Challenge of COVID-19 vaccine discovery & development
Challenge of COVID-19 vaccine discovery & development: to meet accumulated mutating of SARS-CoV-2 and a long-term viral genome transcrption
COVID-19 (Coronavirus Disease 2019) is novel viral pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also called 2019nCoV). The world is in midst of the COVID-19 pandemic. Effective vaccines are needed to halt the spread of the SARS-CoV-2 pandemic. Based on the data from WTO, there are 52 COVID-19 vaccines in clinical stage (Supplementary Table 1.) and 162 COVID-19 vaccine candidates in pre-clinical stage (Supplementary Table 2.) 2 mRNA vaccines, the BNT162b2 from Pfizer&BioNTech and the mRNA-1273 from Moderna, have recently been issued the emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA) for the prevention of COVID-19 in individuals 16 years of age and older.
The efficacy and safety of COVID-19 vaccine candidates need carefully investigated, from pre-clinical, clinal stage to a long time after BLA. There are 2 important items here:
Firstly, the coronavirus is kept accumulated mutating. The most important mutation occurs in SARS-CoV-2 (2019nCoV) Spike protein (SARS-CoV-2 S protein). The SARS-CoV-2 (2019nCoV) Spike mediates binding and entry into host cells and is a major target of neutralizing antibodies. Most of the COVID-19 vaccines focus on spike protein1,4-6.
Different SARS-CoV-2 lineages with diverse Spike protein mutant variants may yield a heavy impact on the course of the pandemic2-3. The United Kingdom (UK) has faced a rapid increase in COVID-19 cases caused by a novel SARS-COV-2 (2019nCOV) lineage, the B.1.1.7 lineage, which carries a larger than a usual number of coronavirus genetic changes7-8, particularly in the SARS-CoV-2 spike protein（Table 1）7.
Table 1 | All mutations and deletions occur in COVID-19 SARS-COV-2 (2019nCOV) B.1.1.7 lineage
(Click to more details about B.1.1.7 lineage related products).
|ORF1ab||C3267T||T1001I||C5388A||A1708D||T6954C||I2230T||11288-11296 deletion||SGF 3675-3677 deletion|
|spike||21765-21770 deletion||HV 69-70 deletion (Click to more details|
about HV 69-70 deletion related products)
|21991-21993 deletion||Y144 deletion||A23063T||N501Y (Click to more details |
about N501Y related products)
Secondly, SARS-CoV-2 was reported to integrate into the genome, which means a stable long-term expression of transcript products of SARS-CoV-2 9.
In conclusion, the Efficacy of COVID-19 vaccines and neutralized antibodies need long-term tracking, which mainly focuses on the novel spike protein mutation occurring in the new lineage variant of SARS-CoV2. The efficacy evaluation solution and tools of COVID-19 vaccines and neutralized antibodies need continually updated.
1. 2 Korber, B. et al. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. bioRxiv Preprint., doi:10.1101/2020.04.29.069054 (2020). 2. Investigation of novel SARS-COV-2 variant. Public health England. 3. European Centre for Disease Prevention and Control. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom – 20 December 2020.ECDC: Stockholm; 2020. 4. Li, G. & De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature Reviews Drug Discovery, doi:10.1038/d41573-020-00016-0 (2020). 5. Haque, A. & Pant, A. B. Efforts at COVID-19 Vaccine Development: Challenges and Successes. Vaccines 8, doi:10.3390/vaccines8040739 (2020). 6. Dong, Y. et al. A systematic review of SARS-CoV-2 vaccine candidates. Signal Transduction and Targeted Therapy 5, doi:10.1038/s41392-020-00352-y (2020). 7. Andrew Rambaut1, N. L., Oliver Pybus, Wendy Barclay, Jeff Barrett5, Alesandro Carabelli6, Tom Connor, Tom Peacock, David L Robertson8, Erik Volz, . Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. https://virological.org/ (2020). 8. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom. European Centre for Disease Prevention and Control: Publications & data. 9. Zhang, L. et al. SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome. bioRxiv Preprint. , doi:10.1101/2020.12.12.422516 (2020).