The World of Vaccines: Phases of Clinical Trials and Current Status of COVID-19 Vaccines


  • Navya Pabbathi Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India
  • Haritha Pasupulati Department of Pharmacy Practice, Bharat Institute of Technology-Pharmacy, Hyderabad, Telangana, India
  • Soni Gaddam Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India
  • Satyanarayana SV Padi Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India



Clinical trials, Clinical evaluation, COVID-19, IA2030, Immunobridging, Seamless design, Vaccine, Vaccine for COVID-19


The world of vaccines has transformed vaccination by saving millions of lives which otherwise would have killed many people and a hurdle for sustainable development world-wide. Indeed, the coronavirus disease 2019 (COVID-19) pandemic is a public health emergency and an important milestone that revealed how vaccines are really turning point for live changing across the world. Owing to extensive human efforts, vaccines for COVID-19 are discovered and developed and approved globally in less than a year, which is the first time in the history of the world of vaccines. Furthermore, one of the strategic goals of WHO’s ‘The Immunization Agenda 2030’ (IA2030) is the clinical development and approval of 500 new vaccines by 2030. Discovery of immunogens that elicit immune responses is a key step or process by which vaccine candidates have been optimized for further preclinical and clinical trials. Clinical evaluation is carried out in Phases (1-3) and is a sequential approach of establishing safety and efficacy in humans. Regulatory requirements for vaccine approval and licensure to bulk manufacturing are another hurdle. Further, post-marketing safety studies and post-marketing surveillance (Phase 4) are essential to collect the real-world data on safety and effectiveness of the approved vaccines. This review work provides a brief outline on timeline of development of traditional and COVID-19 vaccines and summarizes all the six stages of the vaccine development. Furthermore, current status of COVID-19 vaccines is discussed in view of future approvals.



Download data is not yet available.

Author Biographies

Navya Pabbathi, Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India

Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India

Haritha Pasupulati, Department of Pharmacy Practice, Bharat Institute of Technology-Pharmacy, Hyderabad, Telangana, India

Department of Pharmacy Practice, Bharat Institute of Technology-Pharmacy, Hyderabad, Telangana, India

Soni Gaddam, Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India

Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India

Satyanarayana SV Padi, Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India

Department of Pharmacy Practice, Care College of Pharmacy, Hanamkonda, Telangana, 506006, India


1. History of vaccine. Vaccine development, testing, and regulation. (Accessed on 2 May, 2023). Available:
2. The world without vaccines. (Accessed on 2 May, 2023). Available:
3. Meyer H, Ehmann R, Smith GL. Smallpox in the Post-Eradication Era. Viruses. 2020 Jan 24;12(2):138.
4. Henderson DA. The eradication of smallpox-an overview of the past, present, and future. Vaccine. 2011;29 Suppl 4:D7-D9.
5. Nandi A, Shet A. Why vaccines matter: understanding the broader health, economic, and child development benefits of routine vaccination. Hum Vaccin Immunother. 2020;16(8):1900-1904.
6. Carter A, Msemburi W, Sim SY, Gaythorpe KAM, Lindstrand A, Hutubessy RCW. Modeling the impact of vaccination for the immunization agenda 2030: deaths averted due to vaccination against 14 pathogens in 194 countries from 2021-2030. (Accessed on 12 May, 2023). Available:
7. Global Vaccine Action Plan. (Accessed on 20 May, 2023). Available:
8. Immunization Agenda 2030: A global strategy to leave no one behind. (PDF file Accessed on 22 May, 2023). Available:
9. Gaddam S, Pasupulati H, Padi S. Vaccines versus COVID-19 vaccines: Maneuver timeline of development and trial designs. World J Curr Med and Pharm Res. 2023; 5(3):51-61. doi:10.37022/wjcmpr.v5i3.265
10. Williamson ED, Westlake GE. Vaccines for emerging pathogens: prospects for licensure. Clin Exp Immunol. 2019;198(2):170-183.
11. Zhang X, Sharma PK, Peter Goedegebuure S, Gillanders WE. Personalized cancer vaccines: Targeting the cancer mutanome. Vaccine. 2017;35(7):1094-1100.
12. Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20(10):615-632.
13. Singh K, Mehta S. The clinical development process for a novel preventive vaccine: An overview. J Postgrad Med. 2016;62(1):4-11.
14. Puthumana J, Egilman AC, Zhang AD, Schwartz JL, Ross JS. Speed, evidence, and safety characteristics of vaccine approvals by the US food and drug administration. JAMA Intern Med. 2021;181(4):559-560.
15. Han S. Clinical vaccine development. Clin Exp Vaccine Res. 2015;4(1):46-53.
16. Kashte S, Gulbake A, El-Amin Iii SF, Gupta A. COVID-19 vaccines: rapid development, implications, challenges and future prospects. Hum Cell. 2021;34(3):711-733.
17. Kalinke U, Barouch DH, Rizzi R, Lagkadinou E, Türeci Ö, Pather S, Neels P. Clinical development and approval of COVID-19 vaccines. Expert Rev Vaccines. 2022;21(5):609-619.
18. Kesselheim AS, Darrow JJ, Kulldorff M, Brown BL, Mitra-Majumdar M, Lee CC, et al. An overview of vaccine development, approval, and regulation, with implications for COVID-19. Health Aff (Millwood). 2021;40(1):25-32.
19. GAO. Operation Warp Speed: Accelerated COVID-19 vaccine development status and efforts to address manufacturing challenges. (Accessed on 16 May, 2023). Available:
20. Li M, Wang H, Tian L, Pang Z, Yang Q, Huang T, et al. COVID-19 vaccine development: milestones, lessons and prospects. Signal Transduct Target Ther. 2022;7(1):146.
21. Nakagami H, Hayashi H, Shimamura M, Rakugi H, Morishita R. Therapeutic vaccine for chronic diseases after the COVID-19 Era. Hypertens Res. 2021;44(9):1047-1053.
22. Chandrasekharan S, Amin T, Kim J, Furrer E, Matterson AC, Schwalbe N, Nguyen A. Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers. Vaccine. 2015;33(46):6366-70.
23. Cummings J, Lee G, Nahed P, Kambar MEZN, Zhong K, Fonseca J, Taghva K. Alzheimer's disease drug development pipeline: 2022. Alzheimers Dement (N Y). 2022 May 4;8(1):e12295.
24. D'Amico C, Fontana F, Cheng R, Santos HA. Development of vaccine formulations: past, present, and future. Drug Deliv Transl Res. 2021;11(2):353-372.
25. Development and Licensure of Vaccines to Prevent COVID-19. Guidance for Industry. JUNE 2020. (Accessed on 18 May, 2023). Available:
26. Douglas RG, Samant VB. The Vaccine Industry. Plotkin's Vaccines. 2018:41–50.e1.
27. HSP/BIMO Initiative. (Accessed on 20 May, 2023). Available:
28. IND Applications for Clinical Investigations: Regulatory and Administrative Components. (Accessed on 18 May, 2023). Available:
29. Design of vaccine efficacy trials to be used during public health emergencies – points of considerations and key principles. (Accessed on 17 May, 2023). Available:
30. Dean NE, Gsell PS, Brookmeyer R, De Gruttola V, Donnelly CA, Halloran ME, et al. Design of vaccine efficacy trials during public health emergencies. Sci Transl Med. 2019;11(499):eaat0360.
31. Heppner DG Jr, Kemp TL, Martin BK, Ramsey WJ, Nichols R, Dasen EJ, et al. Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study. Lancet Infect Dis. 2017;17(8):854-866.
32. Zhu FC, Zeng H, Li JX, Wang B, Meng FY, Yang F, et al. Evaluation of a recombinant five-antigen Staphylococcus aureus vaccine: The randomized, single-centre phase 1a/1b clinical trials. Vaccine. 2022;40(23):3216-3227.
33. Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro M. Understanding modern-day vaccines: what you need to know. Ann Med. 2018;50(2):110-120.
34. Gast C, Bandyopadhyay AS, Sáez-Llorens X, De Leon T, DeAntonio R, Jimeno J, et al. Fecal Shedding of 2 Novel Live Attenuated Oral Poliovirus Type 2 Vaccine Candidates by Healthy Infants Administered Bivalent Oral Poliovirus Vaccine/Inactivated Poliovirus Vaccine: 2 Randomized Clinical Trials. J Infect Dis. 2022;226(5):852-861.
35. Bukan K, Pearce-Slade T, Eiberg M, Tinelli M, Yahav D, Tuells J, et al. Exclusion of older adults and immunocompromised individuals in influenza, pneumococcal and COVID-19 vaccine trials before and after the COVID-19 pandemic. Aging Clin Exp Res. 2023;35(5):917-923.
36. Tsuchiya Y, Tamura H, Fujii K, Numaguchi H, Toyoizumi K, Liu T, et al. Safety, reactogenicity, and immunogenicity of Ad26.COV2.S: Results of a phase 1, randomized, double-blind, placebo-controlled COVID-19 vaccine trial in Japan. Vaccine. 2023;41(9):1602-1610.
37. Barrett JR, Belij-Rammerstorfer S, Dold C, Ewer KJ, Folegatti PM, Gilbride C, et al. Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses. Nat Med. 2021;27(2):279-288.
38. Walsh EE, Falsey AR, Scott DA, Gurtman A, Zareba AM, Jansen KU, et al. A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine. J Infect Dis. 2022;225(8):1357-1366.
39. Park YC, Ouh YT, Sung MH, Park HG, Kim TJ, Cho CH, et al. A phase 1/2a, dose-escalation, safety and preliminary efficacy study of oral therapeutic vaccine in subjects with cervical intraepithelial neoplasia 3. J Gynecol Oncol. 2019;30(6):e88.
40. Jiang Z, Wang X, Xia J. Considerations on the clinical development of COVID-19 vaccine from trial design perspectives. Hum Vaccin Immunother. 2021;17(3):656-660.
41. Mössler C, Groiss F, Wolzt M, Wolschek M, Seipelt J, Muster T. Phase I/II trial of a replication-deficient trivalent influenza virus vaccine lacking NS1. Vaccine. 2013;31:6194–200.
42. Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how's and what's of vaccine reactogenicity. NPJ Vaccines. 2019;4:39.
43. Burny W, Marchant A, Hervé C, Callegaro A, Caubet M, Fissette L, et al. Inflammatory parameters associated with systemic reactogenicity following vaccination with adjuvanted hepatitis B vaccines in humans. Vaccine. 2019;37(14):2004-2015.
44. Trimble CL, Peng S, Kos F, Gravitt P, Viscidi R, Sugar E, et al. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res. 2009;15(1):361-7.
45. Ward BJ, Gobeil P, Séguin A, Atkins J, Boulay I, Charbonneau PY, et al. Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19. Nat Med. 2021;27(6):1071-1078.
46. Penn-Nicholson A, Tameris M, Smit E, Day TA, Musvosvi M, Jayashankar L, et al. Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial. Lancet Respir Med. 2018;6(4):287-298.
47. Goepfert PA, Fu B, Chabanon AL, Bonaparte MI, Davis MG, Essink BJ, et al. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1-2, dose-ranging study. Lancet Infect Dis. 2021;21(9):1257-1270.
48. Wiedermann U, Garner-Spitzer E, Wagner A. Primary vaccine failure to routine vaccines: Why and what to do? Hum Vaccin Immunother. 2016;12(1):239-43.
49. MacPherson A, Hutchinson N, Schneider O, Oliviero E, Feldhake E, Ouimet C, et al. Probability of Success and Timelines for the Development of Vaccines for Emerging and Reemerged Viral Infectious Diseases. Ann Intern Med. 2021;174(3):326-334.
50. Clinical Development Success Rates 2006–2015. BIO Industry Analysis. June 2016. (Accessed on 16 May, 2023). Available:,%20Biomedtracker,%20Amplion%202016.pdf
51. Vaccine Research & Development. (Accessed on 16 May, 2023). Available:
52. Fast-forward: Will the speed of COVID-19 vaccine development reset industry norms? (Accessed on 19 may, 2023). Available:
53. Adigweme I, Akpalu E, Yisa M, Donkor S, Jarju LB, Danso B, et al. Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-naïve infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial]. Trials. 2022;23(1):775.
54. Harbin A, Laventhal N, Navin M. Ethics of age de-escalation in pediatric vaccine trials: Attending to the case of COVID-19. Vaccine. 2023;41(9):1584-1588.
55. Atuire CA, Salas SP, Wright K, Ambe JR, de Vries J. COVID-19 vaccine trials with children: ethics pointers. BMJ Glob Health. 2022;7(1):e007466.
56. Oneko M, Steinhardt LC, Yego R, Wiegand RE, Swanson PA, Kc N, et al. Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial. Nat Med. 2021;27(9):1636-1645.
57. Steinhardt LC, Richie TL, Yego R, Akach D, Hamel MJ, Gutman JR, et al. Safety, Tolerability, and Immunogenicity of Plasmodium falciparum Sporozoite Vaccine Administered by Direct Venous Inoculation to Infants and Young Children: Findings From an Age De-escalation, Dose-Escalation, Double-blind, Randomized Controlled Study in Western Kenya. Clin Infect Dis. 2020;71(4):1063-1071.
58. Martinón-Torres F, Nolan T, Toneatto D, Banzhoff A. Persistence of the immune response after 4CMenB vaccination, and the response to an additional booster dose in infants, children, adolescents, and young adults. Hum Vaccin Immunother. 2019;15(12):2940-2951.
59. Blehar MC, Spong C, Grady C, Goldkind SF, Sahin L, Clayton JA. Enrolling pregnant women: issues in clinical research. Womens Health Issues. 2013;23(1):e39-45.
60. Kampmann B. Women and children last? Shaking up exclusion criteria for vaccine trials. Nat Med. 2021;27(1):8.
61. Sridhar S, Joaquin A, Bonaparte MI, Bueso A, Chabanon AL, Chen A, et al. Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study. Lancet Infect Dis. 2022;22(5):636-648.
62. Halloran ME, Haber M, Longini IM, Struchiner CJ. Direct and Indirect Effects in Vaccine Efficacy and Effectiveness. Am J Epidemiol. 1991;133(4):323–331.
63. Ishola D, Manno D, Afolabi MO, Keshinro B, Bockstal V, Rogers B, et al. Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial. Lancet Infect Dis. 2022;22(1):97-109.
64. Manno D, Bangura A, Baiden F, Kamara AB, Ayieko P, Kallon J, et al. Safety and immunogenicity of an Ad26.ZEBOV booster dose in children previously vaccinated with the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen: an open-label, non-randomised, phase 2 trial. Lancet Infect Dis. 2023;23(3):352-360.
65. Low EV, Tok PSK, Husin M, Suah JL, Tng BH, Thevananthan T, et al. Assessment of Heterologous and Homologous Boosting With Inactivated COVID-19 Vaccine at 3 Months Compared With Homologous Boosting of BNT162b2 at 6 Months. JAMA Netw Open. 2022;5(8):e2226046.
66. Olwagen CP, Izu A, Mutsaerts EAML, Jose L, Koen A, Downs SL, et al. Single priming and booster dose of ten-valent and 13-valent pneumococcal conjugate vaccines and Streptococcus pneumoniae colonisation in children in South Africa: a single-centre, open-label, randomised trial. Lancet Child Adolesc Health. 2023;7(5):326-335.
67. Madhi SA, Mutsaerts EA, Izu A, Boyce W, Bhikha S, Ikulinda BT, et al. Immunogenicity of a single-dose compared with a two-dose primary series followed by a booster dose of ten-valent or 13-valent pneumococcal conjugate vaccine in South African children: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2020;20(12):1426-1436.
68. Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, et al. 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. Lancet. 2021;396(10267):1979-1993.
69. Frater J, Ewer KJ, Ogbe A, Pace M, Adele S, Adland E, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial. Lancet HIV. 2021;8(8):e474-e485.
70. Hardt K, Vandebosch A, Sadoff J, Le Gars M, Truyers C, Lowson D, et al. Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2): results of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Infect Dis. 2022;22(12):1703-1715.
71. Efficacy Study of GSK's Investigational Respiratory Syncytial Virus (RSV) Vaccine in Adults Aged 60 Years and Above. (Accessed 18 May, 2023). Available:
72. Afolabi MO, Ishola D, Manno D, Keshinro B, Bockstal V, Rogers B, et al. Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2022;22(1):110-122.
73. Pollard AJ, Launay O, Lelievre JD, Lacabaratz C, Grande S, Goldstein N, et al. Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2021;21(4):493-506.
74. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356(19):1915-27.
75. Palacios R, Patiño EG, de Oliveira Piorelli R, Conde MTRP, Batista AP, Zeng G, et al. 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. 2020;21(1):853.
76. Wesselink AK, Hatch EE, Rothman KJ, Wang TR, Willis MD, Yland J, et al. A Prospective Cohort Study of COVID-19 Vaccination, SARS-CoV-2 Infection, and Fertility. Am J Epidemiol. 2022;191(8):1383-1395.
77. Lipsitch M, Jha A, Simonsen L. Observational studies and the difficult quest for causality: lessons from vaccine effectiveness and impact studies. Int J Epidemiol. 2016;45(6):2060-2074.
78. Chen YH, Gesser R, Luxembourg A. A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges. Clin Trials. 2015;12:84–90.
79. Fournillier A, Frelin L, Jacquier E, Ahlén G, Brass A, Gerossier E, et al. A heterologous prime/boost vaccination strategy enhances the immunogenicity of therapeutic vaccines for hepatitis C virus. J Infect Dis. 2013;208(6):1008-19.
80. Barros-Martins J, Hammerschmidt SI, Cossmann A, Odak I, Stankov MV, Morillas Ramos G, et al. Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination. Nat Med. 2021;27(9):1525-1529.
81. Siddiqui A, Adnan A, Abbas M, Taseen S, Ochani S, Essar MY. Revival of the heterologous prime-boost technique in COVID-19: An outlook from the history of outbreaks. Health Sci Rep. 2022;5(2):e531.
82. Rühl J, Citterio C, Engelmann C, Haigh T, Dzionek A, Dreyer J, et al. Heterologous prime-boost vaccination protects against EBV antigen-expressing lymphomas. J Clin Invest. 2019;129(5):2071-2087.
83. Costa Clemens SA, Weckx L, Clemens R, Almeida Mendes AV, Ramos Souza A, Silveira MBV, et al. Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study. Lancet. 2022;399(10324):521-529.
84. Sadoff J, Gray G, Vandebosch A, Cárdenas V, Shukarev G, Grinsztejn B, et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. N Engl J Med. 2021;384(23):2187-2201.
85. Guidance for Industry. Submission of Clinical Trial Application for Evaluating Safety and Efficacy. Document No. - CT/71108. Version – 1. (Accessed on 21 May, 2023). Available:
86. Development & Approval Process (CBER). (Accessed on 21 May, 2023). Available:
87. Adaptive Design Clinical Trials for Drugs and Biologics Guidance for Industry. December 2019. (Download accessed on 19 May, 2023). Available:
88. Emergency Use Authorization. (Accessed on 21 May, 2023). Available:
89. Press Statement by the Drugs Controller General of India (DCGI) on Restricted Emergency approval of COVID-19 virus vaccine. (Accessed on 21 May, 2023). Available:
90. Notice regarding Guidance for approval Covid-19 vaccine in India for restricted use in emergency situation which are already approved for restricted use by US FDA EMA, UK MHRA, PMDA Japan or which are listed in WHO Emergency use listing. (Accessed on 22 Amy, 2023). Available;
91. Cooperative Manufacturing Arrangements for Licensed Biologics. Guidance for Industry. November 2008. (Accessed on 23 May, 2023). Available:
92. Institute of Medicine (US) Committee on the Children's Vaccine Initiative: Planning Alternative Strategies; Mitchell VS, Philipose NM, Sanford JP, editors. The Children's Vaccine Initiative: Achieving the Vision. Washington (DC): National Academies Press (US); 1993. C, Regulatory Aspects of Vaccine Development, Manufacture, and Distribution. (Accessed on 21 May, 2023). Available:
93. Mihigo R, Okeibunor J, Cernuschi T, Petu A, Satoulou A, Zawaira F. Improving access to affordable vaccines for middle-income countries in the African region. Vaccine. 2019;37(21):2838–2842.
94. Pagliusi S, Dennehy M, Homma A. Two decades of vaccine innovations for global public good: report of the developing countries’ vaccine manufacturers network 20th meeting, 21–23 2019, Rio de Janeiro, Brazil. Vaccine. 2020;38:5851–5860.
95. Patil S, Shreffler W. Novel vaccines: technology and development. J Allergy Clin Immunol. 2019;143(3):844–851.
96. Immunization supply chain and logistics: a neglected but essential system for national immunization programmes. (Accessed on 25 May, 2023). Available:
97. Moro PL, Haber P, McNeil MM. Challenges in evaluating post-licensure vaccine safety: observations from the Centers for Disease Control and Prevention. Expert Rev Vaccines. 2019;18(10):1091-1101.
98. Luo J, Wang X, Ma F, Kang G, Ding Z, Ye C, et al. Long-term immunogenicity and immune persistence of live attenuated and inactivated hepatitis a vaccines: a report on additional observations from a phase IV study. Clin Microbiol Infect. 2019;25(11):1422-1427.
99. Khong KW, Zhang R, Hung IF. The Four Ws of the Fourth Dose COVID-19 Vaccines: Why, Who, When and What. Vaccines (Basel). 2022;10(11):1924.
100. Sereti I, Shaw-Saliba K, Dodd LE, Dewar RL, Laverdure S, Brown S, et al. Design of an observational multi-country cohort study to assess immunogenicity of multiple vaccine platforms (InVITE). PLoS One. 2022;17(9):e0273914.
101. Vaccine Effectiveness Studies. (Accessed on 19 May, 2023). Available:
102. Nealon J, Modin D, Ghosh RE, Rudin D, Gislason G, Booth HP, et al. The feasibility of pragmatic influenza vaccine randomized controlled real-world trials in Denmark and England. NPJ Vaccines. 2022;7(1):25.
103. Medeiros-Ribeiro AC, Aikawa NE, Saad CGS, Yuki EFN, Pedrosa T, Fusco SRG, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nat Med. 2021;27(10):1744-1751.
104. Ellsworth GB, Lensing SY, Ogilvie CB, Lee JY, Goldstone SE, Berry-Lawhorn JM, et al. A delayed dose of quadrivalent human papillomavirus vaccine demonstrates immune memory in HIV-1-infected men. Papillomavirus Res. 2018;6:11-14.
105. Lazarus R, Baos S, Cappel-Porter H, Carson-Stevens A, Clout M, Culliford L, et al. Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial. Lancet. 2021;398(10318):2277-2287.
106. Koc ÖM, van Oorschot E, Brandts L, Oude Lashof A. Timing of primary three-dose hepatitis B vaccination and postvaccination serologic testing among a large cohort of healthy adults. J Med Virol. 2022;94(9):4433-4439.
107. What is the difference between efficacy and effectiveness? (Accessed on 17 May, 2023). Available:
108. Olliaro P, Torreele E, Vaillant M. COVID-19 vaccine efficacy and effectiveness-the elephant (not) in the room. Lancet Microbe. 2021;2(7):e279-e280.
109. Liatsikos K, Hyder-Wright A, Pojar S, Chen T, Wang D, Davies K, et al. Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2). BMJ Open. 2022;12(7):e062109.
110. Cohet C, Rosillon D, Willame C, Haguinet F, Marenne MN, Fontaine S, et al. Challenges in conducting post-authorisation safety studies (PASS): A vaccine manufacturer's view. Vaccine. 2017;35(23):3041-3049.
111. Nguyen M, Ball R, Midthun K, Lieu TA. The Food and Drug Administration's Post-Licensure Rapid Immunization Safety Monitoring program: strengthening the federal vaccine safety enterprise. Pharmacoepidemiol Drug Saf. 2012;21 Suppl 1:291-7.
112. Lai LY, Arshad F, Areia C, Alshammari TM, Alghoul H, Casajust P, et al. A Rationale for the EUMAEUS (Evaluating use of methods for adverse events under surveillance-for vaccines) Study Design. Front Pharmacol. 2022;13:837632.
113. Raj N, Fernandes S, Charyulu NR, Dubey A, G S R, Hebbar S. Postmarket surveillance: a review on key aspects and measures on the effective functioning in the context of the United Kingdom and Canada. Ther Adv Drug Saf. 2019;10:2042098619865413.
114. Meher BR. Vaccine pharmacovigilance in India: Current context and future perspective. Indian J Pharmacol. 2019;51(4):243-247.
115. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf. 2009;32(4):309-23.
116. Lee H, Kim HJ, Choe YJ, Shin JY. Signals and trends of Guillain-Barré syndrome after the introduction of live-attenuated vaccines for influenza in the US and South Korean adverse event reporting systems. Vaccine. 2020;38(34):5464-5473.
117. Wachira VK, Farinasso CM, Silva RB, Peixoto HM, Fernandes de Oliveira MR. Incidence of Guillain-Barré syndrome in the world between 1985 and 2020: A systematic review. Global Epidemiol. 2023;5:100098.
118. Ha J, Park S, Kang H, Kyung T, Kim N, Kim DK, et al. Real-world data on the incidence and risk of Guillain-Barré syndrome following SARS-CoV-2 vaccination: a prospective surveillance study. Sci Rep. 2023;13(1):3773.
119. Abara WE, Gee J, Marquez P, Woo J, Myers TR, DeSantis A, et al. Reports of Guillain-Barré Syndrome After COVID-19 Vaccination in the United States. JAMA Netw Open. 2023;6(2):e2253845.
120. Hanson KE, Goddard K, Lewis N, Fireman B, Myers TR, Bakshi N, et al. Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink. JAMA Netw Open. 2022;5(4):e228879.
121. Approved vaccines. Last Updated 3 May 2023. (Accessed on 20 May, 2023). Available:
122. Vaccination rates, approvals & trials by country. Last updated on 3 May, 2023. (Accessed on 20 May, 2023). Available:
123. MOHFW. COVID-19 Vaccination as on 14 June, 2023. Available:
124. Approved COVID-19 vaccines as on 08.07.2022. (Accessed on 24 May, 2023). Available: Upload CDSCOWeb / 2018/ Upload Public_NoticesFiles/Approved %20 COVID-19%20vaccines%20as%20on%2008.07.2022.pdf



How to Cite

Pabbathi, N., Pasupulati, H., Gaddam, S., & SV Padi, S. (2023). The World of Vaccines: Phases of Clinical Trials and Current Status of COVID-19 Vaccines. Asian Journal of Pharmaceutical Research and Development, 11(3), 151–167.