The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine
Abstract
:1. Adenoviruses and Their Vectorization
1.1. Features of Adenoviruses
Species | Human Adenovirus Types | Tissue Tropism | Receptor (Ad Type) |
---|---|---|---|
A | 12, 18, 31, 61 | Intestine | CAR b (12) |
B | 3, 7, 16, 21, 50, 66, 89, 11, 14, 34, 35, 55, 68, 89, 106, 76–79 | Tonsils and respiratory tract, hematopoietic cells, kidney, urinary bladder | CD46 (3, 7, 11, 14, 16, 21, 34, 35, 50) DSG-2 c (3, 7, 11, 14, 55) HSPG, CD80/86 |
C | 1, 2, 5 a,f, 6, 57, 104, 108 | Respiratory tract Ad5 infect liver in mouse | CAR (1, 2, 5, 6), HSPG e MHC-I, VCAM-I, integrins |
D | 8–10, 13, 15, 17, 19, 20, 22, 23, 24, 25, 26 a, 27, 28, 29, 30, 32, 33, 36, 37, 38, 39, 42, 43–47, 48, 49, 51, 53, 54, 56, 58–60, 62–64, 65, 67, 69, 70, 71, 72, 73–75, 80, 81–88, 90–103, 105, 107, 109–113 | Eye, conjunctive tissues | CAR (9, 10) SA d (8, 19a, 37) CD46 (17, 26, 48, 49) |
E | 4 | Respiratory tract, eye | CAR |
F | 40, 41 | Intestine, enterocytes | CAR, HSPG |
G | 52 | Intestine | CAR, SA |
1.2. Adenoviral Vectors
2. Adenoviral Vectors Used in the COVID-19 Pandemic
2.1. Adenoviral Vectors Explored in the SARS-CoV2 Pandemic
2.2. Risks and Side Effects of the SARS-CoV2 Vaccine Vectors
3. Strategies to Improve the Adenovirus Vector Platform
3.1. Safety Challenges Faced by the Ad Vector Platform
3.2. Intelligent Engineering of the Adenovirus Vector Platform
3.3. Avoiding PF4 Binding and Subsequent Platelet Activation to Avoid VITT
3.4. Ad Vaccine Vectors Manufacturing and Administration Optimization
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Vector Type | Chimpanzee, ChAdY25 ChAdOx1 nCoV-19 (AZD1222) | Human Ad b Type 26 Ad26.COV2.S |
---|---|---|
Molecular setup | Deletion of E1 and E3 E4 ORF4, ORF6 and ORF6/7 replaced with Ad5 equivalent | E1 Deletion (bp 463-3364) E3 Deletion (bp 26,690-30,682) E4ORF6 replaced with Ad5 equivalent |
Clinical vaccination studies | Influenza A, Mycobacterium tuberculosis, MERS c -CoV, SARS-CoV1 | HIV d, Ebolavirus, Plasmodium, RSV e, HPV f, Filovirus |
Risks and side effects | Local reaction at puncture site, systemic (e.g., fever, muscle aches), VITT a | Local reaction at puncture site, systemic (e.g., fever, muscle aches), VITT a |
Dose and route of administration | 5 × 1010 vector particles intramuscular | 5 × 1010 vector particles intramuscular |
Administration schedule | Two doses at 4 to 12 weeks of interval | One dose |
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Sallard, E.; Zhang, W.; Aydin, M.; Schröer, K.; Ehrhardt, A. The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine. Viruses 2023, 15, 204. https://doi.org/10.3390/v15010204
Sallard E, Zhang W, Aydin M, Schröer K, Ehrhardt A. The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine. Viruses. 2023; 15(1):204. https://doi.org/10.3390/v15010204
Chicago/Turabian StyleSallard, Erwan, Wenli Zhang, Malik Aydin, Katrin Schröer, and Anja Ehrhardt. 2023. "The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine" Viruses 15, no. 1: 204. https://doi.org/10.3390/v15010204