Challenge of COVID-19 vaccine discovery & development

BACKGROUND

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 protein^1,4-6.

Different SARS-CoV-2 lineages with diverse Spike protein mutant variants may yield a heavy impact on the course of the pandemic^2-3. 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 changes^7-8, 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).

Gene	Nucleotide	Amino acid
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)
	C23271A	A570D
	C23604A	P681H
	C23709T	T716I
	T24506G	S982A
	G24914C	D1118H
Orf8	C27972T	Q27stop
	G28048T	R52I
	A28111G	Y73C
N	28280 GAT->CTA	D3L
	C28977T	S235F

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.