SEMANTIC SCHOLAR REVIEW IN THE CLINICAL SUCCESS OF DIFFERENTLY ENGINEERED VACCINES TO NEUTRALIZE SARS-CoV-2

Review article

Vol.8 Issue Page.1  No 25-45

Rajendra Kumar, Gaurav Sharma and Sarmad Moin*

School of Applied Sciences, Suresh Gyan Vihar University, Jaipur, India

Keywords

COVID-19

SARS-CoV-2

Protein

Spike

Immune

Antibody

*Corresponding author’s e-mail addresses: moinsarmad@gmail.com

Paper Received – 14/10/2021   Paper Accepted: 11/02/2022

Abstract

COVID-19 pandemic from 2019 to present, dramatically affects the human lifestyle with strict challenges to pause the SARS corona virus transmission globally. The appearance of SARS-CoV-2 leads to the development of various efficient WHO-approved novel corona vaccines like Ad26.COV2.S/Janssen, Ad5-Ncov/CanSino, Sputnik V, AZD1222/Covishield, mRNA-1273/Moderna, BNT162b1-2/Pfizer-BioNTech, BBV152/Covaxin, NVX-CoV2373/Novavax, ZyCoV-D/Zydus candila, CoronaVac/Sinovac, etc. by countries based on mRNA, DNA, protein, and recombinant vector immunogens. Vaccines are routed in ID, IM with 0.5mL with two or three doses maximum apart 28 days has a different rate of efficacy. Immune response and vaccine neutralising rate are affected by the occurrence of a new mutant SARS-CoV-2 strain with a new antigen epitope.

Introduction

SARS has the global power of novel diseases in western communities (Lederberg et al., 2003). People with COVID-19 have reported a wide range of symptoms, ranging from mild Revised: JAN/11/2022 symptoms to severe illness. Symptoms may appear 2 to 14 days after exposure to the virus. Symptoms may include fever or chills; cough; shortness of breath; fatigue; muscle or body aches; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting; diarrhoea. Interspecies transmission of SARS-CoV-2 to human-to-human transmission and the nonstop international traveller exploded the local outbreak of an emerging novel disease into a hygienic pandemic. The most recent emerging zoonotic origin of novel diseases Nipah virus, Hendra virus, and SARS-CoV that have a wildlife reservoir cause threats to human health (Peiris et al., 2004). The disease “infectious atypical pneumonia” first emerged in Guangdong, 2002 due to contact with the live-game trade (Zhong et al., 2003; Xu et al., 2004). SARS was identified as a novel coronavirus (Peiris et al., 2003; Ksiazek et al., 2003; Drosten et al., 2003) with its propensity to cause clusters of disease in families and healthcare workers (Zhong et al., 2003; Peiris et al., 2004). The global scale of the disease SARS-CoV-2 resembles the human immunodeficiency virus. Tis SARS outbreak illustrates the potential health effects by the risk of the re-emergence of the disease that may derive from an animal reservoir or infections transmitted in the laboratory (Guan et al., 2003; http://www.moh.gov.sg/sars/pdf/ Report_SARS_Biosafety.pdf). SARS has the potential survival ability to skip off any of the uncertain seasonal duration in the host as the asymptomatic condition, brings attention for the continuation of detection and diagnosis. As active surveillance for severe respiratory disease inclusive of health care workers, the rapid diagnosis and prevention of other respiratory viruses must be preferential (Peiris et al., 2003). SARS is an acute lung alveolar disease that has a significant impact on morbidity and mortality in a cohort of zoonotic (Lee et al., 2003) within a period of fewer than two months, SARS has become a global health problem, prompting the WHO to issue a global alert for the first time in more than a decade (http://www.who.int/csr/ sarscountry/2003_03_27; Lee et al., 2003).

Corona virus

The finding of infectious coronavirus in the respiratory tract supports epidemiological data to suggest that the virus is spread by direct and indirect contact (Ksiazek et al., 2003). The SARS-CoV-2 was first reported in samples of Broncho-alveolar lavage fluid from three patients in Wuhan Jinyintan hospital and was confirmed as the cause of COVID-19 on January 24, 2020 (Huang et al., 2019). The similarity of clinical symptoms between corona virus-19 and beta-corona virus suggest that the incidence of severity and mortality of COVID-19 is beyond chronic diseases had an impression on age distribution, daily lifestyle, and dietary habits of the Human population (Hu et al., 2019). The different age group has a different rate of infection. Many of the biomarkers and responsive factors like as oxygenation index, bilateral lung plaque shadow, and biochemical indexes (decreased lymphocyte count, increased C-reactive protein, increased aspartate aminotransferase, increased lactate dehydrogenase and creatine kinase appear to refer to the presence of coronavirus in that human host (Zheng et al., 2020). Coronaviruses have a different variant of infectious viruses in humans and may transmit through animals to humans or human to human out of them Rats, Cats, Bats, and Camels are the main host (Du et al., 2009). Coronavirus found with different rate of mortality with respect of country to country, as reported by WHO dated 29 March 2020 (Advice for public [Internet]. Who.int. 2018 [cited 2020 Jun 3], Sajed et al., 2020).

SARS-CoV-2

The International Committee on Taxonomy of Viruses termed corona virus as SARS-CoV-2 while COVID-19 coined by the world health organization (WHO) that have an adverse effect of the severe acute respiratory syndrome (Mesev et al., 2019). SARS-CoV-2 genomic sequence is 70% identical to SARS-CoV and 50% with the Middle Eastern respiratory syndrome coronavirus (MERS-CoV) (Lu et al., 2020). COVID-19 virus is a ribonucleo-particle that contains a positive sense single-strand RNA sequence as a genetic material composed of protein capsules (Hoffmann et al., 2020). Protein capsule embedded the spike glycoprotein (S) majorly that’s the major immunogen particle in coronavirus to bind with human angiotensin-converting enzyme-2 (hACE2) to initiate infection.4 Spike glycoprotein has 2 subunits which are the main antibody targets (Roush et al., 2007; Verhees et al., 2018). 2019-nCoV prevalence is much more but the severity rate is higher of MERS and SARS. Clinical suggestion to minimize the COVID-19 is early screening, diagnosis, isolation, and treatment are necessary to prevent spread (Sajed et al., 2020). Taxonomy suggest that corona virus belongs to family Coronaviridae, order Nidovirales and classified into four genera, coronavirus-a, coronavirus-b, coronavirus-g, and lastly coronavirus-d that have many mutant strains (Li et al., 2016). Coronaviruses-b have a most privileged strain of COVID-19 are Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) (Bakkers et al., 2017). So SARS-CoV-2 is identified as that of b- coronavirus (Chen et al., 2020). The crown-shaped appearance of spike protein (S) is termed the name of COVID-19 as corona in Latin (corona- a crown) virus (Siddell et al., 1995; Coutard et al., 2020). Another study of microscopic imaging of SARS-CoV-2 presenting crown-like outgrowth indicates again belongs to a family of coronaviruses (Prasad et al., 2020). Four classes of enveloping protein S, N, M, E maintain the surface structure that involves in the life cycle of the viral particles (Satarker et al., 2020).  The appearance of SARS-CoV-2 in 2019 has more affinity to the receptor to enter into host cell making it more infectious rather than SARS coronavirus 2003 (Berry et. al., 2004).

Vaccine

Vaccines are the most widely accepted and effective treatment to control any of the viral or bacterial or fungal pandemic to restore the global economy (Richner et al., 2017; Pardi et al., 2017). To develop a vaccine needed of genetic information of that parasite so the viral pandemic by the coronavirus in 2019 sequenced in January 2020, With-in months of emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is composed of a positive-stranded RNA genome of 29891 nucleotides with 9860 amino acids (Chan et al., 2020). World Health Organization (WHO) declared the COVID-19 infection as pandemic on 11 March 2020 (https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020). SARS infection results in activation of T-helper (Th1) cell-mediated immunity and hyper innate inflammatory 872 Hui & Zumla response. Delayed or less active innate and acquired immune response enable the coronavirus and mild disease to leads to cytokine dysregulation, viral cytopathic effects, down-regulation of lung ACE 2, abnormal immune responses, and autoimmune mechanisms may be jumped moderate to the severe stage and caused death (Nicholls et al., 2003; Peiris et al., 2003). Rhesus Macaques trial of SARS-CoV-specific immune responses of the adenoviral-based vaccine against COVID-19 could be applied on humans (Gao et al., 2003). A DNA-based vaccine immunity production in mice found a seroconversion of 3 doses of immunization is 75% (Zhao et al., 2004). Spike protein gene-containing plasmid DNA vector leads to humoral immune responses which reduce viral multiplication (Yang et al., 2004). Antigenicity and receptor-binding ability can be developed by recombinant Spike protein, while specific antibodies against SARS-CoV S protein might provide by synthetic peptides eliciting another approach for further developing SARS vaccine (Hui et al., 2019).

Live strain imprint of coronavirus could longer of time at room temperature (Lai et al., 2005). To detection of coronavirus, we found monoclonal antibodies antibody against the surface structural N protein was found to be a sensitive assay for the diagnosis of SARS furthermore EIA detection of SARS N was performed using a panel of three monoclonal antibodies (Che et al., 2005). Passive immunization is done by plasma donors who are procured by COVID-19 infection, with high titers of neutralizing antibody with no side effects (Cheng et al., 2005; Yeh et al., 2005). A recent view of researcher suggests hyperimmune globulin which is produced from severe patients and equine plasma by immunization with inactivated SARS-CoV are available for prophylactic trials in humans (Lu et al., 2005; Zhang et al., 2005). A potent cross-reactive monospecific polyclonal antibodies against the spike protein conservative sequences, able to neutralize epidemic SARS-CoV-2 of 2019 (He et al., 2006; Zhu et al., 2007). A chimeric form of attenuated parainfluenza virus–SARS-CoV virus resulted in better immune response and decreases the duplication of SARS-CoV-2 in the upper and lower respiratory tract (Bukreyev et al., 2007). Active immunization expected, the importance of the Spike protein was confirmed in the murine model of highly attenuated modified vaccinia virus Ankara carrying the S protein (Bisht et al., 2004). The above structural and transmission investigation of the COVID-19 virus suggest that the vaccines could develop by several types of immunogen listed below (table-1) with respective selected widely efficient vaccine by WHO.

Table-1: Specific selected WHO-approved various immunogen-based, COVID-19 pandemic developed vaccines to neutralise SARS-CoV-2 virus, are listed with their trade name.

Covishiled/AZD1222

Instead of covishield AZD1222 (Astra Zeneca, ChAdOx1) 48 more COVID-19 immune booster doses are under clinical progress. Out of the 11 are possess good immunogen in respect to immune response efficiency currently being evaluated in the third stage of clinical investigation (https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf?ua=1). Oxford University research intelligence was successfully establish a COVID-19 specific antibody by using a replication-deficient chimpanzee that containing an adenoviral vector with spike glycoprotein; (nCoV-19) gene (Voysey et al., 2021). Adenoviral vector is taken for the development of covishield for better expression of antigen-presenting cells CD4+ and CD8+ even in the absence of an adjuvant, that intense a strong cellular immune power (Ura et al., 2014). On April 23, 2020, has started the clinical trial in phase 1 across the UK(COV001), later randomise in the UK, Brazil, and South Africa, named COV002, COV003, COV005 respectively. In phase 1/2 clinical trial (NCT04324606) 5 adult COV001 and 6 older COV002 specimen are selectively published with safety features after the incubation of trial doses. Phase 3 clinical trial raised number of volunteers seems to be the perfection of immunogenicity and belief system in the population (Folegatti et al., 2020; Ramasamy et al., 2020; Barrett et al., 2021). The IgG antibody response peaked at end of the month which is multiplied by a second dose seen to neutralization response 91% in the first dose and 100% after the second booster dose (Folegatti et al., 2020). The maximum efficacy obtained was 90% by lowering the first dose followed by a full of the second dose of 0.5mL. In the next trial full amount of 0.5mL of both doses lowered the immune response to 62.1%. Thus overall efficacy amount incubated individuals seem to be 70.4%. Instant of this result Astra Zeneca has assigned with the US, EU, UK, India, China, Thailand, The Philippines, and Australia (Prüβ et al., 2021).

Covaxin/BBV152

COVID-19 strain NIV-2020-770, spike protein is sufficient to develop BBV152 Covaxin vaccine. Bharat Biotech is developed BBV152 vaccine in collaboration with the Indian Council of Medical Research (ICMR)-National Institute of Virology (NIV). Substitution of aspartic into glycine amino acid at locus 614 results in increased immunogenicity of the spike protein. In-vivo isolation of coronavirus strain NIV-2020-770 occurred in ‘Vero CCL-81’ cells genetic information with nucleotide sequence submitted to GISAID (EPI_ISL_420545) (Sarkale et al., 2020). In this vaccine, drive founds the development of a functionally inactive virion dependent vaccine against SARS-CoV-2 named BBV152 has a neutralizing antibody immune response to hCoV-19/India/2020770 (homologous), and two heterologous strains hCoV-19/India/2020Q111 and hCoV-19/India/2020Q100 in phase 1 clinical trial (Ella et al., 2021). They were also found a substitution mutation L3606F at locus 3606 of functional gene “open reading frame 1ab5” in both above mentioned homologous and heterologous strains (Sapkal et al., 2020). Plaque reduction neutralization (PRNT50)-based assay, the test of neutralizing antibodies immune response being 98.6% after incubation of first 6 microgram and second 3 microgram doses within 28 days interval with imidazoquinoline (Ella et al., 2020). Vaccine efficacy against all variant related COVID-19 disease 71% and further differ for a different types of corona variant. The sera test of vaccine recipients could find potential escape by neutralization of all existing UK variant strains with recent mutation 501Y leads to advantage of the indigenous BBV152/COVAXIN (Sapkal et al., 2020).

Janssen/Ad26.COV2.S

Recombinant vector-based stable immune booster dose developed by a replication-incompetent recombinant adenovirus type 26 (Ad26) vector expressing the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike (S) protein (Winslow et al., 2017). It is colorless, visible particulates, and opalescent sterile vaccine route into intramuscular. The Ad26 vector expressing the SARS-CoV-2 S protein is grown in PER.C6 TetR cells, into amino acids containing culture media. In next the vaccine is processed through several purification steps, formulated with inactive ingredients: citric acid monohydrate (0.14 mg), trisodium citrate dehydrate (2.02 mg), ethanol (2.04 mg), 2-hydroxypropyl-β-cyclodextrin (HBCD) (25.50 mg), polysorbate-80 (0.16 mg), sodium chloride (2.19 mg) and filled into vials. Due to high immunogenicity efficiency, there is only a single dose incubated into the recipient. Janssen COVID-19 Vaccine does not contain a preservative. Adenovirion Vector expresses the SARS-CoV-2 spike (S) protein that’s enough to work as a strong immunogen result human body immune response protects against COVID-19. Vaccine efficacy against severe/critical COVID-19 at least 14 days after vaccination was 76.7% (95% CI: 54.6; 89.1) and 85.4% (95% CI: 54.2; 96.9) at least 28 days after vaccination. The concordance vaccine efficacy rate into a subgroup of all existing SARS-CoV-2 variants against moderate to severe/critical COVID-19 and severe/critical COVID-19 for Brazil, South Africa, and the United States were conducted up to the data cut-off date between the PCR results from the local laboratory and the central laboratory was observed 90.3%. Janssen COVID-19 Vaccine also work as the heterologous booster vaccine dose. A 0.5 mL dose of Janssen COVID-19 Vaccine is applied to incubation, formulated to contain 5×1010 virus particles (VP). It contains the wild-type signal peptide that exhibits potent neutralizing immunity with single immunization administered intranasal or intratracheally minimizes the number of COVID-19 in hamsters and rhesus macaques (Bos et al., 2020; Tostanoski et al., 2020; Mercado et al., 2020).

Moderna/mRNA-1273

On November 30, 2020, ModernaTX was launched by FDA for an investigational COVID-19 mRNA-1273-P301 based vaccine intended to prevent COVID-19 caused by SARS-CoV-2. This vaccine has incubated both doses with an interval of four weeks in 0.5mL quantity in the United States. The Moderna COVID-19 Vaccine is a white to off-white, sterile, preservative-free frozen suspension for intramuscular injection. The vaccine contains a genetically engineered m-RNA-1273-P301 encoding the pre-fusion stabilized spike glycoprotein (S) of SARS-CoV-2 virus against antibody is developed (Corbett et al., 2020). The vaccine following ingredients: lipids (SM-102, 1,2-dimyristoyl-rac-glycero3-methoxypolyethylene glycol-2000 [PEG2000-DMG], cholesterol, and 1,2-distearoyl-snglycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose make it more susceptible (Richner et al., 2017; Hassett et al., 2019). N1-methyl-pseudouridine replaces the uridine to increase the stability of RNA (Anderson et al., 2011).  The Moderna COVID-19 Vaccine, mRNA-1273 (100 μg) is administered intramuscularly as a series of two doses (0.5 mL each), given 28 days apart within 6 hours of opening. FDA has determined that the Sponsor has provided adequate information to ensure the vaccine’s quality and consistency for authorization of the product under EUA (Ledford et al., 2020). Efficacy of the vaccine to prevent COVID-19 occurring at least 14 days after dose 2 was 94.5%, (95% CI 86.5%; 97.8%) in participants without prior evidence of SARS-CoV-2 infection across demographic subgroups were consistent in the overall study population. The major outcome of MODERNA vaccine is to stand hygienic rate to reduce the risk of confirmed COVID-19 within 14 days of the second dose.

Sputnik V/Gam-Covid-Vac

Adenovirus (rAd) type 26 and rAd5 are combined to form a shuttle vector to develop Sputnik V (Gam-COVID-Vac) vector vaccine (Logunov et al., 2020). It was developed by the Gamaleya National Center of Epidemiology and Microbiology. Virus-neutralizing antibodies and SARS-CoV-2 spike immunoglobulin G (IgG) were measured using wild-type (WT) SARS-CoV-2 and a pseudotyped vesicular stomatitis virus (VSV) spike-expressing GFP and enzyme-linked immunosorbent assay respectively (Ojeda et al., 2021; Case et al., 2020). Quantification is done followed by WHO International Standard protocol via different laboratories’ data comparative study (Kristiansen et al., 2021). Specific anti-spike antibody response of 94% and WT virus-neutralizing capacity of 90% leads to 91.6% efficacy against coronavirus disease 2019 (COVID-19) (Logunov et al., 2021; Rossi et al., 2021). A high seroconversion rate just after 21 days of the first dose in naive individuals is a unique feature of Sputnik V. There are two doses of intramuscular Sputnik V routed in 21 days interval leads a fast and robust immune response in seropositive participants. The second dose increases antibody by binding and neutralizing and the T-cell response for CD4+ and CD8+ were observed moderative (Logunov et al., 2020). These initial immune response of the Sputnik V vaccine get approved on 11 August 2020, by Russia to become the first country before third phase trial of vaccine to register a COVID-19 vaccine. This decision was questioned in most of the articles in high-impact journal (Burki et al., 2020; Callaway et al., 2020; Bucci et al., 2020).

Zydus Candila/ZyCoV-D

The most privileged surface protein spike-S gene ligated into plasmid DNA which coded for unit gene only able to establish DNA vaccine Zydus Candila (ZyCoV-D) of SARS-CoV-2. A transformation process is applied to the entry of DNA vector into E-coli host. The spike(S) region of surface protein includes a domain for receptor binding to bind with the human angiotensin-converting enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell (Dey et al., 2021). Intradermal route of DNA vaccine in mice, guinea pig, and rabbit specimen of different doses found to be a potential immunogenic induces antibody response including neutralizing antibodies (NAB) against SARS-CoV-2 and same for MERS ((Dey et al., 2021; Modjarrad et al., 2019; Martin et al., 2008). Instead of SARS DNA vaccine, MERS DNA vaccine is 14% more susceptible in the sense of seroconversion. Zydus Candila is the first DNA vaccine that was tolerated by healthy adults with 66% efficacy. This DNA vaccine incubate immunization with three doses administration within 28 days apart make it first. There are currently several COVID-19 candidate vaccines undergoing pre-clinical, clinical trials globally, including mRNA vaccines, replicating or non-replicating viral vector vaccines, DNA vaccines, autologous dendritic cell-based vaccines, and inactive virus vaccines [7]. The results of Phase 1 and 2 trials of several vaccines have been published and a few of phase 3 trials have also been published now (Baden et al., 2021; Polack et al., 2020). The primary endpoint was the adverse reactions within 7 days after each of the vaccination and the 28th day as safety endpoints. The secondary endpoints included seroconversion based on IgG antibodies and IFN-g cellular immune responses after 3 doses of vaccine (Momin et al., 2021).

Novavax/NVX-CoV2373             

NVX-CoV2373 is a recombinant SARS-CoV-2 vaccine developed by Novavax. A complete surface spike glycoprotein of SARS-CoV-2 (prototype Wuhan-Hu-1 sequence) was used and introduced into a baculovirus instead of adenovirus. MothSpodoptera frugiperda infected by baculovirus to evaluate spike protein and processed followed by chromatographic purification. The NVX-CoV2373 has an adverse effect on CD+ T-cell and induce a neutralising-antibody immune response four-time multiple after 2 dose route intramuscularly in 21 days apart (Keech et al., 2020). The NVX-CoV2373 vaccine efficacy was measured against Covid-19 under the transmission of B.1.351 SARS variant in South Africa (Cele et al., 2021, Tegally et al., 2020). Vaccine efficacy of 49.4% among participants who were seronegative for SARS-CoV-2 at baseline regardless of HIV and 94% of participants without HIV infection, fulfilled the primary objective of the vaccine. Cases of Covid-19 among vaccine recipients were predominantly mild to moderate, with a reported overall vaccine efficacy of 22% (95% CI, −50 to 60) and an efficacy of 10% (95% CI, −77 to 55) against the B.1.351 variant, with the B.1.351 variant making up 95% of cases.25 NVX-CoV2373 SARS vaccine was found as the preliminary source of protection against B.1.351 variant (Shinde et al., 2021).

Pfizer-BioNTech/BNT162b1-2

RNA remains unplugged with host genetic material making RNA an efficient marker for any of them during designing (Sahin et al., 2021; Feldman et al., 2019). Two companies BioNTech and the US pharmaceutical giant Pfizer developed mRNA-based vaccines BNT162b1 and BNT162b2 are widely accepted. Modification of uridine into 1-methylpseudouridine facilitates more sustainable antibody production and protection of itself another reason to accept globally (Pardi et al., 2017). A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. German-based BioNTech command on the production of BNT162b1 product that translates the receptor-binding domain (RBD) of the spike protein and BNT162b2 leads prefusion stabilized membrane-anchored full-length spike protein, which is a modified product of point mutation in two proline amino acids to maintain prefusion conformation. Out of them instead of BNT162b2, BNT162b1 product is preferentially considered a prime target for virus-neutralizing antibodies (Brouwer et al., 2020). BNT162b1 produced IgG antibody and antigen-presenting T cell CD8+ and CD4+ response while BNT162b2 was associated with less systemic reactogenicity with a similar response as BNT162b1 particularly in the 65–85 year age group (Walsh et al., 2020). A two-dose regimen of BNT162b2 was found to be safe and 95% effective against Covid-19. BioNTech/Pfizer has recently received emergency use authorization (EUA) from the FDA and approval by the UK (Tanne et al., 2020; Mahase et al., 2020). Pfizer has contracts with the US, EU, UK, Japan, Canada, and Australia. The rollout of the vaccine has started (Tanne et al., 2020). Pfizer was responsible for the design and conduct of the trial, data collection, data analysis, data interpretation, and the writing of the manuscript. BioNTech was the sponsor of the trial, manufactured the BNT162b2 clinical trial material, and contributed to the interpretation of the data and the writing of the manuscript (Polack et al., 2020).

CoronaVac/ Ad5-nCOV

The first human adenovirus-based two vaccines CanSino Biologics, China and the Ad5-nCOV vaccine by Beijing Institute of Biotechnology China are updated. The Ad5 vector was ligated with the mutant spike glycoprotein gene and the plasminogen activator signal peptide gene (Zhu et al., 2020). Mucosal vaccination trial on mice and ferrets was successful in protecting respiratory tract infection (Wu et al., 2020). The phase 1st trial NCT04313127 of the vaccine has an appropriate immune response to produce antibody and T-cell activation between 2 or 4 weeks (Zhu et al., 2020). The phase 2nd trial NCT04341389 administrated an intramuscular injection with a high dose rather than earlier, (5 × 1010 virus particles) found to be an effective immune response (Zhu et al., 2020). The phase 3rd trial NCT04540419 of a single vaccination with the same dose as phase 2nd leads to the severeness of disease progression, immunogenicity, adverse effects, serum chemistry, and blood counts. The Corona Vac vaccine proposed by Sinovac Biotech is contains inactivated SARS CoV-2 virus with aluminum hydroxide adjuvant. Two doses are routed with 0.5mL apart 14 days. The measurable fact is the titer of neutralizing antibodies and adverse immune effects. A research paper on the Coronavac vaccine published the protocol for an additional phase 3rd trial (NCT04456595) in Brazil (Palacios et al., 2020). Ad5-nCOV and CoronaVac vaccine has 63.7% and 51% efficacy overall while 100% in severe.

Table-2: An indigenous summary of the above detail described most wide accepted WHO listed specific COVID-19 corona vaccine with their name, manufacturing company, amount or number of doses, route site, production country, etc. essential health worker parameters.

Conclusion

At present scenario of COVID-19 due to SARS has continued to threaten due to their ecological insensitive and unstable mutant variant continuously affecting humans with no age restriction. Even after successful genome sequencing and efficient vaccines development, scientist can’t overcome the worldwide SARS-CoV-2 pandemic. Different biomarker-based mRNA-1273, BNT162b1/2, Sputnik V vaccines are found superior as their role of immune response after booster doses. Currently, most of the vaccines are under phase 3rd clinical trial which was routed intradermal and intramuscularly is sufficient to understand corona reaction and incomplete efficacy of the developed vaccine. This study refers to the need to focus on similar or percentages of similarity in different mutant corona variant basis vaccine development with another site of the route may stop reoccurrences of COVID-19 infection and regular economic losses. This could be applied to all upcoming or existing strains of coronavirus with near 100% efficacy.

References

1. Lederberg, J., Hamburg, M. A., & Smolinski, M. S. (Eds.). (2003). Microbial threats to health: emergence, detection, and response.
2. Peiris, J. S., Guan, Y., & Yuen, K. Y. (2004). Severe acute respiratory syndrome. Nature medicine, 10(12), S88-S97.
3. Zhong, N. S., Zheng, B. J., Li, Y. M., Poon, L. L. M., Xie, Z. H., Chan, K. H., … & Guan, Y. (2003). Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. The Lancet, 362(9393), 1353-1358.
4. Xu, R. H., He, J. F., Evans, M. R., Peng, G. W., Field, H. E., Yu, D. W., … & Schnur, A. (2004). Epidemiologic clues to SARS origin in China. Emerging infectious diseases, 10(6), 1030.
5. Peiris, J. S. M., Lai, S. T., Poon, L. L. M., Guan, Y., Yam, L. Y. C., Lim, W., … & SARS Study Group. (2003). Coronavirus as a possible cause of severe acute respiratory syndrome. The Lancet, 361(9366), 1319-1325.
6. Ksiazek, T. G., Erdman, D., Goldsmith, C. S., Zaki, S. R., Peret, T., Emery, S., … & SARS Working Group. (2003). A novel coronavirus associated with severe acute respiratory syndrome. New England journal of medicine, 348(20), 1953-1966.
7. Drosten, C., Günther, S., Preiser, W., Van Der Werf, S., Brodt, H. R., Becker, S., … & Doerr, H. W. (2003). Identification of a novel coronavirus in patients with severe acute respiratory syndrome. New England journal of medicine, 348(20), 1967-1976.
8. Zhong, N. S., & Zeng, G. Q. (2003). Our strategies for fighting severe acute respiratory syndrome (SARS). American journal of respiratory and critical care medicine, 168(1), 7-9.
9. Guan, Y., Zheng, B. J., He, Y. Q., Liu, X. L., Zhuang, Z. X., Cheung, C. L., … & Poon, L. L. (2003). Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science, 302(5643), 276-278.
10. Peiris, J. S., Yuen, K. Y., Osterhaus, A. D., & Stöhr, K. (2003). The severe acute respiratory syndrome. New England Journal of Medicine, 349(25), 2431-2441.
11. Lee, N., Hui, D., Wu, A., Chan, P., Cameron, P., Joynt, G. M., … & Sung, J. J. (2003). A major outbreak of severe acute respiratory syndrome in Hong Kong. New England Journal of Medicine, 348(20), 1986-1994.
12. World Health Organization. Cumulative number of reported cases (SARS) from 1 February to 27 March 2003. (Accessed April 22, 2003, at http://www.who.int/csr/ sarscountry/2003_03_27.)
13. Ksiazek, T. G., Erdman, D., Goldsmith, C. S., Zaki, S. R., Peret, T., Emery, S., … & SARS Working Group. (2003). A novel coronavirus associated with severe acute respiratory syndrome. New England journal of medicine, 348(20), 1953-1966.
14. Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., … & Xu, J. (2019). XiaoyingGu. Zhenshun Cheng, Ting Yu, Jiaan Xia, Yuan Wei, Wenjuan Wu, XueleiXie, Wen Yin, Hui Li, Min Liu, Yan Xiao, Hong Gao, Li Guo, JungangXie, Guangfa Wang, Rongmeng Jiang, Zhancheng Gao, Qi Jin, Jianwei Wang, Bin Cao. Clinical features of patients infected with, 497-506.
15. Hu, Y., Sun, J., Dai, Z., Deng, H., Li, X., Huang, Q., … & Xu, Y. (2020). Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis. Journal of Clinical Virology, 127, 104371.
16. Zheng, F., Tang, W., Li, H., Huang, Y. X., Xie, Y. L., & Zhou, Z. G. (2020). Clinical characteristics of 161 cases of corona virus disease 2019 (COVID-19) in Changsha. Eur Rev Med Pharmacol Sci, 24(6), 3404-3410.
17. Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B. J., & Jiang, S. (2009). The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nature Reviews Microbiology, 7(3), 226-236.
18. Advice for public [Internet]. Who.int. 2018 [cited 2020 Jun 3]. Link
19. Sajed, A. N., & Amgain, K. (2020). Corona virus disease (COVID-19) outbreak and the strategy for prevention. Europasian Journal of Medical Sciences, 2(1), 1-3.
20. Mesev, E. V., LeDesma, R. A., & Ploss, A. (2019). Decoding type I and III interferon signalling during viral infection. Nature microbiology, 4(6), 914-924.
21. Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., … & Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The lancet, 395(10224), 565-574.
22. Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., … & Pöhlmann, S. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. cell, 181(2), 271-280.
23. Centers for Disease Control and Prevention. (2020). Evidence used to update the list of underlying medical conditions that increase a person’s risk of severe illness from COVID-19. US Dep Heal Hum Serv, 2019, 1-6.
24. Roush, S. W., Murphy, T. V., & Vaccine-Preventable Disease Table Working Group. (2007). Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. Jama, 298(18), 2155-2163.
25. Verhees, R. A. F., Dondorp, W., Thijs, C., Dinant, G. J., & Knottnerus, J. A. (2018). Influenza vaccination in the elderly: is a trial on mortality ethically acceptable?. Vaccine, 36(21), 2991-2997.
26. Sajed, A. N., & Amgain, K. (2020). Corona virus disease (COVID-19) outbreak and the strategy for prevention. Europasian Journal of Medical Sciences, 2(1), 1-3.
27. Li, F. (2016). Structure, function, and evolution of coronavirus spike proteins. Annual review of virology, 3, 237-261.
28. Bakkers, M. J., Lang, Y., Feitsma, L. J., Hulswit, R. J., De Poot, S. A., Van Vliet, A. L., … & De Groot, R. J. (2017). Betacoronavirus adaptation to humans involved progressive loss of hemagglutinin-esterase lectin activity. Cell host & microbe, 21(3), 356-366.
29. Chen, Y., Guo, Y., Pan, Y., & Zhao, Z. J. (2020). Structure analysis of the receptor binding of 2019-nCoV. Biochemical and biophysical research communications, 525(1), 135-140.
30. Siddell, S. G. (1995). The coronaviridae. In The coronaviridae(pp. 1-10). Springer, Boston, MA.
31. Coutard, B., Valle, C., de Lamballerie, X., Canard, B., Seidah, N. G., & Decroly, E. (2020). The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral research, 176, 104742.
32. Prasad, S., Potdar, V., Cherian, S., Abraham, P., Basu, A., & ICMR COVID Team. (2020). Transmission electron microscopy imaging of SARS-CoV-2. The Indian journal of medical research, 151(2-3), 241.
33. Satarker, S., & Nampoothiri, M. (2020). Structural proteins in severe acute respiratory syndrome coronavirus-2. Archives of medical research, 51(6), 482-491.
34. Berry, J. D., Jones, S., Drebot, M. A., Andonov, A., Sabara, M., Yuan, X. Y., … & Plummer, F. (2004). Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus. Journal of virological methods, 120(1), 87-96.
35. Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., … & Diamond, M. S. (2017). Modified mRNA vaccines protect against Zika virus infection. Cell, 168(6), 1114-1125.
36. Pardi, N., Hogan, M. J., Pelc, R. S., Muramatsu, H., Andersen, H., DeMaso, C. R., … & Weissman, D. (2017). Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature, 543(7644), 248-251.
37. Chan, J. F. W., Kok, K. H., Zhu, Z., Chu, H., To, K. K. W., Yuan, S., & Yuen, K. Y. (2020). Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging microbes & infections, 9(1), 221-236.
38. World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19 – 11 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020(accessed April 2, 2020)
39. Nicholls, J. M., Poon, L. L., Lee, K. C., Ng, W. F., Lai, S. T., Leung, C. Y., … & Peiris, J. M. (2003). Lung pathology of fatal severe acute respiratory syndrome. The Lancet, 361(9371), 1773-1778.
40. Peiris, J. S. M., Chu, C. M., Cheng, V. C. C., Chan, K. S., Hung, I. F. N., Poon, L. L., … & HKU/UCH SARS Study Group. (2003). Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. The Lancet, 361(9371), 1767-1772.
41. Gao, W., Tamin, A., Soloff, A., D’Aiuto, L., Nwanegbo, E., Robbins, P. D., … & Gambotto, A. (2003). Effects of a SARS-associated coronavirus vaccine in monkeys. The Lancet, 362(9399), 1895-1896.
42. Zhao, P., Ke, J. S., Qin, Z. L., Ren, H., Zhao, L. J., Yu, J. G., … & Qi, Z. T. (2004). DNA vaccine of SARS-Cov S gene induces antibody response in mice. Acta biochimica et biophysica Sinica, 36(1), 37-41.
43. Yang, Z. Y., Kong, W. P., Huang, Y., Roberts, A., Murphy, B. R., Subbarao, K., & Nabel, G. J. (2004). A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature, 428(6982), 561-564.
44. Hui, D. S., & Zumla, A. (2019). Severe acute respiratory syndrome: historical, epidemiologic, and clinical features. Infectious Disease Clinics, 33(4), 869-889.
45. Lai, M. Y., Cheng, P. K., & Lim, W. W. (2005). Survival of severe acute respiratory syndrome coronavirus. Clinical infectious diseases, 41(7), e67-e71.
46. Che, X. Y., Hao, W., Wang, Y., Di, B., Yin, K., Xu, Y. C., … & Yuen, K. Y. (2004). Nucleocapsid protein as early diagnostic marker for SARS. Emerging infectious diseases, 10(11), 1947.
47. Cheng, Y., Wong, R., Soo, Y. O. Y., Wong, W. S., Lee, C. K., Ng, M. H. L., … & Cheng, G. (2005). Use of convalescent plasma therapy in SARS patients in Hong Kong. European Journal of Clinical Microbiology and Infectious Diseases, 24(1), 44-46.
48. Yeh, K. M., Chiueh, T. S., Siu, L. K., Lin, J. C., Chan, P. K., Peng, M. Y., … & Chang, F. Y. (2005). Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. Journal of Antimicrobial Chemotherapy, 56(5), 919-922.
49. LU, J. H., GUO, Z. M., HAN, W. Y., WANG, G. L., ZHANG, D. M., WANG, Y. F., … & ZHONG, N. S. (2005). Preparation and development of equine hyperimmune globulin F (ab′) 2 against severe acute respiratory syndrome coronavirus 1. Acta Pharmacologica Sinica, 26(12), 1479-1484.
50. Zhang, Z., Xie, Y. W., Hong, J., Zhang, X., Kwok, S. Y., Huang, X., … & SARSIg Group. (2005). Purification of severe acute respiratory syndrome hyperimmune globulins for intravenous injection from convalescent plasma. Transfusion, 45(7), 1160-1164.
51. He, Y., Li, J., Li, W., Lustigman, S., Farzan, M., & Jiang, S. (2006). Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. The Journal of Immunology, 176(10), 6085-6092.
52. Zhu, Z., Chakraborti, S., He, Y., Roberts, A., Sheahan, T., Xiao, X., … & Dimitrov, D. S. (2007). Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. Proceedings of the National Academy of Sciences, 104(29), 12123-12128.
53. Bukreyev, A., Lamirande, E. W., Buchholz, U. J., Vogel, L. N., Elkins, W. R., St Claire, M., … & Collins, P. L. (2004). Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS. The Lancet, 363(9427), 2122-2127.
54. Bisht, H., Roberts, A., Vogel, L., Bukreyev, A., Collins, P. L., Murphy, B. R., … & Moss, B. (2004). Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proceedings of the National Academy of Sciences, 101(17), 6641-6646.
55. DRAFT landscape of COVID-19 candidate vaccines – 20 March 2020. 2020. [Last accessed on 2020 Mar 21]. Available from: https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf?ua=1 .
56. Voysey, M., Clemens, S. A. C., Madhi, S. A., Weckx, L. Y., Folegatti, P. M., Aley, P. K., … & Bijker, E. (2021). Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet, 397(10269), 99-111.
57. Ura, T., Okuda, K., & Shimada, M. (2014). Developments in viral vector-based vaccines. Vaccines, 2(3), 624-641.
58. Folegatti, P. M., Ewer, K. J., Aley, P. K., Angus, B., Becker, S., Belij-Rammerstorfer, S., … & Hamlyn, J. (2020). Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet, 396(10249), 467-478.
59. Ramasamy, M. N., Minassian, A. M., Ewer, K. J., Flaxman, A. L., Folegatti, P. M., Owens, D. R., … & Demissie, T. (2020). Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. The Lancet, 396(10267), 1979-1993.
60. Barrett, J. R., Belij-Rammerstorfer, S., Dold, C., Ewer, K. J., Folegatti, P. M., Gilbride, C., … & Pollard, A. J. (2021). Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses. Nature Medicine, 27(2), 279-288.
61. Folegatti, P. M., Ewer, K. J., Aley, P. K., Angus, B., Becker, S., Belij-Rammerstorfer, S., … & Hamlyn, J. (2020). Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet, 396(10249), 467-478.
62. Prüβ, B. M. (2021). Current state of the first COVID-19 vaccines. Vaccines, 9(1), 30.
63. Sarkale, P., Patil, S., Yadav, P. D., Nyayanit, D. A., Sapkal, G., Baradkar, S., … & Abraham, P. (2020). First isolation of SARS-CoV-2 from clinical samples in India. The Indian journal of medical research, 151(2-3), 244.
64. Ella, R., Reddy, S., Jogdand, H., Sarangi, V., Ganneru, B., Prasad, S., … & Vadrevu, K. M. (2021). Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. The Lancet Infectious Diseases.
65. Sapkal, G. N., Yadav, P. D., Ella, R., Deshpande, G. R., Sahay, R. R., Gupta, N., … & Bhargava, B. (2021). Inactivated COVID-19 vaccine BBV152/COVAXIN effectively neutralizes recently emerged B. 1.1. 7 variant of SARS-CoV-2. Journal of Travel Medicine, 28(4), taab051.
66. Ella, R., Reddy, S., Jogdand, H., Sarangi, V., Ganneru, B., Prasad, S., … & Vadrevu, K. M. (2020). Safety and immunogenicity clinical trial of an inactivated SARS-CoV-2 vaccine, BBV152 (a phase 2, double-blind, randomised controlled trial) and the persistence of immune responses from a phase 1 follow-up report. medRxiv.
67. Winslow, R. L., Milligan, I. D., Voysey, M., Luhn, K., Shukarev, G., Douoguih, M., & Snape, M. D. (2017). Immune responses to novel adenovirus type 26 and modified vaccinia virus Ankara–vectored Ebola vaccines at 1 year. Jama, 317(10), 1075-1077.
68. Bos, R., Rutten, L., van der Lubbe, J. E., Bakkers, M. J., Hardenberg, G., Wegmann, F., … & Schuitemaker, H. (2020). Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. npj Vaccines, 5(1), 1-11.
69. Tostanoski, L. H., Wegmann, F., Martinot, A. J., Loos, C., McMahan, K., Mercado, N. B., … & Barouch, D. H. (2020). Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters. Nature medicine, 26(11), 1694-1700.
70. Mercado, N. B., Zahn, R., Wegmann, F., Loos, C., Chandrashekar, A., Yu, J., … & Barouch, D. H. (2020). Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature, 586(7830), 583-588.
71. Corbett, K. S., Edwards, D. K., Leist, S. R., Abiona, O. M., Boyoglu-Barnum, S., Gillespie, R. A., … & Graham, B. S. (2020). SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature, 586(7830), 567-571.
72. Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., … & Diamond, M. S. (2017). Modified mRNA vaccines protect against Zika virus infection. Cell, 168(6), 1114-1125.
73. Hassett, K. J., Benenato, K. E., Jacquinet, E., Lee, A., Woods, A., Yuzhakov, O., … & Brito, L. A. (2019). Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Molecular Therapy-Nucleic Acids, 15, 1-11.
74. Anderson, B. R., Muramatsu, H., Jha, B. K., Silverman, R. H., Weissman, D., & Karikó, K. (2011). Nucleoside modifications in RNA limit activation of 2′-5′-oligoadenylate synthetase and increase resistance to cleavage by RNase L. Nucleic acids research, 39(21), 9329-9338.
75. Ledford, H. (2020). Moderna COVID vaccine becomes second to get US authorization: Two RNA vaccines will be useful as US infections surge, but the speedy authorizations complicate clinical trials. Nature News.
76. Logunov, D. Y., Dolzhikova, I. V., Zubkova, O. V., Tukhvatullin, A. I., Shcheblyakov, D. V., Dzharullaeva, A. S., … & Gintsburg, A. L. (2020). Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. The Lancet, 396(10255), 887-897.
77. Ojeda, D. S., Gonzalez Lopez Ledesma, M. M., Pallarés, H. M., Costa Navarro, G. S., Sanchez, L., Perazzi, B., … & Gamarnik, A. V. (2021). Emergency response for evaluating SARS-CoV-2 immune status, seroprevalence and convalescent plasma in Argentina. PLoS pathogens, 17(1), e1009161.
78. Case, J. B., Rothlauf, P. W., Chen, R. E., Liu, Z., Zhao, H., Kim, A. S., … & Whelan, S. P. (2020). Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2. Cell host & microbe, 28(3), 475-485.
79. Kristiansen, P. A., Page, M., Bernasconi, V., Mattiuzzo, G., Dull, P., Makar, K., … & Knezevic, I. (2021). WHO International Standard for anti-SARS-CoV-2 immunoglobulin. The Lancet, 397(10282), 1347-1348.
80. Logunov, D. Y., Dolzhikova, I. V., Shcheblyakov, D. V., Tukhvatulin, A. I., Zubkova, O. V., Dzharullaeva, A. S., … & Gam-COVID-Vac Vaccine Trial Group. (2021). Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. The Lancet, 397(10275), 671-681.
81. Rossi, A. H., Ojeda, D. S., Varese, A., Sanchez, L., Ledesma, M. M. G. L., Mazzitelli, I., … & Gamarnik, A. V. (2021). Sputnik V vaccine elicits seroconversion and neutralizing capacity to SARS-CoV-2 after a single dose. Cell Reports Medicine, 2(8), 100359.
82. Logunov, D. Y., Dolzhikova, I. V., Zubkova, O. V., Tukhvatullin, A. I., Shcheblyakov, D. V., Dzharullaeva, A. S., … & Gintsburg, A. L. (2020). Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. The Lancet, 396(10255), 887-897.
83. Burki, T. K. (2020). The Russian vaccine for COVID-19. The Lancet Respiratory Medicine, 8(11), e85-e86.
84. Callaway, E. (2020). Russia’s fast-track coronavirus vaccine draws outrage over safety. Nature, 584(7821), 334-336.
85. Bucci, E., Andreev, K., Björkman, A., Calogero, R. A., Carafoli, E., Carninci, P., … & Viola, A. (2020). Safety and efficacy of the Russian COVID-19 vaccine: more information needed. The Lancet, 396(10256), e53.
86. Dey, A., Rajanathan, C., Chandra, H., Pericherla, H. P., Kumar, S., Choonia, H. S., … & Maithal, K. (2021). Immunogenic Potential of DNA Vaccine candidate, ZyCoV-D against SARS-CoV-2 in Animal Models. bioRxiv.
87. Modjarrad, K., Roberts, C. C., Mills, K. T., Castellano, A. R., Paolino, K., Muthumani, K., … & Maslow, J. N. (2019). Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. The Lancet Infectious Diseases, 19(9), 1013-1022.
88. Martin, J. E., Louder, M. K., Holman, L. A., Gordon, I. J., Enama, M. E., Larkin, B. D., … & VRC 301 Study Team. (2008). A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial. Vaccine, 26(50), 6338-6343.
89. Baden, L. R., El Sahly, H. M., Essink, B., Kotloff, K., Frey, S., Novak, R., … & Zaks, T. (2021). Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. New England Journal of Medicine, 384(5), 403-416.
90. Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., … & Gruber, W. C. (2020). Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New England Journal of Medicine.
91. Momin, T., Kansagra, K., Patel, H., Sharma, S., Sharma, B., Patel, J., … & Parmar, D. (2021). Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India. EClinicalMedicine, 38, 101020.
92. Keech, C., Albert, G., Cho, I., Robertson, A., Reed, P., Neal, S., … & Glenn, G. M. (2020). Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. New England Journal of Medicine, 383(24), 2320-2332.
93. Cele, S., Gazy, I., Jackson, L., Hwa, S. H., Tegally, H., Lustig, G., … & Sigal, A. (2021). Escape of SARS-CoV-2 501Y. V2 from neutralization by convalescent plasma. Nature, 593(7857), 142-146.
94. Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., … & de de Oliveira, T. (2020). Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. MedRxiv.
95. Madhi, S. A., Baillie, V., Cutland, C. L., Voysey, M., Koen, A. L., Fairlie, L., … & Izu, A. (2021). Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B. 1.351 variant. New England Journal of Medicine, 384(20), 1885-1898.
96. Shinde, V., Bhikha, S., Hoosain, Z., Archary, M., Bhorat, Q., Fairlie, L., … & Madhi, S. A. (2021). Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B. 1.351 Variant. New England Journal of Medicine, 384(20), 1899-1909.
97. Sahin, U., Karikó, K., & Türeci, Ö. (2014). mRNA-based therapeutics—developing a new class of drugs. Nature reviews Drug discovery, 13(10), 759-780.
98. Feldman, R. A., Fuhr, R., Smolenov, I., Ribeiro, A. M., Panther, L., Watson, M., … & Ciaramella, G. (2019). mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine, 37(25), 3326-3334.
99. Pardi, N., & Weissman, D. (2017). Nucleoside modified mRNA vaccines for infectious diseases. In RNA Vaccines(pp. 109-121). Humana Press, New York, NY.
100. Brouwer, P. J., Caniels, T. G., van der Straten, K., Snitselaar, J. L., Aldon, Y., Bangaru, S., … & van Gils, M. J. (2020). Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science, 369(6504), 643-650.
101. Walsh, E. E., Frenck, R., Falsey, A. R., Kitchin, N., Absalon, J., Gurtman, A., … & Gruber, W. C. (2020). RNA-based COVID-19 vaccine BNT162b2 selected for a pivotal efficacy study. Medrxiv.
102. Tanne, J. H. (2020). Covid-19: FDA panel votes to authorise Pfizer BioNTech vaccine.
103. Mahase, E. (2020). Covid-19: UK approves Pfizer and BioNTech vaccine with rollout due to start next week.
104. Tanne, J. H. (2020). Covid-19: Pfizer-BioNTech vaccine is rolled out in US.
105. Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., … & Gruber, W. C. (2020). Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New England Journal of Medicine.
106. Zhu, F. C., Li, Y. H., Guan, X. H., Hou, L. H., Wang, W. J., Li, J. X., … & Chen, W. (2020). Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. The Lancet, 395(10240), 1845-1854.
107. Wu, S., Zhong, G., Zhang, J., Shuai, L., Zhang, Z., Wen, Z., … & Chen, W. (2020). A single dose of an adenovirus-vectored vaccine provides complete protection of the upper and lower respiratory tracts against SARS-CoV-2 challenge.
108. Zhu, F. C., Guan, X. H., Li, Y. H., Huang, J. Y., Jiang, T., Hou, L. H., … & Chen, W. (2020). Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet, 396(10249), 479-488.
109. Palacios, R., Patiño, E. G., de Oliveira Piorelli, R., Conde, M. T. R. P., Batista, A. P., Zeng, G., … & Gast, C. (2020). Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of treating Healthcare Professionals with the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac–PROFISCOV: A structured summary of a study protocol for a randomised controlled trial. Trials, 21(1), 1-3.