Molecular Characterization and Selection of Indigenous SARS-CoV-2 Delta Variant for the Development of the First Inactivated SARS-CoV-2 Vaccine of Pakistan
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethical Statement
2.2. Isolation of Indigenous SARS-CoV-2 Variant/s from the Clinical Samples
2.3. Selection of Vaccine Candidates Based on Phylogeny and Cross Neutralization
2.4. Virus Titration
2.5. Production of Inactivated SARS-CoV-2 Vaccine
2.6. Protein Profile of Viral Antigen
2.7. Immunogenicity Studies in Mice, Rabbits, and Rhesus Macaques
2.8. SARS-CoV-2 Nucleoprotein-Based ELISA
2.9. Micro Neutralization Assay of Mice, Rabbits, and Rhesus Macaques Serum
2.10. Toxicity Test in Rabbits and Mice
2.11. Statistical Analysis
3. Results
3.1. Isolation of Indigenous SARS-CoV-2 Variant/s from the Clinical Samples
3.2. Selection of Vaccine Candidates Based on Phylogeny and Cross Neutralization
3.3. TCID50 of the Vaccine Candidate Virus
3.4. SARS-CoV-2 Inactivated Vaccine Preparation
3.5. Protein Profile of Viral Antigen
3.6. SARS-CoV-2 Nucleoprotein-Based ELISA
3.7. Anti-SARS-CoV-2 Antibody Response in Animal Models
3.8. Micro Neutralization Assay
3.9. Toxicity Test in Rabbits and Mice
3.10. Post-Vaccination Blood Profile of Non-Human Primates
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
Severe acute respiratory syndrome coronavirus 2 | SARS-CoV-2 |
Coronavirus infectious disease 19 | COVID-19 |
Human coronavirus 19 | hCoV-19 |
University of Health Sciences Pakistan | UHSPK3 |
University of Veterinary and Animal Sciences | UVAS |
Spike | S |
Severe acute respiratory syndrome | SARS |
Gross domestic product | GDP |
World Health Organization | WHO |
Nucleoprotein | N |
Variant of Concern | VOC |
Animal research reporting of in vitro experiments | ARRIVE |
African green monkey kidney cells | VERO-E6 |
American-type culture collection | ATCC CRL |
Defense science and technology organization | DESTO |
Dulbeco’s modified eagles media | DMEM |
Fetal bovine serum | FBS |
Micro gram per mililitre | μg/mL |
United States of America | USA |
Viral transport media | VTM |
Polymerase chain reaction | PCR |
Biosafety level 3 | BSL-3 |
Institute of Microbiology | IOM |
Threshold cycle | CT |
Carbon dioxide | CO2 |
National Center for Biotechnology Information | NCBI |
Global Initiative on Sharing All Influenza Data | GISAID |
Mean tissue culture infective dose 50 | TCID50 |
Multiplicity of infection | MOI |
Cytopathic effects | CPE’s |
Revolution per minute | RCF |
Beta propiolactone | BPL |
Polyethersulfone | PES |
Molecular weight cutoff 0 | MWC0 |
Enzyme-linked immune sorbent assay | ELISA |
Albino laboratory-bred strain of house mouse | BALB/c |
Phosphate buffered saline | PBS |
Microlitre | ul |
Horseradish peroxidase | HRP |
Standard unit per dose | SU/dose |
Receptor binding domain | RBD |
Immunoglobulin G | Ig-G |
Neutralizing antibodies | Nab |
Microneutralization test | MNT |
Maximum tolerated dose | MTD |
Day post-vaccination | DPV |
Liver function test | LFT |
Renal function test | RFT |
Novel coronavirus 19 | nCov-19 |
Massanger RNA | mRNA |
Gamma-glutamyltransferase | GGT |
Alanine transaminase | ALT |
Aspartate transaminase | AST |
Serum glutamic pyruvic transaminase | SGPT |
Serum glutamic oxaloacetic transaminase | SGOT |
Albumin/globulin | A/G |
Inhaled nitric oxide | INO |
Beijing institute of biological sciences corona vaccine | BBIBP-CorV |
Intradermal units per milliliter | IU/ml |
Sample to positive ratio | S/P |
White blood cell | WBC |
Lymphocyte | Lym. |
Monocyte | Mon. |
Granulucyte | Gra. |
Red blood cell | RBC |
Mean corpuscular volume | MCV |
Hematocrit | Hct |
Mean corpuscular haemoglobin | MCH |
Mean corpuscular hemoglobin concentration | MCHC |
Red cell distribution width | RDW |
Hemoglobin | Hb |
Thrombochytocrit | THR |
Mean platelet volume | MPV |
Procalcitonin | Pct |
Platelet distribution width | PDW |
Day post vaccine | DPV |
References
- Hossain, M.F.; Hasana, S.; Mamun, A.A.; Uddin, M.S.; Wahed, M.I.I.; Sarker, S.; Behl, T.; Ullah, I.; Begum, Y.; Bulbul, I.J. COVID-19 outbreak: Pathogenesis, current therapies, and potentials for future management. Front. Pharmacol. 2020, 11, 563478. [Google Scholar] [CrossRef] [PubMed]
- Mehla, R.; Kokate, P.; Bhosale, S.R.; Vaidya, V.; Narayanan, S.; Shandil, R.; Singh, M.; Rudramurthy, G.R.; Naveenkumar, C.N.; Bharathkumar, K. A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters. Vaccines 2023, 11, 255. [Google Scholar] [CrossRef] [PubMed]
- Ilyas, N.; Azuine, R.E.; Tamiz, A. COVID-19 pandemic in Pakistan. Int. J. Transl. Med. Res. Public Health 2020, 4, 37–49. [Google Scholar] [CrossRef]
- Smith, K.A. Edward Jenner and the small pox vaccine. Front. Immunol. 2011, 2, 21. [Google Scholar] [CrossRef] [Green Version]
- Costanzo, M.; De Giglio, M.A.; Roviello, G.N. Anti-coronavirus vaccines: Past investigations on SARS-CoV-1 and MERS-CoV, the approved vaccines from BioNTech/Pfizer, Moderna, Oxford/AstraZeneca and others under Development Against SARSCoV-2 Infection. Curr. Med. Chem. 2022, 29, 4–18. [Google Scholar] [CrossRef]
- Gallo–Ramírez, L.E.; Nikolay, A.; Genzel, Y.; Reichl, U. Bioreactor concepts for cell culture-based viral vaccine production. Expert Rev. Vaccines 2015, 14, 1181–1195. [Google Scholar] [CrossRef]
- Röltgen, K.; Nielsen, S.C.; Silva, O.; Younes, S.F.; Zaslavsky, M.; Costales, C.; Yang, F.; Wirz, O.F.; Solis, D.; Hoh, R.A. Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell 2022, 185, 1025–1040.e14. [Google Scholar] [CrossRef]
- Lederer, K.; Bettini, E.; Parvathaneni, K.; Painter, M.M.; Agarwal, D.; Lundgreen, K.A.; Weirick, M.; Muralidharan, K.; Castaño, D.; Goel, R.R. Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals. Cell 2022, 185, 1008–1024.e15. [Google Scholar] [CrossRef]
- Olliaro, P.; Torreele, E.; Vaillant, M. COVID-19 vaccine efficacy and effectiveness—The elephant (not) in the room. Lancet Microbe 2021, 2, e279–e280. [Google Scholar] [CrossRef]
- Jordan, S.C.; Shin, B.-H.; Gadsden, T.-A.M.; Chu, M.; Petrosyan, A.; Le, C.N.; Zabner, R.; Oft, J.; Pedraza, I.; Cheng, S. T cell immune responses to SARS-CoV-2 and variants of concern (Alpha and Delta) in infected and vaccinated individuals. Cell. Mol. Immunol. 2021, 18, 2554–2556. [Google Scholar] [CrossRef]
- Farrag, M.A.; Almajhdi, F.N. Human respiratory syncytial virus: Role of innate immunity in clearance and disease progression. Viral Immunol. 2016, 29, 11–26. [Google Scholar] [CrossRef]
- Hartl, D.; Tirouvanziam, R.; Laval, J.; Greene, C.M.; Habiel, D.; Sharma, L.; Yildirim, A.Ö.; Cruz, C.S.D.; Hogaboam, C.M. Innate immunity of the lung: From basic mechanisms to translational medicine. J. Innate Immun. 2018, 10, 487–501. [Google Scholar] [CrossRef]
- Khandia, R.; Singhal, S.; Alqahtani, T.; Kamal, M.A.; Nahed, A.; Nainu, F.; Desingu, P.A.; Dhama, K. Emergence of SARS-CoV-2 Omicron (B. 1.1. 529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic. Environ. Res. 2022, 209, 112816. [Google Scholar] [CrossRef]
- Lei, S.; Gao, X.; Sun, Y.; Yu, X.; Zhao, L. Gas chromatography-mass spectrometry method for determination of β-propiolactone in human inactivated rabies vaccine and its hydrolysis analysis. J. Pharm. Anal. 2018, 8, 373–377. [Google Scholar] [CrossRef]
- Perera, R.A.; Ko, R.; Tsang, O.T.; Hui, D.S.; Kwan, M.Y.; Brackman, C.J.; To, E.M.; Yen, H.-l.; Leung, K.; Cheng, S.M. Evaluation of a SARS-CoV-2 surrogate virus neutralization test for detection of antibody in human, canine, cat, and hamster sera. J. Clin. Microbiol. 2021, 59, e02504-20. [Google Scholar] [CrossRef]
- Reed, L.J.; Muench, H. A simple method of estimating 50% endpoints. Am. J. Hyg. 1938, 27, 493–497. [Google Scholar]
- Zhao, F.; Liu, L.; Xu, M.; Shu, X.; Zheng, L.; Wei, Z. Assessments of different inactivating reagents in formulating transmissible gastroenteritis virus vaccine. Virol. J. 2020, 17, 163. [Google Scholar] [CrossRef]
- Pavel, S.T.I.; Yetiskin, H.; Uygut, M.A.; Aslan, A.F.; Aydın, G.; İnan, Ö.; Kaplan, B.; Ozdarendeli, A. Development of an inactivated vaccine against SARS-CoV-2. Vaccines 2021, 9, 1266. [Google Scholar] [CrossRef]
- Wernike, K.; Aebischer, A.; Michelitsch, A.; Hoffmann, D.; Freuling, C.; Balkema-Buschmann, A.; Graaf, A.; Müller, T.; Osterrieder, N.; Rissmann, M. Multi-species ELISA for the detection of antibodies against SARS-CoV-2 in animals. Transbound. Emerg. Dis. 2021, 68, 1779–1785. [Google Scholar] [CrossRef]
- Bennett, R.S.; Postnikova, E.N.; Liang, J.; Gross, R.; Mazur, S.; Dixit, S.; Kocher, G.; Yu, S.; Georgia-Clark, S.; Gerhardt, D. Scalable, Micro-Neutralization Assay for Assessment of SARS-CoV-2 (COVID-19) Virus-Neutralizing Antibodies in Human Clinical Samples. Viruses 2021, 13, 893. [Google Scholar] [CrossRef]
- Swift, M.L. GraphPad prism, data analysis, and scientific graphing. J. Chem. Inf. Comput. Sci. 1997, 37, 411–412. [Google Scholar] [CrossRef]
- Richman, D.D. COVID-19 vaccines: Implementation, limitations and opportunities. Glob. Health Med. 2021, 3, 1–5. [Google Scholar] [CrossRef] [PubMed]
- Forni, G.; Mantovani, A. COVID-19 vaccines: Where we stand and challenges ahead. Cell Death Differ. 2021, 28, 626–639. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Zhang, L.; Liang, Z.; Wang, N.; Liu, S.; Li, T.; Yu, Y.; Cui, Q.; Wu, X.; Nie, J. Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses. Signal Transduct. Target. Ther. 2022, 7, 256. [Google Scholar] [CrossRef] [PubMed]
- Fraiman, J.; Erviti, J.; Jones, M.; Greenland, S.; Whelan, P.; Kaplan, R.M.; Doshi, P. Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults. Vaccine 2022, 40, 5798–5805. [Google Scholar] [CrossRef]
- Basheer, A.; Zahoor, I. Genomic epidemiology of SARS-CoV-2 divulge B. 1, B. 1.36, and B. 1.1. 7 as the most dominant lineages in first, second, and third wave of SARS-CoV-2 infections in Pakistan. Microorganisms 2021, 9, 2609. [Google Scholar] [CrossRef]
- Chen, R.E.; Zhang, X.; Case, J.B.; Winkler, E.S.; Liu, Y.; VanBlargan, L.A.; Liu, J.; Errico, J.M.; Xie, X.; Suryadevara, N. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 2021, 27, 717–726. [Google Scholar] [CrossRef]
- Wang, P.; Nair, M.S.; Liu, L.; Iketani, S.; Luo, Y.; Guo, Y.; Wang, M.; Yu, J.; Zhang, B.; Kwong, P.D. Antibody resistance of SARS-CoV-2 variants B. 1.351 and B. 1.1. 7. Nature 2021, 593, 130–135. [Google Scholar] [CrossRef]
- Sanders, B.; Koldijk, M.; Schuitemaker, H. Inactivated Viral Vaccines. Vaccine Analysis: Strategies, Principles, and Control; Springer: Berlin/Heidelberg, Germany, 2015; pp. 45–80. [Google Scholar]
- He, P.; Zou, Y.; Hu, Z. Advances in aluminum hydroxide-based adjuvant research and its mechanism. Hum. Vaccines Immunother. 2015, 11, 477–488. [Google Scholar] [CrossRef]
- Robbiani, D.F.; Gaebler, C.; Muecksch, F.; Lorenzi, J.C.; Wang, Z.; Cho, A.; Agudelo, M.; Barnes, C.O.; Gazumyan, A.; Finkin, S. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 2020, 584, 437–442. [Google Scholar] [CrossRef]
- Yao, Y.-F.; Wang, Z.-J.; Jiang, R.-D.; Hu, X.; Zhang, H.-J.; Zhou, Y.-W.; Gao, G.; Chen, Y.; Peng, Y.; Liu, M.-Q. Protective efficacy of inactivated vaccine against SARS-CoV-2 infection in mice and non-human primates. Virol. Sin. 2021, 36, 879–889. [Google Scholar] [CrossRef]
- Ganneru, B.; Jogdand, H.; Daram, V.K.; Das, D.; Molugu, N.R.; Prasad, S.D.; Kannappa, S.V.; Ella, K.M.; Ravikrishnan, R.; Awasthi, A. Th1 skewed immune response of whole virion inactivated SARS-CoV-2 vaccine and its safety evaluation. Iscience 2021, 24, 102298. [Google Scholar] [CrossRef]
- Mohandas, S.; Yadav, P.D.; Shete-Aich, A.; Abraham, P.; Vadrevu, K.M.; Sapkal, G.; Mote, C.; Nyayanit, D.; Gupta, N.; Srinivas, V.K. Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS-CoV-2 vaccine candidates in the Syrian hamster model. Iscience 2021, 24, 102054. [Google Scholar] [CrossRef]
- Ganneru, B.; Jogdand, H.; Dharam, V.K.; Molugu, N.R.; Prasad, S.D.; Vellimudu, S.; Ella, K.M.; Ravikrishnan, R.; Awasthi, A.; Jose, J.; et al. Evaluation of safety and immunogenicity of an adjuvanted, TH-1 skewed, whole virion Inactivated SARS-CoV-2 vaccine-BBV152. bioRxiv 2020. [Google Scholar] [CrossRef]
- Wang, H.; Zhang, Y.; Huang, B.; Deng, W.; Quan, Y.; Wang, W.; Xu, W.; Zhao, Y.; Li, N.; Zhang, J. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell 2020, 182, 713–721.e9. [Google Scholar] [CrossRef]
- Muñoz-Fontela, C.; Dowling, W.E.; Funnell, S.G.; Gsell, P.-S.; Riveros-Balta, A.X.; Albrecht, R.A.; Andersen, H.; Baric, R.S.; Carroll, M.W.; Cavaleri, M. Animal models for COVID-19. Nature 2020, 586, 509–515. [Google Scholar] [CrossRef]
- Yadav, P.D.; Ella, R.; Kumar, S.; Patil, D.R.; Mohandas, S.; Shete, A.M.; Vadrevu, K.M.; Bhati, G.; Sapkal, G.; Kaushal, H. Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques. Nat. Commun. 2021, 12, 1386. [Google Scholar] [CrossRef]
- Gao, Q.; Bao, L.; Mao, H.; Wang, L.; Xu, K.; Yang, M.; Li, Y.; Zhu, L.; Wang, N.; Lv, Z. Development of an inactivated vaccine candidate for SARS-CoV-2. Science 2020, 369, 77–81. [Google Scholar] [CrossRef]
- Zhang, C.-h.; Lu, J.-h.; Wang, Y.-f.; Zheng, H.-y.; Xiong, S.; Zhang, M.-y.; Liu, X.-j.; Li, J.-x.; Wan, Z.-y.; Yan, X.-g. Immune responses in Balb/c mice induced by a candidate SARS-CoV inactivated vaccine prepared from F69 strain. Vaccine 2005, 23, 3196–3201. [Google Scholar] [CrossRef]
- Charitos, I.A.; Ballini, A.; Lovero, R.; Castellaneta, F.; Colella, M.; Scacco, S.; Cantore, S.; Arrigoni, R.; Mastrangelo, F.; Dioguardi, M. Update on COVID-19 and Effectiveness of a Vaccination Campaign in a Global Context. Int. J. Environ. Res. Public Health 2022, 19, 10712. [Google Scholar] [CrossRef]
- Lv, Z.; Deng, Y.-Q.; Ye, Q.; Cao, L.; Sun, C.-Y.; Fan, C.; Huang, W.; Sun, S.; Sun, Y.; Zhu, L. Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. Science 2020, 369, 1505–1509. [Google Scholar] [CrossRef] [PubMed]
S.N | Sample ID | Accession Number | Vaccine History | CT |
---|---|---|---|---|
1 | 7442 | MW031799 | Sinopharm (double dose) | 18.82 |
2 | 7501 | MW031800 | Sinopharm (double dose) | 19.6 |
3 | 7542 | MW031801 | Sinopharm (double dose) | 22.0 |
4 | 7549 | MW031802 | Sinopharm (double dose) | 20.1 |
5 | 7305 | MW031803 | Sinopharm (double dose) | 13.37 |
6 | 8523 | - | Sinopharm (double dose) | 15.5 |
7 | 8498 | - | Sinopharm (double dose) | 18.5 |
8 | 8494 | EPIISL548942 | Sinopharm (double dose) | 19.5 |
9 | 7838 | EPIISL548943 | Sinopharm (double dose) | 18.6 |
10 | 7870 | EPIISL548944 | Sinopharm (double dose) | 17.4 |
11 | 7869 | EPIISL548945 | Sinpoharm (double dose) | 19.6 |
12 | 7878 | EPIISL548946 | Sinopharm (double dose) | 17.8 |
13 | 7855 | EPIISL548947 | AstraZenica (1st dose) | 15.2 |
14 | 7846 | EPIISL548948 | Sinovac(1st dose) | 14.9 |
15 | 8643 | - | Sinopharm (double dose) | 17.6 |
16 | 8649 | EPIISL5063601 | Sinovav (double dose) | 19.9 |
17 | 8653 | - | Sinovac (double dose) | 20.5 |
18 | 8842 | - | Sinovac (double dose) | 19.8 |
19 | 8857 | - | Sinopharm (double dose) | 20.4 |
20 | 8910 | - | Sinovac (double dose) | 18.3 |
EPIISL548942 | EPIISL548945 | EPIISL548948 | MW031799 | MW031801 | MW031803 | EPIISL5063601 | |
---|---|---|---|---|---|---|---|
EPIISL548942 serum | 1:16 | 1:8 | 1:4 | 1:64 | 1:32 | 1:32 | 1:16 |
EPIISL548945 serum | 1:32 | 1:64 | 1:128 | 1:64 | 1:64 | 1:32 | 1:128 |
EPIISL548948 serum | 1:32 | 1:128 | 1:128 | 1:64 | 1:512 | 1:128 | 1:64 |
MW031799 serum | 1:16 | 1:64 | 1:128 | 1:8 | 1:64 | 1:32 | 1:16 |
MW031801 serum | 1:4 | 1:32 | 1:16 | 1:256 | 1:128 | 1:64 | 1:64 |
MW031803 serum | 1:32 | 1:8 | 1:16 | 1:128 | 1:8 | 1:32 | 1:4 |
EPIISL5063601 serum | 1:128 | 1:256 | 1:512 | 1:64 | 1:128 | 1:64 | 1:512 |
Factor | Monkey 1 | Monkey 2 | Monkey 3 | Monkey 4 Control | Monkey 5 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0 Day | 7 DPV | 21 DPV | 0 Day | 7 DPV | 21 DPV | 0 Day | 7 DPV | 21 DPV | 0 Day | 7 DPV | 21 DPV | 0 Day | 7 DPV | 21 DPV | |
WBC | 5.4 | 10.2 | 13.16 | 5.3 | 4.56 | 6.06 | 6.67 | 7.27 | 8.21 | 11.06 | 12.92 | 13.2 | 8.2 | 11.4 | 12.73 |
Lym. | 28.6 | 24.3 | 22.7 | 30.1 | 43 | 21.2 | 21.8 | 39.7 | 22.4 | 25 | 24.3 | 25.6 | 9.0 | 11.9 | 12 |
Mon. | 5.2 | 5.1 | 5.3 | 5.6 | 4.6 | 4.4 | 4.5 | 2.3 | 2.4 | 3.4 | 3.0 | 3.6 | 4.1 | 3.4 | 2.2 |
Gra. | 64.5 | 69.2 | 72 | 64.3 | 52.4 | 74.4 | 73.7 | 58 | 75.2 | 71.6 | 67.8 | 72.4 | 65 | 78 | 85.8 |
RBC | 4.65 | 4.56 | 5.44 | 4.51 | 4.22 | 4.49 | 3.97 | 4.94 | 5.02 | 4.56 | 4.61 | 5.2 | 3.85 | 4.3 | 4.96 |
MCV | 82.3 | 78.6 | 70 | 81.1 | 80.3 | 80.6 | 64.4 | 65 | 64 | 63.9 | 66.2 | 65.3 | 58 | 67.9 | 72.8 |
Hct | 35.6 | 39.6 | 38 | 36.5 | 33.8 | 36.1 | 25.5 | 32.1 | 32.1 | 29.1 | 30.5 | 31.9 | 32.1 | 38.9 | 36.1 |
MCH | 23 | 22.8 | 22 | 25.7 | 27 | 25.1 | 22.4 | 20.8 | 20.3 | 19.7 | 19.7 | 21.0 | 18.2 | 22.5 | 23.7 |
MCHC | 32.2 | 33 | 31.5 | 31.7 | 33.7 | 31.3 | 34.9 | 32 | 31.7 | 30.9 | 29.8 | 33 | 35.1 | 36.3 | 32.6 |
RDW | 10.5 | 10.9 | 9.6 | 10.5 | 9.6 | 10.1 | 10 | 11 | 10.6 | 13.6 | 14 | 15.8 | 10.2 | 12.6 | 10.6 |
Hb | 12.3 | 12.0 | 12 | 11.6 | 11.4 | 11.3 | 8.9 | 10.3 | 10.2 | 9 | 9.1 | 8.9 | 8.0 | 12.9 | 11.8 |
THR | 203 | 215 | 199 | 234 | 209 | 292 | 286 | 228 | 266 | 256 | 268 | 292 | 366 | 392 | 297 |
MPV | 8.3 | 8.8 | 8.7 | 8.2 | 9.2 | 8.7 | 8.1 | 8.8 | 8.4 | 7.5 | 8.7 | 7.1 | 8.3 | 8.8 | 9.1 |
Pct | 0.18 | 0.18 | 0.17 | 0.19 | 0.19 | 0.25 | 0.23 | 0.2 | 0.22 | 0.42 | 0.32 | 0.38 | 0.29 | 0.31 | 0.27 |
PDW | 8.2 | 8.1 | 8.3 | 8.8 | 10.1 | 8.5 | 8.1 | 8.3 | 8.8 | 7.1 | 7.5 | 7.9 | 7.8 | 6.9 | 6.6 |
Parameter | M1 | M2 | M3 | M4 | M5 |
---|---|---|---|---|---|
LFT’s | |||||
Bilirubin (Total) | 0.9 | 2 | 0.2 | 1 | 0.7 |
ALT (SGPT) | 24 | 25 | 29 | 22 | 34 |
AST (SGOT) | 50 | 42 | 54 | 35 | 50 |
Alkaline Phosphatase | 339 | 804 | 666 | 265 | 235 |
GGT | 55 | 53 | 65 | 50 | 63 |
Total protein | 9 | 7.3 | 9.2 | 8.1 | 6.2 |
Albumin | 3.9 | 4.1 | 3 | 2.5 | 4.1 |
Globulins | 5.1 | 3.2 | 6.2 | 5.6 | 2.1 |
A/G ratio | 0.76 | 1.2 | 0.48 | 0.44 | 1.9 |
RFT’s | |||||
Creatinine | 0.8 | 0.9 | 0.6 | 0.6 | 0.5 |
Urea | 47 | 68 | 40 | 40 | 39 |
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Aziz, M.W.; Mukhtar, N.; Anjum, A.A.; Mushtaq, M.H.; Shahid, M.F.; Ali, M.; Shabbir, M.A.B.; Ali, M.A.; Nawaz, M.; Yaqub, T. Molecular Characterization and Selection of Indigenous SARS-CoV-2 Delta Variant for the Development of the First Inactivated SARS-CoV-2 Vaccine of Pakistan. Vaccines 2023, 11, 607. https://doi.org/10.3390/vaccines11030607
Aziz MW, Mukhtar N, Anjum AA, Mushtaq MH, Shahid MF, Ali M, Shabbir MAB, Ali MA, Nawaz M, Yaqub T. Molecular Characterization and Selection of Indigenous SARS-CoV-2 Delta Variant for the Development of the First Inactivated SARS-CoV-2 Vaccine of Pakistan. Vaccines. 2023; 11(3):607. https://doi.org/10.3390/vaccines11030607
Chicago/Turabian StyleAziz, Muhammad Waqar, Nadia Mukhtar, Aftab Ahamd Anjum, Muhammad Hassan Mushtaq, Muhammad Furqan Shahid, Muzaffar Ali, Muhammad Abu Bakr Shabbir, Muhammad Asad Ali, Muhammad Nawaz, and Tahir Yaqub. 2023. "Molecular Characterization and Selection of Indigenous SARS-CoV-2 Delta Variant for the Development of the First Inactivated SARS-CoV-2 Vaccine of Pakistan" Vaccines 11, no. 3: 607. https://doi.org/10.3390/vaccines11030607