COVID-19 vaccine, BNT162b2, which is a lipid nanoparticle (LNP) that encapsulates nucleoside-modified mRNA that encodes the SARS-CoV-2 full-length spike (S) protein. Phase I and II trials confirmed its immunogenicity with high cellular and humoral responses, paving the way for its triumphant Phase III randomized clinical trial that was started in July 2020. Almost 44,000 participants were enrolled and the results showed an efficacy of 95%. This vaccine received emergency use authorization by the Medicines and Healthcare products Regulatory Agency (MHRA) of the U. K. on December 2, 2020, by the Kingdom of Saudi Arabia's (KSA) Saudi Food and Drug Authority (SFDA) on December 10, 2020, by the U. S. Food and Drug Administration on December 11, 2020, and by the E. U.'s European Medicines Agency (EMA) on December 21, 2020.
This particular vaccine's major challenge is that it needs ultra-low-temperature storage (−80°C to −60°C) and can only be kept at room temperature for a maximum of two hours. Moreover, it is not interchangeable with other vaccines. Its only contraindication is a known history of severe allergic reactions, especially anaphylaxis, to any vaccine component, including polyethylene glycol and polysorbate. It is currently not indicated in pregnant or lactating women or children under 16 years of age due to a lack of safety and efficacy data. Its adverse effects are minor and mostly local, including injection-site pain and swelling. Lymphadenopathy has been reported. Systemic symptoms such as fever, chills, myalgia, and headache are rare.
With its impressive efficacy and safety, many questions remain as data beyond 2 months are still unknown, and its safety in children, pregnant women, patients with autoimmune diseases, and immunocompromised individuals is also unknown. In addition, it is still not clear whether the vaccine protects against asymptomatic infection and transmission to unvaccinated persons, and what should be done with patients who miss their second dose.
The second RNA vaccine, mRNA-1273, was developed by Moderna and is also an LNP-encapsulated mRNA vaccine. It showed an efficacy of 94% in its Phase III clinical trial. It is currently authorized in the U. S. and Canada through an emergency use authorization that was granted on December 18, 2020, and December 23, 2020, respectively, and is indicated in individuals aged 18 years or older. Similarly, it must be frozen but at higher temperatures (−25°C to −15°C) compared to the Pfizer-BioNTech BNT162b2 COVID-19 vaccine and has the advantage that it can be refrigerated at 2°C to 8°C for up to 30 days. It is also not interchangeable with other vaccines, and its only contraindication is any known history of severe allergic reactions to any component of the vaccine. Data on immunocompromised patients suggest they may have a diminished response. It is not to be administered to pregnant or lactating women, nor children. Its main adverse effects are similar to BNT162b2, the most common of which is injection site pain.
A more recent LNP-encapsulated mRNA vaccine from Osaka University in Japan, ARCoV, targets the receptor-binding domain of SARS-CoV-2. It is currently in Phase II and III trials. It has been shown to be immunogenic and has the great advantage of being thermostable.
A German biopharmaceutical company, CureVac, developed CVnCoV, an LNP-encapsulated mRNA vaccine that encodes for the full-length spike protein. This vaccine requires 5°C for storage and can be maintained at room temperature for 24 h. A Phase I trial on 245 participants showed a good safety profile with dose-dependent adverse effects and high seroconversion rates. It is currently undergoing Phase IIb/III trials with 36,500 participants in Europe.
| Other Vaccines in the Pipeline|| |
Several viral vector vaccines have been developed, including the chimpanzee adenovirus-vectored ChAdOx1 nCov-19 by Oxford/AstraZeneca. Its Phase III trial had a difficult start as reports of transverse myelitis emerged on September 8, 2020, halting the trial for 7 days. In an interim analysis of almost 12,000 participants of its Phase III trial, participants who received two standard doses showed an efficacy of 62%; however, participants who received an initial substandard low dose followed by a second standard dose showed an efficacy of 90%. Despite these discrepancies, the overall efficacy was reported as 70% for both regimens used, and it also showed an overall acceptable safety profile. It was granted emergency use authorization by the MHRA in the U. K. on December 30, 2020.
The Ad5-nCoV vaccine, developed by CanSino Biological of Beijing Institute of Biotechnology, uses adenovirus type 5 as a viral vector. In a Phase II trial of 600 participants, it was found to be safe with significant immune responses. Adverse effects included pain at the injection site, which was experienced by more than half of the study participants. Fever was also reported and was most common in females and patients under 55 years of age.
Other vaccines in the pipeline include BBIBP-CorV, an inactivated virus vaccine developed by Sinopharm of the China National Pharmaceutical Group. It has the advantage of being developed by older technologies with well-established vaccine platforms. According to a recently published Phase II trial of almost 450 participants, all vaccine recipients developed antibodies and reported only mild adverse effects, such as pain and fever. Phase III trials have been ongoing. This vaccine has been rolled out in the Kingdom of Bahrain after the National Health Regulatory Authority approved its registration. The United Arab Emirates' Ministry of Health and Prevention (MOHAP) granted emergency use authorization and rolled it out to its citizens, in addition to conducting a Phase III trial on 31,000 volunteers.
CoronaVac, also an inactivated SARS-CoV-2 vaccine, was developed by Sinovac Biotech. It is currently undergoing multinational Phase III clinical trials. Interim analysis from several sites reported discrepancies in their efficacy results. In Turkey, the efficacy was announced to be 90% based on 30 cases out of only 1300 participants in a clinical trial with over 7300 volunteers who were not included in the analysis. In Indonesia, efficacy was announced to be 65% based on data from only 1600 participants. On January 12, 2021, Brazil announced an efficacy of only 50% based on data from almost 12,500 participants.
The very first vaccine, Gam-COVID-Vac (trade-named Sputnik V), was developed by Gamaleya Research Institute of Epidemiology and Microbiology in Russia. It is a viral vector vaccine based on two adenovirus serotypes (Ad26 and Ad5); in a Phase I-II trial, all 76 participants developed antibodies. Adverse effects included minor local reactions. Phase III results are ongoing, and a second interim analysis released by the company reported 91% efficacy in a trial performed on almost 19,000 participants.
Ad26.COV2.S, developed by Johnson and Johnson, uses an adenovirus serotype Ad26 vector and encodes a full-length SARS-CoV-2 spike protein. Per an interim analysis of a Phase I-II trial in which a total of 805 participants were enrolled, adverse effects were common, mostly injection-site pain. The efficacy was between 96% and 99%.
Other technologies include NVX-CoV2373, a SARS-CoV-2 recombinant spike protein nanoparticle with matrix adjuvant, developed by Novavax. A Phase I-II trial, which included 83 participants, showed a good safety profile and strong immune response. The Phase III trial, PREVENT-19, started enrolling 30,000 participants in December 2020.
| Coronavirus Disease 2019 Vaccine in the Kingdom of Saudi Arabia|| |
The first case of COVID-19 in the KSA was reported on March 2, 2020. Caseloads peaked during the month of June, and the highest number of new cases in a single day, 4919, was reported on June 18, 2020. As of January 13, 2021, KSA has reported 364,096 laboratory-confirmed cases with 6300 deaths. KSA implemented strong national mitigation measures to curb the pandemic, which included travel restrictions, mandatory universal masking, and lockdowns. Its leadership in combating the pandemic has been a role model worldwide because of its bold measures despite all challenges. As part of its ongoing efforts to curb the pandemic, KSA planned early on to provide its population with COVID-19 vaccination as soon as a safe and effective vaccine became available. The same day that the Phase III trial of Pfizer-BioNTech COVID-19 vaccine was published, the SFDA granted emergency use authorization to the vaccine. Six days later, on December 16, 2020, KSA received its first two shipments of BNT162b2 and the next day, it immediately started mass campaigns to vaccinate its citizens and residents free of charge. Earlier, the Ministry of Health (MOH) requested that the population register to receive the vaccine via online platforms and smartphone applications and provided a supportive digital infrastructure for doing so. Vaccines were distributed within major cities. To meet the freezing storage conditions of the vaccine, mass vaccination centers were erected with up to 550 inoculation stations in each. The country's top leaders were among the very first to receive the vaccine in publicly televised events, which strongly encouraged the public and helped build confidence in the vaccine. Patients who reported visiting the vaccination centers stated that it took them a mere 15 minutes from the moment they arrived and confirmed their registration to receive the vaccine and complete the postvaccination observation [Figure 1]. The high-flow and rapid turnaround of visitors highlights KSA's experience in organizing mass gathering events related to Hajj [Figure 2].
|Figure 1: A Saudi woman after receiving her first dose of coronavirus disease-2019 vaccine in Riyadh, on December 17, 2020|
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|Figure 2: Inoculation sites inside Riyadh's vaccination center in preparation to receive patients|
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As part of vaccine rollout, KSA planned a phased approach [Table 2] to initially target the most vulnerable populations, including first responders, health-care workers (HCWs), individuals with comorbid illnesses, and the elderly. A second and third phase will follow, with the goal of vaccinating at least 70% of the whole population. What remains a challenge is vaccine confidence and hesitancy. In a nation-wide survey of 3,100 participants, only 45% were willing to receive a COVID-19 vaccine, although another public survey with almost 1000 participants showed a higher acceptance rate of 65%. A recent national cross-sectional survey in KSA of nearly 2,000 HCWs, three-quarters were willing to receive a COVID-19 vaccine; however, a survey specifically inquiring about willingness to receive the BNT162b2 vaccine showed that only a fifth of HCWs were willing to do so.
|Table 2: Phased approach to coronavirus disease-2019 vaccine allocation in the Kingdom of Saudi Arabia|
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Since the beginning of the pandemic, misinformation, dubbed a “massive infodemic,” has led to the spread of many misconceptions [Table 3]. KSA considers spreading rumors and fake news on COVID-19 that may harm the public to be cybercrime. Misinformation was foreseen as a possible barrier against vaccine uptake; hence, the country's top leaders have acted as vaccine champions. KSA's minister of health received the vaccine on the very 1st day of the campaign; on December 25, 2020, His Royal Highness Prince Mohammed bin Salman bin Abdulaziz, Crown Prince, Deputy Prime Minister, and Minister of Defense, received the first dose of the vaccine. On January 8, 2021, the Custodian of the Two Holy Mosques, King Salman bin Abdulaziz Al Saud, received the first dose of the Pfizer-BioNTech COVID-19 vaccine. All the events were celebrated and broadcast on national television and multiple media platforms. The events boosted vaccine confidence among the public and subsequently led to a large surge in the number of people registering for vaccination.
|Table 3: Common misinformation and misconceptions on coronavirus disease-2019 vaccines and their scientific rebuttal|
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In addition, clinicians and public health officials arranged open discussions in the media to answer key questions and concerns from the public regarding the risks and benefits of vaccination and its role in preventing COVID-19. They highlighted its major importance while establishing transparency through direct dialogue. Focused education was targeted toward HCWs so that they could advocate and guide their vulnerable patients to receive the vaccine.
In December 2020, a new SARS-CoV-2 variant (VOC 202012/01) emerged in the U. K. and is estimated to be almost 50% more contagious. This variant within the B.1.1.7 lineage has several mutations; the most significant is N501Y within the S protein. The BNT162b2 vaccine was shown to neutralize the N501 and Y501 viruses in vitro. This supports the ongoing vaccination campaign with BNT162b2 and validates KSA's choice of the vaccine.
KSA's role in curbing the pandemic extends even further by encouraging and supporting R&D. Recently, researchers at Imam Abdulrahman Bin Faisal University and the Institute for Research and Medical Consultations developed a SARS-CoV-2 vaccine candidate by encoding the S protein that was generated using plasmid DNA technology. Animal models demonstrated potent neutralizing antibody responses to the two dosing regimens tested.
The world may finally be able to curb the COVID-19 pandemic through vaccine research, development, and distribution. With its long-term vision, decisive leadership, and successful vaccine rollout, the KSA is a role model in implementing a real Operation Warp Speed for other countries to follow.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]