Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand?
Abstract
:1. Introduction
2. A Historical Overview
3. Similarities between SARS-CoV, MERS-CoV, and SARS-CoV-2 in Areas Relevant for Vaccine Design
4. Protective Vaccines against MERS-CoV and SARS-CoV in Animal Models
5. The Potential Role of T Cells in Designing a Vaccine for COVID-19
6. Human Trials on MERS and SARS
SARS | ||||||
---|---|---|---|---|---|---|
Vaccine Platform | Antigen | Administration Method | Country | Trial Phase | Main Primary Outcome Measured | Estimated Study Completion Date or Results |
DNA | Spike gene with truncated cytoplasmic domain | I.M, needle free injection management system | US (n = 10) | Phase I [68] | Safety and immunogenicity | Safe and well tolerated. CD4+ responses detected in all participants, nAb detected in 80% and CD8+ responses in 20% |
Inactivated virus | Whole virion | I.M | China (n = 36) | Phase I [69] | Safety and immunogenicity | Safe and well tolerated. All developed nAb. Peak titer around 2 weeks, but decrease 4 weeks later |
MERS | ||||||
Vaccine Platform | Antigen | Administration Method | Country | Trial Phase | Main Primary Outcome Measured | Estimated Study Completion Date or Results |
Modified vaccinia virus ankara (MVA) vector | Spike | I.M. | Germany (n = 26) | Phase I [72] | Safety and immunogenicity | Safe and well tolerated. 100% S1 Ab and 83–91% T cell response after two immunizations. Development of nAb, but decrease to pre-study levels after 6 months |
DNA | Spike | I.M and E.P | US (n = 75) | Phase I [70] | Safety and immunogenicity | Safe and well tolerated. 94% developed S1 Ab and 76% developed T cell response after three immunizations. nAb was seen in 50% |
Ad-vector | Spike | I.M. | UK/Saudi Arabia (n = 43/24) | Phase I, (NCT03399578/NCT04170829) | Safety and immunogenicity | UK: Safe and well tolerated. Able to generate T cell response as well as IgG. 44% in one group had nAb |
Ad-vector | n.m | I.M. | Russia (n = 162) | Phase I/II, (NCT04130594) | Safety and immunogenicity | December 2020 |
7. Current COVID-19 Trials
7.1. Clinical Trials Using Non-Replicating Viral Vectors
7.2. Clinical Trials Using DNA and mRNA Vaccine
7.3. Clinical Trials Using Inactivated Vaccine
7.4. Clinical Trials Using Protein Subunits
7.5. Clinical Trials Using Antigen-Presenting Cells
7.6. Clinical Trials Investigating the Protective Effects of Already Approved Vaccines
8. What Can We Expect from Current Vaccine Trials When Looking at the Past?
9. Conclusions
Funding
Conflicts of Interest
References
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Vaccine Platform | Antigen | Administration Method | Country | Trial Phase | Main Primary Outcome Measures | Estimated Study Completion Date/Results |
---|---|---|---|---|---|---|
BCG | Non-SARS-CoV-2 | I.D | Australia (n = 4170) | Phase III (NCT04327206) | COVID-19 disease incidence including symptoms and a positive SARS-CoV-2 PCR test | 30 March 2022 |
BCG | Non-SARS-CoV-2 | I.D. | Netherlands (n = 1500) | Phase III (NCT04328441) | Healthcare workers absenteeism | 25 December 2020 |
BCG | Non-SARS-CoV-2 | I.D. | South Africa (n =5500) | Phase III, (NCT04379336) | Healthcare workers morbidity and mortality | 28 April 2021 |
BCG | Non-SARS-CoV-2 | I.D | US (n = 1800) | Phase IV, (NCT04348370) | Healthcare workers, reduction in infection and disease severity | November 2021 |
Antigen presenting cells | Cons. epi | S.C | China (n = 100) | Phase I (NCT04299724) | Frequency of adverse events and serious adverse events and proportion of subjects with positive T cell response | 31 December 2024 |
Lentiviral vector system | Cons. epi | S.C and I.V | China (n = 100) | Phase I/II (NCT04276896) | Clinical improvement based on the seven-point scale Lower Murray lung injury score | 31 December 2024 |
Adenovirus Vector System | FL-S | I.M | China (n = 108) | Phase I (NCT04313127) Phase II (NCT04341389) | Adverse events and immunogenicity | Mild to moderate transient adverse events in 81% of participant. B and T cell response in all participant. Pre-existing Ad immunity diminished vaccine response |
Adenovirus Vector System | FL-S | I.M for comparator, n.m for vaccine | UK (n = 510) | Phase I/II (NCT04324606) | Number of virologically confirmed symptomatic cases and safety | May 2021 |
mRNA | FL-S | I.M | US (n = 105) | Phase I (NCT04283461) | Safety and reactogenicity | 20 September 2021 |
mRNA | n.m | I.M | US (n = 7600) | Phase I/II (NCT04368728) | Local reactions and systemic events | 27 January 2023 |
DNA | S | I.D. and E.P | US (n = 40) | Phase I (NCT04336410) | Adverse events and immunogenicity | April 2021 |
Inactivated vaccine | Whole virion | n.m | China (n = 744/422) | Phase I/II (NCT04352608/NCT04383574) | Adverse events and immunogenicity | 13 December 2020 |
Inactivated vaccine | Whole virion | n.m | China | Phase I/II (ChiCTR2000032459) | Adverse events and immunogenicity | __ |
Inactivated vaccine | Whole virion | n.m | China | Phase I/II (ChiCTR2000031809) | Adverse events and immunogenicity | __ |
Inactivated vaccine | Whole virion | n.m | China (n = 942) | Phase I/II NCT04412538 | Adverse events and immunogenicity | __ |
Protein subunit | rS nano | I.M | Australia (n = 131) | Phase I (NCT04368988) | Adverse events and immunogenicity | 31 July 2021 |
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Al-Kassmy, J.; Pedersen, J.; Kobinger, G. Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand? Viruses 2020, 12, 861. https://doi.org/10.3390/v12080861
Al-Kassmy J, Pedersen J, Kobinger G. Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand? Viruses. 2020; 12(8):861. https://doi.org/10.3390/v12080861
Chicago/Turabian StyleAl-Kassmy, Jawad, Jannie Pedersen, and Gary Kobinger. 2020. "Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand?" Viruses 12, no. 8: 861. https://doi.org/10.3390/v12080861