Dinkum Journal of Medical Innovations (DSMI)

Publication History

Submitted: July 03, 2023
Accepted: July 20, 2023
Published: August 01, 2023

Identification

D-0132

Citation

Marie Diack, Derak Stewart & Parshu Kirby (2023). Prospects and Challenges of Covid-19 Vaccination Development. Dinkum Journal of Medical Innovations, 2(08):302-312.

Copyright

© 2023 DJMI. All rights reserved

Prospects and Challenges of Covid-19 Vaccination DevelopmentReview Article

Marie Diack 1*, Derak Stewart 2, Parshu Kirby 3

  1. Nepal Medical College and Teaching Hospital (NMC), Nepal: diackmarie3@gmail.com
  2. Nepal Medical College and Teaching Hospital (NMC), Nepal: steward001@gmail.com
  3. Nepal Medical College and Teaching Hospital (NMC), Nepal: parshukirby88@outlook.com

*             Correspondence: diackmarie3@gmail.com

Abstract: The new coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2) was the cause of the coronavirus illness 2019 (COVID-19), which the WHO classified as a pandemic in March 2020. The first case of SARS-CoV-2 was discovered in Wuhan, China, in November 2019, marking the virus’s global debut. The prolonged creation of novel virus variations caused havoc in practically every field of life due to mutations in the SARS-CoV-2 genome. Authorised SARS-CoV-2 vaccines, such as DNA, mRNA, subunit, inactivated, and viral vector vaccines, as well as live attenuated and mix-and-match vaccines, will be covered in this article along with their mechanism, administration, stability, safety, and effectiveness. Through computerised searching on sites like PubMed, Science Direct, Google Scholar, and the WHO platform, information was gathered from a variety of journals. An overview of the pathophysiology, epidemiology, mutant variations, and management approaches associated with COVID-19 is provided in this review paper. Owing to the ongoing emergence of new SARS-CoV-2 strains and our inadequate comprehension of them, it is critical to close the gaps in our knowledge by combining theoretical and practical expertise to develop a vaccine that would provide both long-lasting protections against these strains. Therefore, it is essential to keep the literature up to speed with past and present vaccination experiments conducted across a range of age and ethnic groups in order to better understand management approaches and prevent issues related to upcoming novel SARS-CoV-2 variants.

Keywords: covid-19, vaccination, prospects, challenges, development

  1. INTRODUCTION

Previously known as novel coronavirus (2019-nCoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current global pandemic, also known as coronavirus disease (COVID-19). SARS-CoV-2 is a nucleocapsid phosphoprotein-encased ribonucleic acid (RNA) virus that can be detected in both people and wildlife. One of the biggest RNA viruses (26–32 kb) is coronavirus [1]. There are 14 open reading frames (ORFs) in the SARS-CoV genome, and these encode 27 structural and non-structural proteins. The membrane (M), spike (S), and nucleocapsid (N) proteins are the main structural proteins of coronaviruses [2]. Seven species, including the betacoronaviruses HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2, and the alphacoronaviruses HCoV-229E and HCoV-NL63, have been found to be somewhat harmful to humans [3]. The neurological, pulmonary, gastrointestinal, and hepatic systems have all been known to become infected by them [1-4]. In the last few decades, China (2002) and the Middle East (2012) have had endemic coronavirus outbreaks. The extremely contagious SARS-CoV-2 virus is the cause of yet another outbreak that has been observed [5]. The most recent outbreak began in Wuhan, China, with a group of individuals presenting with pneumonia of uncertain aetiology [6]. The recurrent emergence of coronavirus suggests that new coronaviruses will eventually evolve and that the virus can spread from animal to human and human to animal. Wuhan, China has been the epicentre of coronavirus activity since December 12, 2019 [7, 8]. It was initially described as an acute respiratory disease that no one had ever heard of. According to certain research, bats are most likely the source of the SARS-CoV-2 virus. On the other hand, there is no proof that the SARS-CoV-2 virus started at a seafood market. This theory is still unverified. A natural reservoir for a diverse range of coronaviruses, including viruses like MERS-Co-V and SARS-Co-V, is found in bats to a lesser degree [9–11]. It was predicted that the main ways in which SARS-CoV-2 would spread were by ingestion or direct contact with wild animals through intermediate host species. However, neither the SARS-CoV-2 source nor its mode of transmission have been determined with certainty. For around 11 months following the COVID-19 outbreak in late 2019, the virus’s genetic makeup remained steady. Then, in late 2020, clusters of SARS-CoV-2 mutations known as “variants of concern” (VOC) began to emerge. These changes had an impact on the virus’s transmissibility and antigenicity. This has led to the establishment of COVID-19. It most likely appeared as a result of the immunological profile of the human population changing. Moreover, a thorough discussion of SARS-CoV-2 mutant variations has been conducted by Harvey and colleagues [12], with a focus on the primary antigen, the spike protein. According to reports, the majority of mutations discovered in the genomes of SARS-CoV-2 virions in circulation are probably neutral or perhaps slightly harmful. This is due to the fact that “neutral” amino acid mutations, which don’t seem to affect the virus’s effectiveness or adaptability, are far more frequent than the uncommon “high-effect” mutations required for adaptation. For example, in April 2020, it was demonstrated that the spike protein amino acid mutation D614G was occurring more frequently and several times in the global SARS-CoV-2 population [13, 14]. Furthermore, a positive selection at codon position 614 is suggested by the high dN/dS ratio in the coding region [13, 14]. Subsequent research demonstrated that D614G had increased infectivity [15, 16] and transmission [17], which further corroborated this. The SARS-CoV-2 variant Omicron (B.1.1.529) was found in Botswana, South Africa, and Hong Kong in November 2021. Since then, it has been a source of concern as a VOC. As per the SARS-CoV-2 genome data provided on GISAID (https://www.gisaid.org), viewed on October 18, 2022, Omicron has been found in at least 85 countries, raising concerns about its potential high transmissibility. The most concerning aspect of Omicron is the abundance of mutations in the S protein, some of which are unique and others of which are shared with previous VOCs. Preliminary research indicates that Omicron has a remarkable potential to evade humoral immune responses, as evidenced by the quick drop in the neutralising power of antibodies and sera generated by infection and vaccination against Omicron [18–22]. However, Omicron’s ability to evade cellular immunological responses—the other part of the T cell-mediated adaptive immune system—remains uncertain. Primarily, enhanced comprehension of the phenotypic consequences of mutations throughout the SARS-CoV-2 genome and their consequences for variant survival could facilitate the deciphering of the mechanisms behind virus transmission and evolutionary triumph. The spectrum of clinical manifestations linked to COVID-19 is wide, ranging from people with no symptoms to those with multiple organ dysfunction. Based on the degree of infection, COVID-19 can be divided into four categories: mild, moderate, severe, and critical. Patients with COVID-19 infection may classify their typical symptoms into major and minor symptoms. Fever (98.6%), exhaustion (69.6%), dry cough, and body aches are the main symptoms, while dyspnea, gastrointestinal issues, headaches, and skin lesions are the minor symptoms [23]. Patients infected with SARS-CoV-2 have occasionally been observed to experience skin eruptions similar to vasculitis in conjunction with COVD-19 [24]. Overall, it was discovered that the range of symptoms changed consistently with regard to various variations. For example, compared to earlier versions, the highly contagious Omicron variant of SARS-CoV-2 caused less severe disease and had decreased replication in lung parenchyma. When comparing individuals infected with the Omicron variant to those infected with prior versions, such as Alpha, Beta, and Delta, a noteworthy decrease in self-reported chemosensory impairment, such as taste and smell, was noted in a research by Boscolo-Rizzo and colleagues [25]. In older children, SARS-CoV-2-associated multiorgan inflammatory syndrome has been linked to shock, cardiac failure, and stomach pain that resembles Kawasaki illness [26]. Individuals with SARS-CoV-2 infection may exhibit little to no signs of acute respiratory distress syndrome (ARDS), which can lead to multiple organ failure. Furthermore, the intensity of symptoms varies according to the patient’s age and is most likely linked to a weakened immune system. The most prevalent comorbidities associated with elderly SARS-CoV-2-infected patients include cardiovascular disease, diabetes, neurological disorders, and hypertension [25]. Being a member of the cytopathic virus family, SARS-CoV-2 targets cells in the host tissues during replication, causing harm to those tissues [27]. It is believed that Angiotensin-Converting Enzyme 2 (ACE2) is the main receptor that allows SARS-CoV-2 to enter host cells. It is essential for the gaseous exchange in the lungs for alveolar epithelial cells (Type II) to have ACE2 receptors on their surface. In addition, ACE2 is expressed on type I pneumocytes, endothelial cells, and tissues outside of the lung, including the kidney, heart, blood vessels, gut, and bladder [28, 29]. Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β), Tumour Necrosis Factor Alpha (TNF-α), Interferon-inducible protein 10 (IP10), Monocyte Chemoattractant Protein-1 (MCP-1), and regulated upon activation, normal T cell expressed and secreted (RANTES) similar to MERS virus have been found to be higher in SARS-CoV-2-infected patients. The release of chemokines and cytokines primes macrophages and monocytes, which in turn produces cytokines that prime the T cell adaptive immunological response [30]. In most cases, the virus will be invaded by activated macrophages and monocytes, which reduces inflammation. Whereby, in certain instances, patients with prior underlying medical disorders or immune systems that are impaired have shown signs of an unfavourable inflammatory response accompanied by a cytokine storm. Elevated levels of plasma cytokines, such as interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-10 (IL-10), granulocyte colony-stimulating factor (GCSF), IP-10, MCP-1, MIP-1α, and TNF-α, are typically used to classify this storm of cytokines [29,30,31, 32]. Such unchecked pulmonary inflammation is probably fatal. Furthermore, severe SARS-CoV-2 infections have also been connected to thrombosis and pulmonary embolism. In this instance, the liver’s increased synthesis of a clotting factor as a result of inflammatory cytokines has likely led to hyperactivation of platelets, which aggregates platelets at thrombin inappropriate quantities [33]. According to reports, receiving angiotensin receptor blockers (ARB) raises the chance of contracting SARS-CoV-2, especially in close-knit populations [34]. However, in a different retrospective analysis, there was no significant correlation seen between the use of ARBs and COVID-19 diagnostic elevation, severity, or death [35]. However, the immune response’s mechanism and the molecular pathways linked to SARS-CoV-2 remain hazy and unclear. To create a treatment drug that works, it is critical to understand these pathways, particularly for the anticipated novel SARS-CoV-2 variants. During the early stages of the SARS-CoV-2 epidemic, isolation was still the most effective method for keeping the virus under control [36]. Quarantine, sanitizer use, and social separation were some of the tactics employed to fight SARS-CoV-2 outbreaks. There was no particular medication or vaccination available to treat the viral illness in the early stages of the coronavirus pandemic. Before the World Health Organisation approved the SARS-CoV-2 vaccine, patients with mild infections basically needed to be treated with supportive care, which included paracetamol, chilling the affected area with an external device, and nutritional supplements for oxygen therapy. Conversely, patients in critical condition needed convalescent plasma, glucocorticoid medication, and high-flow oxygen [1,37]. As of right now, a number of vaccinations and antiviral medications have received approval to treat SARS-CoV-2 infections and lessen their severity [37]. The FDA has approved tixagevimab and cilgavimab, two monoclonal antibodies (mAbs), for the pre-exposure prophylaxis of COVID-19 in people who have severe allergies to the SARS-CoV-2 vaccine. The injection of these monoclonal antibodies can be done intravenously (IV) or intramuscularly (IM). Viral entrance into the host was inhibited by ixagevimab and cilgavimab, suggesting possible efficacy against the Delta version of SARS-CoV-2 [38]. Since respiratory failure and systemic inflammation in COVID-19 patients may be linked to increased cytokine release, the FDA has approved anti-IL6 medications for these patients. IL-6 is a pro-inflammatory cytokine. After testing in patients with systemic inflammation, the FDA approved two kinds of IL-6 inhibitors: anti-IL-6 receptor mAbs (like tocilizumab and sarilumab) and anti-IL-6 mAbs (like siltuximab) [39]. In addition, there are oral antivirals that can be used to treat COVID-19, such as molnupiravir and nirmatrelvir plus ritonavir. In a real-life retrospective analysis, these antivirals showed a significant reduction in hospitalisation, mortality, and illness severity, especially among vaccinated persons with severe comorbidities [40]. Dexamethasone, a corticosteroid family member, has been successfully used to lower mortality in COVID-19 patients exhibiting an intense respiratory response [41]. Remdesivir, a nucleotide inhibitor that has FDA approval, has also been shown to lessen the severity of SARS-CoV-2 infection and has a low mortality or hospitalisation risk [42]. Based on the usage of remdesivir and sotrovimab in an outpatient setting, to lower the risk of hospitalisation, Piccicacco and colleagues observed a similar result [43].

  1. LITERATURE REVIEW

The vaccine, which was developed using the messenger RNA (mRNA) platform, was very effective in managing SARS-CoV-2 infections, especially those caused by the Alpha, Beta, and Delta variants. It also specifically assisted in lowering the severity of illnesses. It shown that it could be taken into consideration as a more concentrated platform for upcoming vaccine development. It shown its enormous potential to considerably slow the spread of vaccines that target numerous infections. The current success of mRNA vaccines can be attributed to their quick manufacturing, ability to demonstrate the Th1 and Th2 responses, mRNA alterations, stabilisation, and administration strategies [44]. Compared to DNA, RNA molecules are easier to transcribe in vitro and are smaller. Lipid nanoparticles have been used to protect the prefusion-stabilized S protein-encoding mRNA in mRNA vaccine delivery. Moreover, a variety of other materials have been included in the vaccine development process [45]. Among the effective mRNA vaccines that have been used in clinical trials with more than 90% efficacy against SARS-CoV-2 are Pfizer/BioNTech BNT162b2 and Moderna mRNA-1273. Very few side effects have been reported, primarily local and systemic reactogenicity [46]. Pfizer/BioNTech BNT162b2 and Moderna mRNA-1273 vaccines, each containing 30 µg, are typically given in two doses with a maximum interval of 21 and 28 days, respectively. The Moderna mRNA-1273 vaccine and the Pfizer/BioNTech BNT162b2 vaccine have enhanced stability through a decrease in the unwanted type I interferon immune response. A number of trials have been planned to evaluate the effectiveness of mRNA vaccines against novel strains of SARS-CoV-2 in children. The vaccines Moderna mRNA-1273 and Pfizer/BioNTech BNT162b2 should be stored at −25 to −15 °C and −80 to −60 °C, respectively; at room temperature for ≤12 and ≤2 hours and 2–8 °C for 30 days and 5 days, respectively. In addition, several studies are undergoing clinical trials to evaluate the effectiveness of mRNA vaccines against severe viral infections such as rabies, influenza, ZIKA, and HIV [47]. It is concluded that future research and vaccine development will heavily focus on mRNA vaccines. SARS-CoV-2 subunit vaccines are made of recombinant proteins that are unique viral antigenic particles with high immunogenicity. Because there is no risk of handling live virus particles or genome integration during the production process, subunit vaccinations are comparatively safer. Consequently, subunit vaccinations are typically regarded as safe and well-tolerated vaccinations. This kind of vaccination approach frequently requires efficient adjuvants in addition to safety and tolerance in order to produce a higher immune response. In comparison to vaccines containing inactivated microorganisms, they are relatively safer. The S protein or the S protein’s receptor-binding domain (RBD) are used as antigens in these vaccinations [48]. The SCB-2019 vaccine from Clover Biopharmaceuticals AUS Pty Ltd., Chengdu, Sichuan, China; NVX-CoV2373 from Novavax; Covax-19 from GeneCure Biotechnologies; Adelaide, Australia’s Vaxine Pty Ltd.; and MVC-COV1901 from Medigen Vaccine Biologics Corp. are a few instances of subunit vaccines that remove the S protein as an antigen. On the other hand, two subunit vaccines, KBP-COVID-19 from Kentucky BioProcessing, Inc. and the vaccine from Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd., Anhui, China, use the RDB domain of the S protein as an antigen. With an efficacy rate of 89.5%, the subunit vaccine NVX-CoV2373 by Novavax, which uses the saponin-based Matrix-M adjuvant, is presently undergoing a phase 3 trial and has been given approval by the FDA and WHO to be used in the pandemic. The Novavax vaccine, which has a months-long shelf life at 2–8°C, is typically given in two doses consisting of 5 µg of protein and 50 µg of Matrix-M adjuvant [49]. Conversely, phase 1 and 2 clinical studies are presently being conducted for additional subunit vaccines. Currently undergoing preclinical evaluation are 55 protein subunit vaccines. In a clinical trial, NVX-CoV2373 was given to 83 participants with adjuvants and 25 participants without adjuvants. The findings showed minimal to no local and systemic reactogenicity, along with extremely modest side effects such fatigue, headaches, and malaise. Trials using adjuvants for subunit vaccinations showed increased immune responses and a Th1 cell-induced product. Furthermore, two doses of the adjuvant-based subunit vaccination produced anti-spike immunoglobulin G (IgG) with a neutralising response. It should be noted that anti-spike IgG levels were 100 times higher in those exhibiting COVID-19 symptoms [50]. The generation of antigenic isotopes from inactivated SARS-CoV-2 is the basis of the second most successful vaccination platform. Using this method, stable antigen epitope conformers have been obtained by chemically cultivating and inactivating virus particles. Because inactivated vaccines contain a variety of antigenic components, they can elicit a wide range of immune responses [51]. There are two doses of these vaccinations administered. Sinopharm and Sinovac are two such vaccinations. The WHO has approved the emergency use of these vaccinations for COVID-19 patients in China, Brazil, Columbia, Chile, UAE, Peru, Turkey, and Indonesia. For Sinovac Biotech, two dosages are given at intervals of 14 days; for Sinopharm, the intervals are 21 days, with an approximate 80% efficacy. At 2–8 °C, these vaccinations are kept in storage [52]. Numerous viral structural proteins are involved in these vaccinations, which aid in mimicking the structure of viruses. These vaccines are incredibly protected and totally non-infectious because they don’t contain any viral DNA. Recombinant virus-like particles are created by combining primary proteins from different viruses (VLPs). Since plant cells are in a prime state for the creation of oral vaccinations, these immunisations are frequently made in plants. Most people refer to these vaccinations as edible vaccines. Pathogenic Agrobacterium is used to associate genes for viral proteins with plants as a host. The desired gene is integrated into the chloroplast genome as a result of an infection that follows [53]. As a result, this alteration induces a significant amount of virus-like particle biosynthesis in plants. The previous vaccination against the influenza a virus (A/H1N1, A/H3N2) and avian influenza H5 (AIV) was durable and well-protected. Furthermore, these vaccinations showed promise against Lyme and Newcastle illnesses. Moreover, cross-reactive humoral and cellular responses were confirmed to be strong points for VLPs vaccinations. There are fifteen vaccines for SARS-CoV-2 undergoing pre-clinical studies. Among these, plant-derived VLP (Medicago) and (RBD SARS-CoV-2) HBsAg VLP were only included in clinical phase 1 trials. Compared to prior SARS-CoV-2 vaccinations, the VLPs vaccine exhibits greater stability at a higher temperature, specifically 25°C, for a two-week period [54]. Several factors need to be taken into account while discussing the difficulties surrounding the SARS-CoV-2 vaccination. Vaccination is considered the most effective means of preventing numerous infectious diseases, when compared to alternative choices. Vaccines function by stimulating the body’s immune system at the same time that an infection normally arises [55]. For a vaccination to be effective against infections, a foreign substance must function as a vaccine-active agent and stimulate immunological memory [56]. In addition to the creation of novel variations, there is a lack and resistance to COVID-19 vaccinations, particularly in underdeveloped areas. Due to the aforementioned difficulties, a considerable rise in IgG and neutralising antibodies with a robust cellular immune response resulted from the mixing of SARS-CoV-2 vaccinations in numerous countries [57]. Furthermore, compared to homologous vaccines, heterologous SARS-CoV-2 vaccinations have produced larger amounts of neutralising antibodies. As a result, combining SARS-CoV-2 vaccinations is widely used in both industrialised and underdeveloped nations. The goal of this novel approach was to immunise a significant portion of the population against SARS-CoV-2 with greater efficacy and fewer negative side effects [58]. This will benefit the areas impacted by a scarcity of more effective SARS-CoV-2 vaccinations against diseases associated with the virus. Since 2019, there have been several SARS-CoV-2 variations reported worldwide. Increased viral transmission is more likely, particularly when infections are still quite severe [97]. It is important to note that an increase in mutations directly correlates with a higher infection rate, hence aiding in the virus’s survival and growth [58]. The two main factors that directly affect the evolution of viruses are crowd resistance and herd immunity [59]. Some factors, such a lack of tolerance to novel pathogens, make these genetic alterations linked to viruses vital in the human genome. Replication processes are also accelerated by the SARS-CoV-2 transformation rates, which encode a protein with editing capabilities [60]. A study that looked at the SARS-CoV-2 gene sequencing was carried out to investigate potential alterations in the virus. The results revealed that 203,346 human genomes of SARS-CoV-2 had 26,844 single transformations that were sustained. During the three-year period between 2020 and 2022, the most well-known alterations were to S proteins and non-structural protein 3 (NSP3) [61]. By the end of December 2020, the S protein had undergone almost 5000 changes. Novel strains have surfaced globally, with the United Kingdom being the primary source. Examples include lineage B.1.1.7 and variant 20I/501Y.V1. Many mutations in the spike (S) protein, such as deletion 145, N501Y, deletion 69–70, D614G, A570D, T716I, P681H, D1118H, and S982A, are the cause of these variants. This mutation has been found in about 82 countries and has been linked to increased rates of transmission, severe illness, and decreased neutralisation efficiency [62]. Additionally, a different variant (variant 20H/501Y.V2) with eight mutations via the S protein was found in lineage B.1.351 in South Africa. These mutations are D80A, L18F, R246I, D215G, E484K, K417N, A701V, and N501Y. This variation was reported in 35 countries and was linked to increased transmissions and reinfections [63]. Lineage 20 J/501Y.V3 and lineage P.1, modified through three S protein mutations, N501Y, E484K, and K417N, are shared by the variation reported from Brazil and 20J/501Y.V2 [64]. With identical risk factors to the Brazil version, the variant was identified in 14 other countries. The N501Y mutation pertaining to the SARS-CoV-2 spike (S) protein, which is thought to be the primary target of the majority of vaccines, is a crucial component shared by all of these variants [65]. In November 2021, Omicron, a further variation, was found in South Africa. This variant is associated with the B 1.1.529 lineage and the following mutations: H655Y, N679K, P681H, R203K, G204R, E484, D614G, R93K, and G204R. Higher rates of reinfection and transmission were observed in 87 countries [65]. With B 1.1.1617 lineage, the first incidence of the new variant known as Delta was documented in India in October 2020. The Delta variation showed increased susceptibility to infection and spread. Following the Delta variation, Omicron and its subvariants are responsible for a fresh wave of SARS-CoV-2 virus. When compared to other variants, Omicron is said to have the most mutations. While Omicron and its subvariants exhibited comparatively lower infection severity than other variations, the rate of transmission is raised and has been reported to be nearly 3.8 times higher than that of the Delta variant [66]. The Omicron variant’s capacity to evade the immune system and so lessen the effectiveness of vaccinations is its most worrisome discovery. Of the Omicron variety, more than 50 mutations have been identified to date, 32 of which are found in the SARS-CoV-2 spike protein [67]. Future significant and in-depth study is necessary because there is a dearth of information on the effects of current SARS-CoV-2 vaccinations, particularly with regard to the transmission and neutralisation of new variations.

  1. CONCLUSION

SARS-CoV-2 is the causal agent of the present pandemic and continues to cause higher-order mortalities. Healthcare services worldwide continue to face a significant socioeconomic burden despite the introduction of numerous treatments to manage viral infection. Even after three consecutive waves of the epidemic, the precise makeup and transformational potential of the SARS-CoV-2 virus remain clear. Nevertheless, there are conflicting accounts regarding the recent outbreak. The spike glycoprotein-targeting first-generation SARS-CoV-2 vaccinations have demonstrated promise in limiting the virus’s spread. Regrettably, locally circulating disease variations have impaired the efficacy of the currently available immunisations. Thus, an extended investigation of neutralising activity is necessary in order to evaluate the resilience of protective antibodies against novel mutations.

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Publication History

Submitted: July 03, 2023
Accepted: July 20, 2023
Published: August 01, 2023

Identification

D-0132

Citation

Marie Diack, Derak Stewart & Parshu Kirby (2023). Prospects and Challenges of Covid-19 Vaccination Development. Dinkum Journal of Medical Innovations, 2(08):302-312.

Copyright

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