SARS-CoV-2 Spike P681H Antikörper (Alpha, Mu-Variante)

Since the first reported human infection with SARS-CoV-2 in December 2019, many  protein subunit  vaccines have been proposed for human use. Subunit vaccines Use one or more antigens suitable for eliciting a robust immune response. However, the main concern is the effectiveness of subunit vaccines and elicited antibodies to neutralize variants of SARS-CoV-2 such as B.1.1.7 (alpha), B.1.351 (beta) and P1 (gamma), B.1.617 ( Delta) and C.37 (Lambda). The spike protein (S) is a potential fragment for use as an antigen in vaccine development.

This protein plays a crucial role in the first step of the infection process as it binds to the ACE2 receptor (Angiotensin-Converting Enzyme 2) and after binding it enters the host cell. Immunization-induced specific antibodies against the receptor binding domain (RBD) can block and effectively prevent viral invasion. The focus of this review is the impact of spike mutant variants of SARS-CoV2 (alpha, beta, gamma, delta and lambda) on the efficacy of subunit recombinant vaccines . Little or no significant impact on vaccine efficacy against alpha and delta variants has been reported to date. Such an impact on vaccine efficacy for beta, delta, gamma and lambda variants may be even greater compared to the alpha variant. Still, more comprehensive analyzes are needed to assess the true impact of the SARS-CoV-2 variants on vaccine efficacy.

introduction

The routine status of life in the world has been halted by the  severe acute respiratory syndrome coronavirus 2  (SARS-CoV-2) pandemic. It causes significant health, social and economic burdens worldwide.  SARS-CoV-2 is a positive-sense, single-stranded RNA virus that evolves rapidly and continuously accumulates genomic mutations as it continues to be transmitted.  Since the first reported human infection with SARS-CoV-2 in Wuhan in December 2019  many protein subunit  vaccines  have been presented  for human use. Nevertheless, viral genome mutations leading to new variants are a real challenge in the global fight against this pandemic.   A major focus of this review is to evaluate the impact of spike mutant variants of SARS-CoV2 (B.1.1.7, B.1.351 and B.1.1.28.1) on the efficacy of  recombinant subunit vaccines  that have been developed to elicit an immune response against the spike protein of SARS-CoV2.

methods

Independent searches of PubMed,  Web of Science  and Global  Index Medicus  were conducted by two researchers in June 2021. The search strategy consisted of a word combination covering the following areas (Covid-19 OR SARS-CoV-2) AND vaccine AND B.1.1.7 variant OR B.1.351 variant OR B.1.1.28.1 variant OR B.1.617.2 OR C.37 variant. The search had no geographic or language limitations and included all studies reporting the efficacy of SARS-CoV-2 vaccines against alpha, beta, gamma, delta and lambda variants. Here we narratively describe the most important results of the included studies.

The genomic features of SARS-CoV-2

The SARS-CoV-2 is a spherical virion containing a positive-strand RNA virus with a genome length of approximately 29,700  nucleotides  .  The 5ˊ end spans more than two-thirds of the genome and includes a long ORF1ab  polyprotein  that encodes 16 nonstructural proteins.  The 3ˊ end encodes four major structural proteins, namely the spike (S) protein,  nucleocapsid  (N) protein, membrane (M) protein and coat protein (E).   In addition, the virus contains six accessory proteins encoded by the genes ORF3a, ORF6, ORF7a, ORF7b, ORF8 and ORF9b.  ORF3a is a Transmembrane protein that forms ion channels in the host membrane and encodes ORF7a, a type I transmembrane protein(10). ORF8 is a protein with an N-terminal  signal sequence  for  endoplasmic reticulum transport  and ORF9b represses the IFN-I response(9).

Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein

S protein  , a  glycoprotein  , is a  homotrimer that   plays a crucial role in the first step of infection.   The  monomer  of S protein contains 1273 amino acids and has a molecular weight of approximately 140 kDa.  The primary function of S protein is to bind to the ACE2 (angiotensin-converting enzyme 2) receptor, which after binding enters the host cell.  ACE2  is a type I integral membrane protein that functions as a carboxypeptidase and  angiotensin Cleaves II to blood pressure regulating angiotensin.

  • The virus binds to ACE2 on the host cell (lung, heart, etc.) for viral entry and subsequent pathogenesis, resulting in severe respiratory infection. Therefore, the S protein-ACE2 interaction is an easy target for vaccines.  First, it is exposed on the surface and can be directly recognized by the host’s immune system. 
  • Second, it mediates the interaction with the host cell’s binding to the ACE2 receptor, which is essential for the subsequent entry of the virus into the target cells, causing subsequent  pathogenicity  . fifteen   Finally, the homologous proteins have already been used for vaccine development against SARS-CoV and MERS-CoV and have been shown to be effective.
  • The S protein consists of two functional subunits, including an N-terminal S1 subunit (Val16–Gln690). It consists of S1A, S1B, S1C and S1D domains. The latter is responsible for binding to the host cell  receptor  .
  • A C-terminal membrane-proximal S2 subunit contains the essential elements and is responsible for the fusion of the viral and cellular membranes. This subunit consists of four parts, including an internal  membrane fusion  peptide (FP), two 7-peptide repeats, a membrane-proximal external region, and a  transmembrane domain  (TM). 
  • The S1A domain, called the N-terminal domain (NTD), recognizes carbohydrates such as  sialic acid  , which is required for the virus to attach to the host cell surface.  The S1B domain (Arg319–Phe541), termed the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, interacts with the human ACE2 receptor. The S1 subunit can be further defined into two domains referred to as the N-terminal domain (NTD) and the C-terminal domain (CTD). The River Basin District is in the CTD. The structural parts within the S2 subunit include three long α-helices, several α-helical segments, extensive twisted β-sheets, a membrane-spanning α-helix, and an intracellular cysteine-rich segment.  Located between the S1 and S2 subunits in SARS-CoV-2, the PRRA  sequence motif  features a furin cleavage site. In the S2 subunit there is a second proteolytic cleavage site S20, upstream of the fusion peptide. These two interfaces are involved in viral entry into host cells

The S protein is a potential fragment to be used as antigen in vaccine designing including various forms of the full-length S protein, RBD domain, S1 subunit, NTD, and FP.  The RBD of S protein interacts with the ACE2 receptor on host cells directly. The RBD immunization-induced specific antibodies may block this recognition and effectively prevent the viral invasion.  Most SARS-CoV-2  subunit vaccines  currently under development use RBD as the antigen. Moreover, the RBD domain was also used to develop SARS-CoV and MERS-CoV vaccines. 

The S protein is a potential fragment to be used as antigen in vaccine designing including various forms of the full-length S protein, RBD domain, S1 subunit, NTD, and FP.  The RBD of S protein interacts with the ACE2 receptor on host cells directly. The RBD immunization-induced specific antibodies may block this recognition and effectively prevent the viral invasion.  Most SARS-CoV-2  subunit vaccines  currently under development use RBD as the antigen.  Moreover, the RBD domain was also used to develop SARS-CoV and MERS-CoV vaccines. 

Subunit vaccines against SARS-CoV-2

Subunit vaccines use one or more antigens suitable for eliciting a robust immune response. In theory, the subunit vaccine is very easy and safe, but in practice, it requires a suitable adjuvant to stimulate the host immune response. Several previous attempts were partially successful with SARS-CoV. Immunization of animals with the S1 RBD domain fused with the IgG1 FC portion (RBD-FC) induced highly potent antibodies, which could bind with the RBD domain of the S1 domain, completely neutralized SARS-CoV, and inhibited SARS-CoV entry into Vero E6 cells.

SARS-CoV-2 Spike P681H Antibody (Alpha, Mu Variant)

9359-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 Spike P681H Antibody (Alpha, Mu Variant)

9359-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 Spike P681H Antibody [9F7E4] (Alpha, Mu Variant)

PM-9371-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 Spike P681H Antibody [9F7E4] (Alpha, Mu Variant)

PM-9371-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 Spike P681H Antibody [1G8D11] (Alpha, Mu Variant)

PM-9373-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 Spike P681H Antibody [1G8D11] (Alpha, Mu Variant)

PM-9373-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 Spike P681H Antibody [7A4D12](Alpha, Mu Variant)

PM-9374-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 Spike P681H Antibody [7A4D12](Alpha, Mu Variant)

PM-9374-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 Spike P681H Antibody [7C11H11] (Omicron, Alpha Variant)

PM-9375-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 Spike P681H Antibody [7C11H11] (Omicron, Alpha Variant)

PM-9375-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Alpha Variant (B.1.1.7, UK) Spike P681H Peptide

9359P ProSci 0.05 mg 235.5 EUR

Recombinant SARS-CoV-2 Spike Glycoprotein(S) (D614G), Partial

E80028 EpiGentek
  • 388.30 EUR
  • 860.20 EUR
  • 20 ul
  • 100 ul

SARS-CoV-2 Spike P26S Antibody (Gamma Variant)

9573-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 Spike P26S Antibody (Gamma Variant)

9573-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 Spike S1 RBD Protein, Avi-His-tag

E80024 EpiGentek
  • 635.80 EUR
  • 4995.10 EUR
  • 100 ul
  • 1 ml

SARS-CoV-2 Spike S1 RBD Protein, Mouse Fc-fusion

E80026 EpiGentek
  • 588.50 EUR
  • 823.90 EUR
  • 20 ul
  • 50 ul

SARS-CoV-2 Spike P26S Peptide (Gamma Variant)

9573P ProSci 0.05 mg 235.5 EUR

SARS-CoV-2 (COVID-19) Mu Variant (B.1.621) Spike RBD (R346K, E484K, N501Y, D614G, P681H) Recombinant Protein

21-830 ProSci 0.1 mg 714.3 EUR

SARS-CoV-2 Spike S1 (16-685) Protein, Avi-His-tag

E80021 EpiGentek
  • 635.80 EUR
  • 4276.80 EUR
  • 100 ul
  • 1 ml

SARS-CoV-2 Spike S1 RBD (V367F) Protein, Avi-His-tag

E80023 EpiGentek
  • 635.80 EUR
  • 3934.70 EUR
  • 100 ul
  • 1 ml

SARS-CoV-2 Spike S1 (13-665) Protein, Fc Fusion, Avi-tag

E80020 EpiGentek
  • 635.80 EUR
  • 4276.80 EUR
  • 100 ul
  • 1 ml

SARS-CoV-2 Spike S1 (16-685) Protein, Fc Fusion, Avi-tag

E80022 EpiGentek
  • 635.80 EUR
  • 4276.80 EUR
  • 100 ul
  • 1 ml

SARS-CoV-2 Spike S1 RBD Protein, Human Fc-Fusion, Avi-Tag

E80025 EpiGentek
  • 635.80 EUR
  • 3934.70 EUR
  • 100 ul
  • 1 ml

SARS-CoV Spike Antibody

3219-002mg ProSci 0.02 mg 206.18 EUR

SARS-CoV Spike Antibody

3219-01mg ProSci 0.1 mg 523.7 EUR

SARS-CoV Spike Antibody

3221-002mg ProSci 0.02 mg 206.18 EUR

SARS-CoV Spike Antibody

3221-01mg ProSci 0.1 mg 523.7 EUR

SARS-CoV Spike Antibody

3223-002mg ProSci 0.02 mg 206.18 EUR

SARS-CoV Spike Antibody

3223-01mg ProSci 0.1 mg 523.7 EUR

SARS-CoV Spike Antibody

3225-002mg ProSci 0.02 mg 206.18 EUR

SARS-CoV Spike Antibody

3225-01mg ProSci 0.1 mg 523.7 EUR

SARS-CoV-2 (COVID-19) Spike L452R Antibody (Delta Variant)

9463-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike L452R Antibody (Delta Variant)

9463-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 Spike Peptide

9083P ProSci 0.05 mg 235.5 EUR

SARS-CoV-2 Spike Peptide

9087P ProSci 0.05 mg 235.5 EUR

SARS-CoV-2 Spike Peptide

9091P ProSci 0.05 mg 235.5 EUR

SARS-CoV-2 Spike Peptide

9095P ProSci 0.05 mg 235.5 EUR

Recombinant SARS-CoV-2 Spike Glycoprotein(S) (D614G), Partial

E80028-2 EpiGentek 100 ul 860.2 EUR

SARS-CoV-2 Spike Monoclonal Antibody

A73664-050 EpiGentek 50 ul 341 EUR

SARS-CoV-2 Spike Monoclonal Antibody

A73664-100 EpiGentek 100 ul 518.1 EUR

SARS-CoV-2 Spike Monoclonal Antibody

A73664 EpiGentek
  • 341.00 EUR
  • 518.10 EUR
  • 50 ul
  • 100 ul

SARS-CoV-2 (COVID-19) Spike P681R Peptide (Delta Variant)

9673P ProSci 0.05 mg 235.5 EUR

SARS-CoV Spike Protein

abx060655-1mg Abbexa 1 mg 2030.4 EUR

SARS-CoV-2 (COVID-19) Spike 156-157EFdel Antibody (Delta Variant)

9689-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike 156-157EFdel Antibody (Delta Variant)

9689-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike P26S Antibody [5G12G11] (Gamma Variant)

PM-9590-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike P26S Antibody [5G12G11] (Gamma Variant)

PM-9590-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike P681R Antibody [5H4C5] (Delta Variant)

PM-9677-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike P681R Antibody [5H4C5] (Delta Variant)

PM-9677-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike P681R Antibody [7E3C5] (Delta Variant)

PM-9680-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike P681R Antibody [7E3C5] (Delta Variant)

PM-9680-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV spike protein Antibody

abx023139-100ug Abbexa 100 ug 1028.4 EUR

SARS-CoV spike protein Antibody

abx023143-100ug Abbexa 100 ug 1028.4 EUR

SARS-CoV-2 Spike S1 RBD Protein, Avi-His-tag

E80024-2 EpiGentek 1 ml 4995.1 EUR

SARS-CoV-2 Spike S1 RBD Protein, Mouse Fc-fusion

E80026-2 EpiGentek 50 ul 823.9 EUR

SARS-CoV-2 Spike S2 Peptide

9119P ProSci 0.05 mg 235.5 EUR

SARS-CoV-2 Spike S2 Peptide

9123P ProSci 0.05 mg 235.5 EUR

SARS-CoV-2 Spike RBD Nanobody

A73680-050 EpiGentek 50 ul Ask for price

SARS-CoV-2 Spike RBD Nanobody

A73680-100 EpiGentek 100 ul 882.2 EUR

SARS-CoV-2 Spike RBD Nanobody

A73680 EpiGentek
  • Ask for price
  • 882.20 EUR
  • 50 ul
  • 100 ul

SARS-CoV-2 (COVID-19) Spike Antibody

3525-002mg ProSci 0.02 mg 206.18 EUR

SARS-CoV-2 (COVID-19) Spike Antibody

3525-01mg ProSci 0.1 mg 523.7 EUR

Anti-SARS-CoV-2 Spike S1 Antibody

A3000-50 Biovision 50 µg 502.8 EUR

SARS-CoV-2 Nucleocapsid Protein, Avi-His-tag

E80027 EpiGentek
  • 635.80 EUR
  • 4087.60 EUR
  • 1 ml
  • 100 ul

SARS-CoV-2 Spike S1 (16-685) Protein, Avi-His-tag

E80021-2 EpiGentek 1 ml 4276.8 EUR

SARS-CoV-2 Spike S1 RBD (V367F) Protein, Avi-His-tag

E80023-2 EpiGentek 1 ml 3934.7 EUR

SARS-CoV-2 (COVID-19) Alpha Variant (B.1.1.7, UK) Spike RBD Recombinant Protein

21-824 ProSci 0.1 mg 1186.8 EUR

SARS-CoV-2 (COVID-19) Variant Spike Protein RBD (E484D) Recombinant Protein

21-829 ProSci 0.1 mg 714.3 EUR

SARS-CoV-2 Spike S1 (13-665) Protein, Fc Fusion, Avi-tag

E80020-2 EpiGentek 1 ml 4276.8 EUR

SARS-CoV-2 Spike S1 (16-685) Protein, Fc Fusion, Avi-tag

E80022-2 EpiGentek 1 ml 4276.8 EUR

SARS-CoV-2 Spike S1 RBD Protein, Human Fc-Fusion, Avi-Tag

E80025-2 EpiGentek 1 ml 3934.7 EUR

SARS-CoV-2 (COVID-19) Spike S1 Antibody

9083-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike S1 Antibody

9083-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike RBD Antibody

9087-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike RBD Antibody

9087-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike 681P Antibody

9091-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike 681P Antibody

9091-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike S2 Antibody

9119-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike S2 Antibody

9119-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike S2 Antibody

9123-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike S2 Antibody

9123-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike Antibody (biotin)

3525-biotin-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike Antibody (biotin)

3525-biotin-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Spike Antibody (HRP)

3525-HRP-002mg ProSci 0.02 mg 229.7 EUR

SARS-CoV-2 (COVID-19) Spike Antibody (HRP)

3525-HRP-01mg ProSci 0.1 mg 594.26 EUR

SARS-CoV-2 (COVID-19) Alpha Variant (B.1.1.7, UK) Spike S1 (RBD) Recombinant Protein

21-808 ProSci 50 ug 619.8 EUR

SARS-CoV-2 (COVID-19) Alpha Variant (B.1.1.7, UK) Spike S1 (RBD) Recombinant Protein

21-811 ProSci 50 ug 537.9 EUR

SARS-CoV-2 (COVID-19) Full-Length Alpha Variant (B.1.1.7, UK) Spike Recombinant Protein

21-818 ProSci 0.025 mg 796.2 EUR

SARS-CoV-2 (COVID-19) Omicron Variant (B.1.1.529) Spike RBD Recombinant Protein

21-844 ProSci 0.1 mg 714.3 EUR

SARS-CoV-2 (COVID-19) Omicron Variant (B.1.1.529) Spike Trimer Recombinant Protein

21-845 ProSci 0.1 mg 714.3 EUR

SARS-CoV-2 (COVID-19) Gamma Variant (P.1, Brazil) Spike S1 (RBD) Variant Recombinant Protein

21-810 ProSci 50 ug 619.8 EUR

SARS-CoV-2 (COVID-19) Gamma Variant (P.1, Brazil) Spike S1 (RBD) Variant Recombinant Protein

21-813 ProSci 50 ug 537.9 EUR

Sars-Cov, Spike (Middle) Recom Protein

abx060656-1mg Abbexa 1 mg 2030.4 EUR

SARS-CoV-2 (COVID-19) Spike Recombinant Protein

20-233 ProSci 0.1 mg 726.9 EUR

SARS-CoV-2 (COVID-19) Spike Recombinant Protein

11-073 ProSci 0.1 mg 695.4 EUR

SARS-CoV-2(COVID-19) Spike Recombinant Protein

10-411 ProSci 0.1 mg 714.3 EUR

Recombinant Coronavirus Spike Protein (SARS-CoV-2; ECD)

P1533-10 Biovision 10 µg 235.2 EUR

Recombinant Coronavirus Spike Protein (SARS-CoV-2; ECD)

P1533-50 Biovision 50 µg 709.2 EUR

SARS-CoV-2 (COVID-19) Spike Matched Pair

MPS-0001 ProSci 1 Set 1029.3 EUR

SARS-CoV-2 (COVID-19) Spike Matched Pair

MPS-0002 ProSci 1 Set 1029.3 EUR

So far, several companies and academics have started plans on the SARS-CoV-2 subunit vaccine . Almost all of them use the S protein as an antigenic target. For example, Novavax, Inc. announced to have produced multiple nanoparticle vaccine candidates based on S protein. Besides, the Pasteur Institute of Iran and Finley institute of Cuba also prepared subunit vaccines against SARS-CoV-2. To facilitate the development of a SARS-CoV-2 vaccine, the preferred adjuvant varied widely, including the classic aluminum adjuvant that enhances the immune response by facilitating phagocytosis and slowing the diffusion of antigens from the injection site. It can efficiently stimulate the Th2 immune response upon injection. The F59, MF59 have already been used in flu vaccines in Europe and the United States. The mechanism of MF59 is to recruit immune cells to induce antigen-specific immune responses. The adjuvant system (AS) comprises a series of adjuvants improved by GlaxoSmithKline (GSK), including AS01, AS02,  AS03 , and  AS04  Among them, AS01 is a  liposome  adjuvant.

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