An Outline of Contributing Vaccine Technologies for SARS CoV2
Advancing in Clinical and Preclinical Phase-Trials

Sheikh   Saba   Naz; Iqra      Munir
doi:10.2174/1872208316666220118094344
Abstract

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) is an RNA virus involving 4 structural and 16 non-structural proteins, and exhibiting high transmission potential and fatality. The emergence of this newly encountered beta coronavirus-SARS CoV2 has brought over 2 million people to death, and more than 10 billion people got infected across the globe as yet. Consequently, the global scientific community has contributed to the synthesis and design of effective immunization technologies to combat this virus.
Objectives: This literature review was intended to gather an update on published reports of the vaccines advancing in the clinical trial phases or preclinical trials, to summarize the foundations and implications of contributing vaccine candidates inferring their impact in the pandemic repression. In addition, this literature review distinctly facilitates an outline of the overall vaccine effectiveness at current doses.
Methods: The reported data in this review was extracted from research articles, review articles and patents published from January 2020 to July 2021, available on Google Scholar, Pubmed, Pubmed Central, Research Gate, Science direct, and Free Patent Online Database by using combination of keywords. Moreover, some information is retrieved from native web pages of vaccine manufacturing companies’ due to progressing research and unavailability of published research papers.
Conclusion: Contributing vaccine technologies include: RNA (Ribonucleic acid) vaccines, DNA (Deoxyribonucleic acid) vaccines, viral vector vaccines, protein-based vaccines, inactivated vaccines, viruses-like particles, protein superglue, and live-attenuated vaccines. Some vaccines are prepared by establishing bacterial and yeast cell lines and as self-assembling adenovirus- derived multimeric protein-based self-assembling nanoparticle (ADDOmer). On May 19, WHO has issued an emergency use sanction of Moderna, Pfizer, Sinopharm, AstraZeneca, and Covishield vaccine candidates on account of clinical credibility from experimental data.
Keywords: DNA vaccines, Immunization technologies, RNA vaccines, SARSCoV-2 infection, SARSCoV-2 vaccines.
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Graphical Abstract

[1] 
Wang MY, Zhao R, Gao LJ, Gao XF, Wang DP, Cao JM. SARS-CoV-2: Structure, biology, and structure-based therapeutics development. Front Cell Infect Microbiol  2020; 10: 587269.
[2] 
Ong E, Wong MU, Huffman A, He Y. COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning. bioRxiv  2020; 2020.03.20.000141.
[http://dx.doi.org/10.1101/2020.03.20.000141] 
[3] 
Zhu Z, Lian X, Su X, Wu W, Marraro GA, Zeng Y. From SARS and MERS to COVID-19: a brief sum-mary and comparison of severe acute respiratory in-fections caused by three highly pathogenic human coronaviruses. Respir Res  2020; 21(1): 224.
[http://dx.doi.org/10.1186/s12931-020-01479-w] 
[4] 
Smith EC. The not-so-infinite malleability of RNA viruses: Viral and cellular determinants of RNA virus mutation rates. PLoS Pathog  2017; 13(4): e1006254.
[http://dx.doi.org/10.1371/journal.ppat.1006254] 
[5] 
Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA  2020; 117(21): 11727-34.
[http://dx.doi.org/10.1073/pnas.2003138117] [PMID:  32376634] 
[6] 
Healthcare workers. Centers for disease control and
prevention. 2021. Available from:. https://www.cdc gov/coronavirus/2019-ncov/hcp/clinicalguidancemanagementpatients.
html#:~:text=The
%20incubation %20period %20for %20COVID,from
%20exposure %20to %20symptoms
%20onset.&text=One %20study %20reported
%20that %2097.5,SARS %2DCoV %2D2
%20infection(Accessed July 31, 2021).
[7] 
Coronavirus update (Live): 109,448,208 cases and
2,412,815 deaths from Covid-19 virus pandemic -
worldometer. 2021. Available from:. https://www.-worldometers.info/coronavirus/ (Accessed February
15, 2021.
[8] 
Naz S, Munir I. An overview of the treatment contri-butions measured globally for Covid19 outbreak. Coronaviruses  2021; 2(2): 188-203.
[http://dx.doi.org/10.2174/2666796701999201019154537] 
[9] 
COVID-19 vaccine tracker and landscape. 2021.
Available from:. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidatevaccines (Accessed
July 31, 2021).
[10] 
Wang F, Kream RM. S.jtefano GB. An evidence based perspective on mRNA-SARS-CoV-2 Vaccine Development. Med Sci Monit  2020; 26: e924700.
[http://dx.doi.org/10.12659/MSM.924700] 
[11] 
LaczkA3 D, Hogan MJ, Toulmin SA, et al.. A single immunization with nucleoside-modified mrna vac-cines elicits strong cellular and humoral immune re-sponses against SARS-CoV-2 in mice. Immunity  2020; 53(4): 724-732.e7.
[http://dx.doi.org/10.1016/j.immuni.2020.07.019] [PMID:  32783919] 
[12] 
Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2 - preliminary report. N Engl J Med  2020; 383(20): 1920-31.
[http://dx.doi.org/10.1056/NEJMoa2022483] [PMID:  32663912] 
[13] 
Moderna’s work on a COVID-19 vaccine candidate.
2020. Available from:. https://www.modernatx.com/- modernas-work-potential-vaccine-against-covid-19 (Accessed December 15, 2020).
[14] 
Tai W, Zhang X, Drelich A, et al. A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2. Cell Res  2020; 30(10): 932-5.
[http://dx.doi.org/10.1038/s41422-020-0387-5] [PMID:  32759966] 
[15] 
Skowronski DM, De Serres G. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med  2021; 384(16): 1576-7.
[http://dx.doi.org/10.1056/NEJMc2036242] [PMID:  33596348] 
[16] 
Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature  2020; 586(7830): 594-9.
[http://dx.doi.org/10.1038/s41586-020-2814-7] [PMID:  32998157] 
[17] 
Haas EJ, Angulo FJ, McLaughlin JM, et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cas-es, hospitalisations, and deaths following a nation-wide vaccination campaign in Israel: an observation-al study using national surveillance data. Lancet  2021; 397(10287): 1819-29. published correction appears in Lancet. 2021 Jul 17;398(10296):212
[http://dx.doi.org/10.1016/S0140-6736(21)00947-8] [PMID:  33964222] 
[18] 
CureVac AG. Coronavirus vaccine. U.S. Patents;
20210379181, September 12, 2021.. 
[19] 
Rauch S, Roth N, Schwendt K, Fotin-Mleczek M, Mueller SO, Petsch B. mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents. NPJ Vaccines  2021; 6(1): 57.
[http://dx.doi.org/10.1038/s41541-021-00311-w] [PMID:  33863911] 
[20] 
Kremsner P, Mann P, Bosch J, et al. Phase 1 assess-ment of the safety and immunogenicity of an mRNA- lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers. medRxiv 2020.
[http://dx.doi.org/10.1101/2020.11.09.20228551] 
[21] 
CureVac final data from phase 2b/3 trial of firstgeneration
Covid-19 vaccine candidate, cvncov,
demonstrates protection in age group of 18 to 60.
2021. Available from. https://www.curevac.com/en/2021/06/30/curevac-final-data-from-phase-2b-3-trial-offirst-generation-covid-19-vaccine-candidate-cvncov- -demonstrates-protection-in-age-group-of-18-to-60/ (Accessed August 14, 2021).
[22] 
Zhang NN, Li XF, Deng YQ, et al. A Thermostable mRNA vaccine against COVID-19. Cell  2020; 182(5): 1271-83.e16.
[http://dx.doi.org/10.1016/j.cell.2020.07.024] [PMID:  32795413] 
[23] 
Walvax: mRNA – COVID19 vaccine tracker. 2020.
Available from:. https://covid19.trackvaccines.org/- vaccines/23/ >(Accessed December 19, 2020).
[24] 
Biopharma dealmakers, Arcturus-a clinical-stage
mRNA therapeutics and vaccines company. 2021.
Available from:. https://www.nature.com/articles/d43747-021-00073-3 (Accessed August 1, 2021).
[25] 
Ascending dose study of investigational SARS-CoV-
-2 vaccine ARCT-021 in healthy adult subjects - full
text view - ClinicalTrials.gov. 2020. Available from:. https://clinicaltrials.gov/ct2/show/NCT04480957 (Accessed December 18, 2020).
[26] 
O'dea S, Maguire M. Engineering of dendritic cells
for generation of vaccines against SARS-COV-2.
U.S. Patents; 20210290757, September 23, 2021. . 
[27] 
Richard W.  Dendritic human universal non-antigen
educap vaccine. U.S. Patents; 20220016163, January
20, 2022.. 
[28] 
Providence therapeutics reports supportive preclinical
data for its COVID-19 Vaccine Candidate (PTXCOVID19-
B). 2020. Available from:. https://www. providencetherapeutics.com/providence-therapeutics-reports-supportive-preclinical-data-for-its-covid-19-vaccine-candidate-ptx-covid19-b (Accessed December
19, 2020).
[29] 
Liu J, Budylowski P, Samson R, et al. Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B.medRxiv 2021.[Preprint]. 
[http://dx.doi.org/10.1101/2021.05.11.443286] 
[30] 
Baray JC, Khan MR, Mahmud A, et al. BANCOVID, the first D614G variant mRNA-based vaccine candi-date against SARS-CoV-2 elicits neutralizing anti-body and balanced cellular immune response. Bio-Rxiv 2021.[Preprint]. 
[http://dx.doi.org/10.1101/2020.09.29.319061] 
[31] 
Nag K, Chandra Baray J, Rahman Khan M, et al. An mRNA-based vaccine candidate against SARS-CoV- -2 elicits stable immuno-response with single dose. Vaccine  2021; 39(28): 3745-55.
[http://dx.doi.org/10.1016/j.vaccine.2021.05.035] [PMID:  34039497] 
[32] 
mRNA vaccines. Gennova biopharmaceuticals limited.
2020. Available from: https://gennova.bio/mrnavaccines/ (Accessed December 20, 2020).
[33] 
Kalnin KV, Plitnik T, Kishko M, et al. Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates. 2020.
[http://dx.doi.org/10.1101/2020.10.14.337535] 
[34] 
The first demonstration of virus-like particles expressed
from a modified mRNA cocktail. 2020.
Available from: . https://www.fudan.edu.cn/https://www.fudan.edu.cn/en/2020/0307/c344a104281/page.htm (Accessed December
21, 2020).
[35] 
CNB C. Líneas de actuaciónfrente al SARS-CoV2
enel CNB-CSIC. 2020. Available from:. http://www.cnb.csic.es/index.php/es/investigacion/investigacion-sars-cov2 (Accessed December 22, 2020).
[36] 
Kaur SP, Gupta V. COVID-19 Vaccine: A compre-hensive status report. Virus Res  2020; 288: 198114.
[http://dx.doi.org/10.1016/j.virusres.2020.198114] 
[37] 
Kaur SP, Gupta V. COVID-19 Vaccine: A comprehensive
status report.  Virus Res  2020; 288: 198114.
[http://dx.doi.org/10.1016/j.virusres.2020.198114] [PMID: 32800805] 
[38] 
Smith TRF, Patel A, Ramos S, et al. Immunogenicity of a DNA vaccine candidate for COVID-19. Nat Commun  2020; 11(1): 2601.
[http://dx.doi.org/10.1038/s41467-020-16505-0] 
[39] 
Mammen MP, Tebas P, Agnes J, et al. Safety and
immunogenicity of INO-4800 DNA vaccine against
SARS-CoV-2: a preliminary report of a randomized,blinded, placebo-controlled, Phase 2 clinical trial in
adults at high risk of viral exposure 2021.
[http://dx.doi.org/10.1101/2021.05.07.21256652] 
[40] 
Clinicaltrials.gov. 2020. Phase II / III Study Of
COVID-19 DNA Vaccine (AG0302-COVID19) -
Full Text View - Clinicaltrials.Gov. online Available
at. https://clinicaltrials.gov/ct2/show/NCT04655625 Accessed
24 December 2020.
[41] 
Clinicaltrials.gov. 2020. Safety And Immunogenicity
Study Of GX-19, A COVID-19 Preventive DNA
Vaccine In Healthy Adults - Full Text View - Clinicaltrials.
Gov. [online] Available at:. https://clinicaltrials. gov/ct2/show/NCT04445389 Accessed 25 December
2020
[42] 
Covid-19 and the SymvivobacTRL Platform. Symvivo.
com.. https://www.symvivo.com/covid-19 Published 2020. Accessed December 26, 2020
[43] 
 Evaluating the safety, tolerability, and immunogenicity
of BACTRL-spike vaccine for prevention of
COVID-19 - Full Text View - ClinicalTrials.gov.
Clinicaltrials.gov. . https://clinicaltrials.gov/ct2/show/NCT04334980 Published 2020. Accessed December 26, 2020
[44] 
CORVax12: SARS-CoV-2 Spike (S) protein plasmid
DNA vaccine trial for COVID-19 (SARS-CoV-2) -
Full Text View - ClinicalTrials.gov. Clinicaltrials.
gov.. https://clinicaltrials.gov/ct2/show/NCT04627675 Published 2020. Accessed December 26, 2020.
[45] 
A clinical trial of a plasmid dna vaccine for COVID-
19 [Covigenix VAX-001] in adults - full text view -
ClinicalTrials.gov. Clinicaltrials.gov.. https://clinicaltrials.gov/ct2/show/NCT04591184 Published 2020. Accessed December 30, 2020.
[46] 
Recruitment update for the phase 1 clinical trial of
entos’ made in Canada DNA vaccine for COVID-19.
2021. Available from:https://www.entospharma.-
 com/news/recruitment-update-for-the-phase-1-
 clinical-trial-of-entos-made-in-canada-dna-vaccineforcovid-
 19.  (Accessed August 2, 2021).
[47] 
 Cambridge-developed SARS-CoV-2 vaccine receives £1.9million from the UK government for the clinical trial. 2020. Available from: . https://www.-cam.ac.uk/research/news/cambridge-developed-sarscov-2-vaccine-receives-ps19million-from-uk-government-for-clinical-trial (Accessed December 27,2020).
[48] 
University N. Universities in Nottingham to play a key role in the development of a potential DNA vaccine against COVID-192020 Avaialble from: https://www.ntu.ac.uk/about-us/news/newsarticles/
2020/04/universities-in-nottingham-to-playakey-
role-in-the-development-of-a-potential-dna-
vaccine-against-covid-19 (Accessed December 28,
2020).
[49] 
Rabaan AA, Al-Ahmed SH, Sah R, et al. Recent ad-vances in vaccine and immunotherapy for COVID-19. Hum Vaccin Immunother  2020; 16(12): 3011-22.
[http://dx.doi.org/10.1080/21645515.2020.1825896] [PMID:  33156739] 
[50] 
News Events - BioNet. 2020. Available from:. http://www.bionet-asia.com/media/news-events/ (
Accessed December 29, 2020).
[51] 
Norheim G, Stubsrud E, Skullerud LM, et al. bioRxiv 2020.
[http://dx.doi.org/10.1101/2020.12.08.416875] 
[52] 
Positive preclinical results from vaccine candidates
for COVID-19. Applied DNA Sciences. 2020. Available
from:. https://adnas.com/covid19-vaccines/ (Accessed
December 29, 2020).
[53] 
The University of Waterloo developing DNA-based
COVID-19 vaccine | Waterloo Stories. Waterloo Stories.
2020. Available from:. https://uwaterloo.ca/stories/news/university-waterloo-developing-dna-based-covid-19-vaccine (Accessed
December 30, 2020).
[54] 
van Riel D, de Wit E. Next-generation vaccine plat-forms for COVID-19. Nat Mater  2020; 19(8): 810-2.
[http://dx.doi.org/10.1038/s41563-020-0746-0] [PMID:  32704139] 
[55] 
Barrett JR, Belij-Rammerstorfer S, Dold C, et al. Ox-ford COVID Vaccine Trial Group. Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody re-sponses. Nat Med  2021; 27(2): 279-88.
[http://dx.doi.org/10.1038/s41591-020-01179-4] [PMID:  33335322] 
[56] 
Voysey M, Clemens SAC, Madhi SA, et al. Oxford COVID Vaccine Trial Group. 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. Lancet  2021; 397(10269): 99-111.
[http://dx.doi.org/10.1016/S0140-6736(20)32661-1] [PMID:  33306989] 
[57] 
Phase III trial of a COVID-19 vaccine of adenovirus
vector in adults 18 years old and above - full text
view - clinicaltrials.gov. Available from:. https://clinicaltrials.gov/ct2/show/NCT04526990 (Accessed January 2, 2021).
[58] 
Zhu FC, Guan XH, Li YH, et al. 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, placebocontrolled, phase 2 trial. Lancet  2020; 396(10249): 479-88.
[http://dx.doi.org/10.1016/S0140-6736(20)31605-6] [PMID:  32702299] 
[59] 
The Lancet: Preliminary results from Russian trials of
vaccine candidates reported. EurekAlert!. 2021.
Available from:. https://www.eurekalert.org/pub_releases/2020-09/tl-tlp090420.php (Accessed January 2, 2021).
[60] 
Logunov DY, Dolzhikova IV, Zubkova OV, et al. 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. Lancet  2020; 396(10255): 887-97.
[http://dx.doi.org/10.1016/S0140-6736(20)31866-3] [PMID:  32896291] 
[61] 
Jones I, Roy P. Sputnik V COVID-19 vaccine candi-date appears safe and effective. Lancet  2021; 397(10275): 642-3.
[http://dx.doi.org/10.1016/S0140-6736(21)00191-4] [PMID:  33545098] 
[62] 
Torjesen I. Covid-19: Third candidate vaccine will be tested in the UK. BMJ  2020; 371: m4451.
[http://dx.doi.org/10.1136/bmj.m4451] 
[63] 
Lederman S, Goebel S, Evans D, Noyce R. Recombinant
Poxvirus Based Vaccine Against SARS-CoV-2
virus. U.S. Patent; 20210260182, August 26,. 2021.
[64] 
GRAd-COV2 vaccine against COVID-19 - Full text
view - ClinicalTrials.gov. 2021. Available from:. https://clinicaltrials.gov/ct2/show/NCT04528641 (Accessed January 5, 2021).
[65] 
Batty CJ, Heise MT, Bachelder EM, Ainslie KM. Vaccine formulations in clinical development for the prevention of severe acute respiratory syndrome coronavirus 2 infection. Adv Drug Deliv Rev  2021; 169: 168-89. Published online ahead of print, 2020 Dec 13
[http://dx.doi.org/10.1016/j.addr.2020.12.006] [PMID:  33316346] 
[66] 
COVID-19 vaccination using a 2nd generation
(E1/E2B/E3-Deleted) Adenoviral-COVID-19 in nor-
140 Recent Patents on Biotechnology, 2022, Vol. 16,
No. 2 Naz and Munir mal healthy volunteers - full
text view - clinicaltrials.- gov. 2021. Available from:. https://clinicaltrials.gov/ct2/show/NCT04591717 (Accessed July 30, 2021).
[67] 
Krammer F. SARS-CoV-2 vaccines in development. Nature  2020; 586(7830): 516-27.
[http://dx.doi.org/10.1038/s41586-020-2798-3] [PMID:  32967006] 
[68] 
A study to evaluate safety and immunogenicity of
DelNS1-nCoV-RBD LAIV for COVID-19 - Full text
view - clinicaltrials.gov. 2021. Available from:. https://clinicaltrials.gov/ct2/show/NCT04809389 (Accessed August 6, 2021).
[69] 
Safety and immunity of Covid-19 aAPC Vaccine -
Full text view - ClinicalTrials.gov. 2021. Available
from:. https://clinicaltrials.gov/ct2/show/NCT04299724 (Accessed August 6, 2021).
[70] 
Immunity and safety of Covid-19 synthetic minigene
vaccine - full text view - clinicaltrials.gov. 2021.
Available from:. https://clinicaltrials.gov/ct2/show/NCT04276896 (Accessed August 6, 2021).
[71] 
Rice A, Verma M, Shin A, et al. A next generation bivalent human Ad5 COVID-19 Vaccine delivering both spike and nucleocapsid antigens elicits Th1 Dominant CD4+, CD8+ T-cell and neutralizing anti-body responses. BioRxiv 2020.
[http://dx.doi.org/10.1101/2020.07.29.227595] 
[72] 
Tregoning JS, Brown ES, Cheeseman HM, et al. Vac-cines for COVID-19. Clin Exp Immunol  2020; 202(2): 162-92.
[http://dx.doi.org/10.1111/cei.13517] [PMID:  32935331] 
[73] 
Dendritic cell vaccine, AV-COVID-19, to prevent
COVID-19 infection - full text view - clinicaltrials.-
gov. 2021. Available from:. https://clinicaltrials.gov/ct2/show/NCT04690387 (Accessed August 7, 2021).
[74] 
Yahalom-Ronen Y, Tamir H, Melamed S, et al. A single dose of recombinant VSV-G-spike vaccine protects against SARS-CoV-2 challenge. Nat Commun  2020; 11(1): 6402.
[http://dx.doi.org/10.1038/s41467-020-20228-7] 
[75] 
FArster R. Fleige H, Sutter G. Published  1959; 2020(Aug): 7.
[http://dx.doi.org/10.3389/fimmu.2020.01959] [PMID:  32849655] 
[76] 
Zaichuk TA, Nechipurenko YD, Adzhubey AA, et al. The challenges of vaccine development against be-tacoronaviruses: Antibody dependent enhancement and sendai virus as a possible vaccine vector. Mol Biol (Mosk)  2020; 54(6): 922-38.
[http://dx.doi.org/10.31857/S0026898420060154] [PMID:  33276356] 
[77] 
Ku MW, Bourgine M. AuthiA(c) P, et al Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models. Cell Host Microbe  2021; 29(2): 236-49.e6.
[http://dx.doi.org/10.1016/j.chom.2020.12.010] [PMID:  33357418] 
[78] 
University of Helsinki and University of Eastern Finland
shareholders in a Finnish COVID vaccine company
| University of Helsinki. 2021. Available from:. https://www.helsinki.fi/en/news/pandemics/university-helsinki-and-university-eastern-finland-shareholders-finnish-covid-vaccine-company (Accessed August 8,
2021).
[79] 
Sanchez-Felipe L, Vercruysse T, Sharma S, et al. A single-dose live-attenuated YF17D-vectored SARSCoV-2 vaccine candidate. Nature  2021; 590(7845): 320-5.
[http://dx.doi.org/10.1038/s41586-020-3035-9] [PMID:  33260195] 
[80] 
Hörner C, Schürmann C, Auste A, et al. A highly im-munogenic and effective measles virus-based Th1-biased COVID-19 vaccine. Proc Natl Acad Sci USA  2020; 117(51): 32657-66.
[http://dx.doi.org/10.1073/pnas.2014468117] [PMID:  33257540] 
[81] 
Loes AN, Gentles LE, Greaney AJ, Crawford KHD, Bloom JD. Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice. Viruses  2020; 12(9): 987.
[http://dx.doi.org/10.3390/v12090987] 
[82] 
UW–Madison, FluGen, Bharat biotech to develop
CoroFlu, a coronavirus vaccine. 2021. Available
from:. https://news.wisc.edu/uw-madison-flugen-bharat-biotech-to-develop-coroflu-a-coronavirusvaccine/ (Accessed January 8, 2021).
[83] 
Press Release - Intravacc. 2021. Available from:. https://www.intravacc.nl/news/intravacc-partners-with- -wageningen-bioveterinary-research-and-utrecht-university-to-develop-an-intranasal-covid-19-vaccine/ (Accessed January 9, 2021).
[84] 
King RG, Silva-Sanchez A, Peel JN, et al. Singledose intranasal administration of AdCOVID elicits system-ic and mucosal immunity against SARS-CoV- -2 in mice. bioRxiv  2020; 2020.10.2020.
[http://dx.doi.org/10.1101/2020.10.10.331348] 
[85] 
Zaichuk TA, Nechipurenko YD, Adzhubey AA, et al. The challenges of vaccine development against be-tacoronaviruses: Antibody dependent enhancement and sendai virus as a possible vaccine vector. Mol Biol  2020; 54: 84-6.
[http://dx.doi.org/10.1134/S0026893320060151] [PMID:  32921819] 
[86] 
GeoVax progresses in coronavirus (COVID-19) vaccine
development program. 2021. Available from:. https://www.geovax.com/news/geovax-progresses-in-coronavirus-covid-19-vaccine-development-program (Accessed January 12, 2021).
[87] 
SARS-CoV-2: DZIF scientists and the development
of vaccines | German Center for Infection Research.
2021. Available from:. https://www.dzif.de/en/sars-cov-2-dzif-scientists-and-development-vaccines (Accessed
January 12, 2021).
[88] 
Home | Stabilitech. 2021. Available from:. https://www.stabilitech.com/ (Accessed January 12,
2021).
[89] 
Valo therapeutics to support development of a Pan –
Coronavirus vaccine | Valo therapeutics LTD. 2021.
Available from:. https://www.valotx.com/article/valo-therapeutics-support-development-pan-coronavirus-vaccine (Accessed January 12, 2021).
[90] 
Kurup D, Wirblich C, Ramage H, Schnell MJ. Rabies virus-based COVID-19 vaccine CORAVAX™ induc-es high levels of neutralizing antibodies against SARS-CoV-2. NPJ Vaccines  2020; 5: 98.
[http://dx.doi.org/10.1038/s41541-020-00248-6] 
[91] 
Swartz R. Episomal expression of potent immunoglobulins
derived from human blood or convalescent
plasma to enable short term vaccination / immunization
to COVID, COVID-19 and mutants and other
pandemic and non-pandemic viruses designed from
rapid FDA approval. U.S. Patents; 20220064265,. 2022.
[92] 
Heath PT, Galiza EP, Baxter DN, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med  2021; 385: 1172-83.
[http://dx.doi.org/10.1056/NEJMoa2107659] 
[93] 
Chang-Monteagudo A, Ochoa-Azze R, et al. A single dose of SARS-CoV-2 FINLAY-FR-1A dimeric-RBD recombinant vaccine enhances neutralization re-sponse in COVID-19 convalescents, with excellent safety profile. A preliminary report of an open-label phase 1 clinical trial. 2021.
[http://dx.doi.org/10.1101/2021.02.22.21252091] 
[94] 
J oshua G, Lianget S. Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. bioRxiv 2021.
[http://dx.doi.org/10.1101/2020.09.24.311027] 
[95] 
Liang Z, Zhu H, Wang X, et al. Adjuvants for coro-navirus vaccines. Front Immunol  2020; 11: 589833.
[http://dx.doi.org/10.3389/fimmu.2020.589833] 
[96] 
Watterson D, Wijesundara D, Modhiran N, et al. Mo-lecular clamp stabilized Spike protein for protection against SARS- CoV-2. 
[http://dx.doi.org/10.21203/rs.3.rs-68892/v1.] 
[97] 
Kuo TY, Lin MY, Coffman RL, et al. Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19. Sci Rep  2020; 10(1): 20085.
[http://dx.doi.org/10.1038/s41598-020-77077-z] 
[98] 
Su QD, Zou YN, Yi Y, et al. Recombinant SARSCoV-2 RBD with a built in T helper epitope induces strong neutralization antibody response. Vaccine  2021; 39(8): 1241-7.
[http://dx.doi.org/10.1016/j.vaccine.2021.01.044] [PMID:  33516600] 
[99] 
Instituto finlay de Vacunas Cuba: FINLAY-FR-2 –
COVID19 vaccine tracker. 2021. Available from:. https://covid19.trackvaccines.org/vaccines/52/ (Accessed
February 5, 2021).
[100] 
Wang N, Shang J, Jiang S, Du L. Subunit vaccines against emerging pathogenic human coronaviruses. Front Microbiol  2020; 11(298)
[http://dx.doi.org/10.3389/fmicb.2020.00298] 
[101] 
Dai L, Zheng T, Xu K, et al. A universal design of Betacoronavirus vaccines against COVID-19, MERS, and SARS. Cell  2020; 182(3): 722-733.e11.
[http://dx.doi.org/10.1016/j.cell.2020.06.035] [PMID:  32645327] 
[102] 
Anhui Zhifei Longcom: RBD-Dimer – COVID19
Vaccine Tracker. Available from:. https://covid19.-trackvaccines.org/vaccines/27/#trial-chictr2000040153-nct04646590 (Accessed February
5, 2021).2021.
[103] 
Fujita R, Hino M, Ebihara T, et al. Efficient produc-tion of recombinant SARS-CoV-2 spike protein using the baculovirus-silkworm system. Biochem Biophys Res Commun  2020; 529(2): 257-62.
[http://dx.doi.org/10.1016/j.bbrc.2020.06.020] [PMID:  32703420] 
[104] 
Sanofi and GSK to join forces in unprecedented vaccine
collaboration to fight COVID-19. 2021. Available
from:. https://www.gsk.com/en-gb/media/- press-releases/sanofi-and-gsk-to-join-forces-in-unprecedented-vaccine-collaboration-to-fight-covid-19/ (Accessed February 5, 2021).
[105] 
Vaccine Program COVAXX. 2021. Available from:. https://www.covaxx.com/vaccine (Accessed February
5, 2021).
[106] 
Keech C, Albert G, Cho I, et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med  2020; 383(24): 2320-32.
[http://dx.doi.org/10.1056/NEJMoa2026920] [PMID:  32877576] 
[107] 
COVID-19 – BaiyaPhytopharm. 2021. Available
from:. https://baiyaphytopharm.com/covid-19/ (Accessed
August 10, 2021).
[108] 
COVID-19 – BaiyaPhytopharm. BaiyaPhytopharm.. https://baiyaphytopharm.com/covid-19/ Published
2021. Accessed August 10, 2021
[109] 
Neo7Logix precision bio-science. Available from:. https://neo7logix.com/ (Accessed February 6,
2021).2021.
[110] 
Malladi SK, Singh R, Pandey S, et al. Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment. J Biol Chem  2021; 296: 100025.
[http://dx.doi.org/10.1074/jbc.RA120.016284] [PMID:  33154165] 
[111] 
Izmir biomedicine and genome center. 2021. Available
from:. https://www.ibg.edu.tr/news/details/- first-animal-tests-for-the-coronavirus-vaccinationgave-positive-results/ (Accessed February 6, 2021).
[112] 
MIGAL’s Coronavirus Vaccine Project | MIGAL -
Galilee Research Institute. 2021. Available from:. https://www.migal.org.il/en/coronavirus-vaccine-project (Accessed February 8, 2021).
[113] 
Liu Z, Xu W, Xia S, et al. The recombinant subunit vaccine RBD-Fc, consisting of SARS-CoV-2 RBD and human IgG Fc as an immunopotentiator, elicits robust neutralizing antibody responses against SARS-CoV-2 infection 2020.
[http://dx.doi.org/10.21203/rs.3.rs-61074/v1] 
[114] 
Adaptvac. Successful manufacture of COVID-19
Cvlp vaccine. 2021. Availoable from:.  https://8b308f56-ce2d-4857-87a8-
461fb5387ef7.filesusr.- 142 Recent Patents on Biotechnology,
2022, Vol. 16, No. 2 Naz and Munir
com/ugd/d53985_9026ed5a52774bf6ad0af2b04b35d
342.pdf (Accessed July 30, 2021).
[115] 
IMV reports update on COVID-19 vaccine program.
2021. Available from:. https://www.imv-inc.com/investors/press-releases/detail/673/imv-reports-update-on-covid-19-vaccine-program Accessed
February 7, 2021).
[116] 
EPV-CoV19: HCW Vaccine - EpiVax, Inc. - informatics,
and immunology. EpiVax, Inc. - informatics
and immunology. 2021. Available from:. https://epivax.com/pipeline/epv-cov19 (Accessed
February 7, 2021).
[117] 
OncoGen researchers propose personalized vaccinomics
strategy for the novel China coronavirus –
OncoGen Timișoara. 2021. Available from:. https://oncogen.ro/oncogen-vaccine-design-for-coronavirus/ (Accessed February 8, 2021).
[118] 
WRAIR announces COVID-19 vaccine candidate,
targets clinical trial date. 2021. Available from: . www.army.mil Available from:https://www.army.mil/article/240023/wrair_announces_-covid_19_vaccine_candidate_targets_clinical_trial_- date (Accessed February 7, 2021).
[119] 
COVID-19. 2021. Available from:. https://www.-.ge-nerex.com/covid-19 (Accessed February 7, 2021).
[120] 
Kim E, Erdos G, Huang S, et al. Microneedle array delivered recombinant coronavirus vaccines: Immu-nogenicity and rapid translational development. EBioMedicine  2020; 55: 102743.
[http://dx.doi.org/10.1016/j.ebiom.2020.102743] [PMID:  32249203] 
[121] 
Heat biologics announces completion of ZVX-60
vaccine cell line for COVID-19. heat biologics. 2021.
Available from: https://www.heatbio.- com/newsmedia/
 news-releases/detail/676/heat-biologicsannounces-
 completion-of-zvx-60-vaccine-cell..  (Accessed
February 7, 2021).
[122] 
Evtushenko EA, Ryabchevskaya EM, Nikitin NA, Atabekov JG, Karpova OV. Plant virus particles with various shapes as potential adjuvants. Sci Rep  2020; 10: 10365.
[http://dx.doi.org/10.1038/s41598-020-67023-4] 
[123] 
Quadram researchers working on the COVID-19 vaccine
join WHO expert groups - Quadram Institute.
Quadram Institute. 2021. Available from; https://quadram.ac.uk/quadram-researchers-working-oncovid-19-vaccine-join-who-expert-groups/(Accessed
February 8, 2021).. 
[124] 
Ren W, Sun H, Gao GF, et al. Recombinant SARSCoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman pri-mates. Vaccine  2020; 38(35): 5653-8.
[http://dx.doi.org/10.1016/j.vaccine.2020.06.066] [PMID:  32651113] 
[125] 
Sanders B, Koldijk M, Schuitemaker H. Inactivated viral vaccines Vaccine Analysis: Strategies.  Princi-ples, and Control 2014; pp. 45-80.
[http://dx.doi.org/10.1007/978-3-662-45024-6_2] 
[126] 
Zhang Y, Zeng G, Pan H, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a ran-domised, double-blind, placebo- controlled, phase 1/2 clinical trial. Lancet Infect Dis  2021; 21(2): 181-92.
[http://dx.doi.org/10.1016/S1473-3099(20)30843-4] [PMID:  33217362] 
[127] 
Tanriover MD. DoŽYanay HL, Akova M, et al. CoronaVac Study Group. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, ran-domised, placebo-controlled, phase 3 trial in Turkey. Lancet  2021; 398(10296): 213-22.
[http://dx.doi.org/10.1016/S0140-6736(21)01429-X] [PMID:  34246358] 
[128] 
Xia S, Duan K, Zhang Y, et al. Effect of an inactivat-ed vaccine Against SARS-CoV-2 on safety and im-munogenicity outcomes: Interim analysis of 2 ran-domized clinical trials. JAMA  2020; 324(10): 951-60.
[http://dx.doi.org/10.1001/jama.2020.15543] [PMID:  32789505] 
[129] 
Xia S, Zhang Y, Wang Y, et al. Safety and immuno-genicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-- controlled, phase 1/2 trial. Lancet Infect Dis  2021; 21(1): 39-51.
[http://dx.doi.org/10.1016/S1473-3099(20)30831-8] [PMID:  33069281] 
[130] 
Sinopharm [Vero Cell]- Inactivated, COVID-19 vaccine.
2021. Available from:. https://www.who.int/publications/m/item/sinopharm-vero-cell-inactivated-covid-19-vaccine (Accessed August 13, 2021).
[131] 
Ella R, Reddy S, Jogdand H, et al. Safety and immu-nogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomized, phase 1 trial. Lancet Infect Dis  2021; 21(7): 950-61.
[http://dx.doi.org/10.1016/S1473-3099(21)00070-0] [PMID:  33705727] 
[132] 
Ella R, Reddy S, Jogdand H, et al. Safety and immu-nogenicity clinical trial of an inactivated SARSCoV-2 vaccine, BBV152 (a phase 2, double-blind, random-ized controlled trial) and the persistence of immune responses from a phase 1 follow-up report. Lancet Infect Dis  2021; 21(7): 950-61.
[http://dx.doi.org/10.1101/2020.12.21.20248643] 
[133] 
Pu J, Yu Q, Yin Z, et al. An in-depth investigation of the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine. BioRxiv 2020.
[http://dx.doi.org/10.1101/2020.09.27.20189548] 
[134] 
COVID-19 VLA2001 Valneva. 2021. Available
from:. https://valneva.com/research-development/- covid-19-vla2001/ (Accessed February 12, 2021).
[135] 
IRCT | A double-blinded, randomized, placebocontrolled
Phase I Clinical trial to evaluate the safety
and immunogenicity of COVID-19 inactivated vaccine
(Shif-Pharmed) in a healthy population. Contributing
Vaccine Technologies for SARS-CoV-2 Recent
Patents on Biotechnology, 2022, Vol. 16, No. 2 143
2021. Available from:. https://en.irct.ir/trial/52701 (Accessed February 12, 2021).
[136] 
Donaldson B, Lateef Z, Walker GF, Young SL, Ward VK. Virus-like particle vaccines: immunology and formulation for clinical translation. Expert Rev Vaccines  2018; 17(9): 833-49.
[http://dx.doi.org/10.1080/14760584.2018.1516552] [PMID:  30173619] 
[137] 
VLP technologies and production platform. 2021.Available from:. https://www.medicago.com/en/technologies/#production-platform (Accessed February 13, 2021).
[138] 
Study of a recombinant coronavirus-like particle
COVID-19 vaccine in adults - full text view - clinicaltrials.
gov. 2021. Available from. https://clinicaltrials.gov/ct2/show/NCT04636697 (Accessed February 13, 2021).
[139] 
Spybiotech 2021. Available from:. https://www.spybiotech.com/media/uploads/files/SpyBiotech_Corporate_Factsheet_Public_V5_-_26.10.20_1.pdf (Accessed February 13, 2021).
[140] 
COVID-19 - Codagenix 2021. Available from:. https://codagenix.com/vaccine-programs/covid-19/ (Accessed February 13, 2021).
[141] 
Wang Y, Yang C, Song Y, et al. Scalable live-attenuated SARS-CoV-2 vaccine candidate demon-strates preclinical safety and efficacy. Proc Natl Acad Sci USA  2021; 118(29): e2102775118.
[http://dx.doi.org/10.1073/pnas.2102775118] [PMID:  34193524] 
[142] 
Moore T, Moore C. HCoV vaccine for improving
immunity against SARS-CoV-2 infection. U.S. Patent;
11058764, July 17, 2022.. 
[143] 
Science. OSIVAX. 2021. Available from:. http://www.osivax.com/science.html (Accessed February
13, 2021).
[144] 
ARTES joins global combat against Corona - ARTES
Biotechnology. 2021. Available from:. https://artes-biotechnology.biz/artes-joins-global-combat- -against-corona/ (Accessed February 13, 2021).
[145] 
Vragniau C. Bufton Jc, Garzoni F, et al Synthetic self-assembling ADDomer platform for highly effi-cient vaccination by the genetically encoded multie-pitope display. Sci Adv  2019; 5(9): eaaw2853.
[http://dx.doi.org/10.1126/sciadv.aaw2853] 
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DOI https://dx.doi.org/10.2174/1872208316666220118094344	Print ISSN 1872-2083
Publisher Name Bentham Science Publisher	Online ISSN 2212-4012
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An Outline of Contributing Vaccine Technologies for SARS CoV2 Advancing in Clinical and Preclinical Phase-Trials

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