Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective
Abstract
:1. Introduction
2. Overview of Twelve Vaccines Targeting COVID-19 in Phase III Clinical Trials
Platform [Ref.] | Name (Dose) | Phase III # Enrolled Placebo | Phase III # Enrolled Vaccine | COVID Cases Placebo (Severe) | COVID Cases Vaccine (Severe) | % Efficacy (Severe) | Projected Cost/Dose (USD) |
---|---|---|---|---|---|---|---|
RNA | |||||||
Pfizer/BioNTech [16] | BNT162b2 (2 × 30 μg, 21 days apart) | 21,720 | 21,728 | 162 (9) | 8 (1) | 95 (89) | $14.70–19.50 |
Moderna [17] | mRNA-1273 (2 × 100 μg, 28 days apart) | 15,210 | 15,210 | 185 (30) | 11 (0) | 94.1 (100) | $25–37 |
Viral Vector | |||||||
Astra Zeneca a [18] | AZD1222 (2 × 5×1010 vp, 28 days apart) (2.2 × 1010 vp, then 5 × 1010 28 days apart) | 4455 [1374] | 4440 [1367] | 71 [30] (10/2) | 27 [3] (0/0) | 62.1 (70.4) [90] (100) | $2–10+ |
CanSino b | Ad5-nCoV (Convidecia) (single dose 5 × 1010 vp) | 30,000 (Pakistan) | --- | --- | 65.37 (91) | $ < 4 | |
Gamaleya c [19] | Sputnik V (Gam-COVID-Vac) (1011 vp rAd26-S, followed by 1011 vp rAd5-S 21 days apart) | 5476 | 16,501 | 62 | 16 | 91.6 | $ < 10 |
J&J (Janssen) d | Ad26.COV2.S (single dose 5 × 1010 vp) | 19,178 | 19,306 | 193 (34) | 66 (5) | 66 (85.4) | $2.80–9 |
Protein/VLP | |||||||
Novavax e | NVX-CoV2373 (2 × 5 μg + 50 μg M1 adjuvant, 21 days apart) | 15,000+ (UK) | 56 (1) | 6 (0) | 89.3 (UK) | $16 | |
Medicago f | CoVLP (2 × 3.75 μg + AS03 GSK adjuvant, 21 days apart) | 30,000 | ---- | --- | --- | Not known | |
Inactivated | |||||||
Sinovac g | CoronaVac (2× alum-adjuvanted 14 days apart) | 9200 (Brazil) | 167 (31) | 85 (7) | 50.4 (Brazil) | $30 | |
Sinopharm h (Beijing) | BBIBP-CorV (2 × 4 μg in alum adjuvant 21 days apart) | 10,000 (UAE) | ---- | --- | 79.3 (UAE) | $30–72.50 | |
Sinopharm i (Wuhan) | Vero (2 × 5 μg in alum adjuvant 21 days apart) | 27,000 (Peru, UAE, Bahrain, Morocco, Argentina, Jordan and Pakistan) | --- | --- | 72.5% | $30–72.50 | |
Bharat Biotech j | COVAXIN (BBV152) (2 × 6 μg in Alhydroxiquim-II adjuvant 28 days apart) | 25,800 | --- | --- | >50% | $2–3 |
2.1. Messenger RNA (mRNA) Vaccines
2.2. Viral Vector-Based (Non-Replicating) Vaccines
2.3. Recombinant Protein-Based Vaccines
2.4. Inactivated Virus
3. Clinical Trial Data of Twelve Vaccines Targeting COVID-19 in Phase III Trials and Emergency Use Authorization
3.1. mRNA Vaccines—Safety/Reactogenicity and Immunogenicity/Efficacy
Dose | N | Injection Site Pain | Headache | Fever | ||||
---|---|---|---|---|---|---|---|---|
Grade | Any | Any | Oral ≥ 38 °C | |||||
Group | Placebo + Vaccine | Placebo | Vaccine | Placebo | Vaccine | Placebo | Vaccine | |
mRNA | ||||||||
Pfizer/BioNTech BNT162b2 (2 × 30 μg, 21 d.a.) [16,43] | Post dose 1 | ~8183 a | 12% | 78% | 27% | 35% | 0.6% | 3% |
Post dose 2 | ~8183 a | 10% | 73% | 20% | 47% | 0% | 14% | |
Moderna mRNA-1273 (2 × 100 μg, 28 d.a.) [17,22,44] | Post dose 1 | ~30,300 b | 17.5% | 83.7% | 26.6% | 32.7% | 0.3% | 0.8% |
Post dose 2 | ~29,200 b | 17.0% | 88.2% | 23.4% | 58.6% | 0.3% | 15.5% | |
Viral Vector | ||||||||
Astra Zeneca AZD1222 (2 × 5 × 1010 vp, 28 d.a.) [18,25,26] | Post dose 1 | 964 c | 37% | 67% | 41% | 68% | 2% | 18% |
Post dose 2 | 128 d | --- | 30.7% | --- | % | --- | 0% | |
CanSino Ad5-nCoV (single dose 5 × 1010 vp) [28,29] | Post dose 1 | 255 e | 9% | 56% | 13% | 28% | 10% f | 16% f |
Post dose 2 | NA | NA | NA | NA | NA | NA | NA | |
Gamaleya Sputnik V (1011 vp Ad26 then 1011 Ad5 21 d.a.) [30] | Post dose 1 | 9 g | --- | 78% | --- | 67% | --- | 89% h |
Post dose 2 | 20 g | --- | 40% | --- | 55% | --- | 100% h | |
J&J (Janssen) (Ad26.COV2.S single 5 × 1010 vp) [21,49] | Post dose 1 | 673 j | 16.7% | 48.7% | 23.9% | 39.2% | 0.9% | 9.1% |
Post dose 2 | NA | NA | NA | NA | NA | NA | NA | |
Protein/VLP | ||||||||
Novavax NVX-CoV2373 (2 × 5 μg+ 50 μg M1, 21 d.a.) [34] | Post dose 1 | 49 k | 13% | 38% | 31% | 23% | 0% | 0% |
Post dose 2 | 49 k | 10% | 58% | 29% | 47% | 0% | 0% | |
Medicago CoVLP 2 × 3.75 μg+ AS03, 21 d.a. [35] | Post dose 1 | 20 m | --- | 95% | --- | 30% | --- | 0% |
Post dose 2 | 19 m | --- | 100% | --- | 57.9% | --- | 36.8% | |
Inactivated | ||||||||
Sinovac CoronaVac (2 × 3 µg + alum 14 d.a.) [36,37] | Post dose 1 | 180 p | 10% | 9.2% | 1.7% | 0.8% | 1.7% | 2.5% |
Post dose 2 | 180 p | 3.3% | 13.6% | 0% | 0.8% | 0% | 1.7% | |
Sinopharm BBIBP-CorV (2 × 4 μg vp + alum, 21 d.a.) [38] | Post dose 1 or 2 q | 112 | 4% | 12% | 7% | 1% | 4% | 4% |
Post dose 2 | --- | --- | --- | --- | --- | --- | --- | |
Sinopharm (Wuhan) Unnamed (2 × 5 μg vp + alum, 21 d.a.) [39] | Post dose 1 | 112 r | 14.3% | 6.0% | 0% | 0% | 3.6% | 1.2% |
Post dose 2 | 112 r | 10.7% | 9.5% | 0% | 0% | 0% | 1.2% | |
Bharat Biotech COVAXIN (2 × 6 μg Alhydroxiquim-II 28 d.a.) [42] | Post dose 1 | 175 s | --- | 3.2% | --- | 0.5% | --- | 4.2% |
Post dose 2 | 175 s | --- | 2.6% | --- | 1.5% | --- | 2.1% |
Timing | N | ELISA Titer | Virus Neutralization | γ-IFN+ CD4+ T Cells | Th1/Th2 CD4+ T cells | |||
---|---|---|---|---|---|---|---|---|
Units | dpd = Days Post Dose | GMT IgG | GMT = Geometric Mean Titer | %+ | Ratio of Measure | |||
Group | P + V | Placebo | Vaccine | Placebo | Vaccine | Vaccine | Vaccine | |
mRNA | ||||||||
Pfizer/BioNTech BNT162b2 (2 × 30 μg, 21 d.a.) [16,43] | 21 dpd 1 | ~30 a | 0.8 | 665.7 c | 10.0 | 13.0 d | --- | --- |
31 dpd 2 | 360 b | 0.8 | 4931.7 a,c | 10.0 | 316.1 d | 0.08% e | 4.4 f | |
Moderna mRNA-1273 (2 × 100 μg, 28 d.a.) [22,44] | 29 dpd 1 | ~180 g | 5.80 | 25.23 | 21.0 | 149.3 h | 0.02% j | >>1 j |
28 dpd 2 | ~180 g | 5.86 | 147.42 | 21.2 | 1095.8 h | 0.09% j | 28.5 j | |
Viral Vector | ||||||||
Astra Zeneca AZD1222 (2 × 5 × 1010 vp, 28 d.a.) [18,25,26,27] | 28 dpd 1 | 127 | 1 k | 546 k | 23.9 m, | 203.2 m | 0.06% p | 6.3 q |
28 dpd 2 | 112 | --- | 10,691 n | --- | 128 n | 0.097% n | --- | |
CanSino Ad5-nCoV (single dose 5 × 1010 vp) [28,29] | 28 dpd 1 | 255 | 20 r | 571 r | 4 s | 18.3 s | 0.01% t | --- |
NA | NA | NA | NA | NA | NA | NA | NA | |
Gamaleya Gam-COVID-Vac (1 × 1011 vp Ad26 then Ad5 21 d.a.a) [19,30] | 21 dpd 1 | 9 | 12.5 u | 1721 u | 1.25 v,w | 4.2 v | --- x | --- x |
21 dpd 2 | 456 | --- | 8996 u | 1.6 v | 44.5 v | --- | --- | |
J&J (Janssen) (Ad26.COV2.S single dose 5 × 1010 vp) [21,49] | 29 dpd 1 | ~314 | <50 | 399 y | <58 | 241 z | 0.09% α | 10 β |
NA | NA | NA | NA | NA | NA | NA | NA | |
Protein/VLP | ||||||||
Novavax NVX-CoV2373 (2 × 5 μg + 50 μg M1, 21 d.a.) [34] | 21 dpd 1 | ~52 | 110 δ | 1984 δ | 20 ε | 103 ε | --- | --- |
14 dpd 2 | ~50 | 114 δ | 63,160 δ | 20 ε | 3906 ε | 0.18% ζ | 7.5 ζ | |
Medicago CoVLP (2 × 3.75 μg + AS03, 21 d.a.) [35] | 21 dpd 1 | 20 | 64.8 w,η | 4354 η | 5 w,θ | 29.3 θ | 0.01% λ | 2.37 λ |
21 dpd 2 | 19 | --- | 295,240 η | --- | 811.3 θ | 0.06% λ | 1.4 λ | |
Inactivated | ||||||||
Sinovac CoronaVac (2 × 3 µg + alum, 14 d.a.) [36,37] | 14 dpd 2 | 176 ξ | 81 | 1094.3 | 2.0 | 27.6 | 0.00% π | --- |
28 dpd 2 | 176 ξ | 80 | 1053.7 | 2.0 | 23.8 | 0.07% π | --- | |
Sinopharm (Beijing) BBIBP-CorV 2 × 4 μg vp + alum, 21 d.a. [38] | 14 dpd 1 ς | 112 | --- | --- | 2 | 219 | --- | --- |
28 dpd 2 ς | 112 | --- | --- | 2 | 282 | --- | --- | |
Sinopharm (Wuhan) Unnamed 2 × 5 μg vp + alum, 21 d.a. [39] | 14 dpd 1 σ | 56 | --- | --- | --- | --- | --- | 0.92 φ |
14 dpd 2 σ | 56 | 10 | 215 | 5 | 247 | 1.21 φ | ||
Bharat Biotech COVAXIN (2 × 6 μg in Alhydroxiquim-II adjuvant, 28 d.a.) [40,41,42] | 28 dpd 1 ψ | 190 | 500 w | 2240 | 5.6 w | 12.8 | --- | --- |
28 dpd 2 ψ | 190 | --- | 9541 | --- | 160 | --- | 42 ω |
3.2. Viral Vector-Based (Non-Replicating) Vaccines—Safety/Reactogenicity and Immunogenicity/Efficacy
3.3. Protein-Based Vaccines—Safety/Reactogenicity and Immunogenicity/Efficacy
3.4. Inactivated Viral Vaccines—Safety/Reactogenicity and Efficacy/Immunogenicity
4. Comparative Analysis of Target Product Profiles
4.1. Safety/Reactogenicity—A SARS-CoV-2 Vaccine Should Provide a Clear Benefit/Risk Profile Based on 2+ Data Sets with at Least 10,000 Subjects across All Age Groups with the Dosing Regimen Intended for Licensure
4.2. Vaccine Efficacy—A SARS-CoV-2 Vaccine Should Demonstrate at Least 70% Efficacy, with Rapid Onset of Protection (<2 Weeks from Initial Dose), across All Age Groups, from Adolescents to Elderly with Appropriate Evaluation of Humoral and Cellular Immune Responses to Provide a Minimum Serological Correlate of Protection
4.3. Compliance (Relating to Dosing Regimen)—A Sars-Cov-2 Vaccine Should Be a Single Dose during an Outbreak (Optimal). A Two-Dose Regimen Is Acceptable Provided There Is a Short Interval (<28 Days) between Prime and Boost (Minimal)
4.4. Logistics (Product Stability/Storage/Supply Chain)—A SARS-CoV-2 Vaccine Should Have a Shelf Life of at Least 1 Year at −70 °C and Be Stable for at Least 1 Month at Fridge Temperature (4 °C)
4.5. COGS (Target Price/Accessibility)—A SARS CoV-2 Vaccine Should Possess Capability for Rapid Scale-Up Production and Availability of Sufficient Doses at Cost/Dose That Allows Broad Use, Including in LMIC
5. Discussion
5.1. Successes
5.2. Barriers/Hurdles
5.3. Limitations of This Analysis
5.4. Concluding Remarks
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Funk, C.D.; Laferrière, C.; Ardakani, A. Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective. Viruses 2021, 13, 418. https://doi.org/10.3390/v13030418
Funk CD, Laferrière C, Ardakani A. Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective. Viruses. 2021; 13(3):418. https://doi.org/10.3390/v13030418
Chicago/Turabian StyleFunk, Colin D., Craig Laferrière, and Ali Ardakani. 2021. "Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective" Viruses 13, no. 3: 418. https://doi.org/10.3390/v13030418
APA StyleFunk, C. D., Laferrière, C., & Ardakani, A. (2021). Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective. Viruses, 13(3), 418. https://doi.org/10.3390/v13030418