A novel infectious disease COVID-19 pandemic caused due to severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2), first emerged in late 2019 in Wuhan, China. Novel corona virus is member of beta-coronavirus family, having high human to human transmission than SARS-CoV and MERS-CoV. The transmission of COVID-19 occurs through respiratory droplets generated by coughing and sneezing. There is no specific treatment or vaccine registered for disease. The various antigen selected as M protein, E protein, S protein, RBD and N protein etc. The various types of vaccine are in pipeline among them some are succeed in preclinical trials and further it is in phase -1 trials. The various research institute and companies working on it, so the chances of getting the first corona vaccine is increased and race between various companies are seen in present. According to Nature review presently 90 Vaccine development studies against COVID-19 are going on in an entire globe.
A novel corona disease is caused by severe acute respiratory Syndrome SARS- CoV-2, belongs to betacoronavirus family. On February 11, WHO named the virus SARS-CoV-2 and syndrome as COVID-19. First emerged in Wuhan, China in late 2019. Novel corona virus has high human to human transmission than SARS-CoV and MERS-CoV. The infection is seen to be high in patients who are above 60 yrs old and those who have previous chronic medical history such as diabetes and hypertension (1). The transmission of COVID-19 occur through respiratory droplets generated by coughing and sneezing. It is positive strand RNA virus, the genome of virus is approximately 29700 base pair long sequence. At 5’ end it has ORF1ab, which encodes 13-15 non structural proteins and at 3’end genome encodes 4 proteins viz. Spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein. At cellular level SARS-CoV-2 S protein (RBD protein) binds to human ACE -2 receptors leads to entry and subsequent pathogenesis. Resulting in various symptoms like fever, sore throat, cough and shortening of breath (2). As per worldometer SARS-CoV-2 spread in globe around 204 countries. Total no of patients are 4422930 among them 1659806 are recovered while 298170 patients are death and the numbers increasing day by day (3).
Vaccines are most effective to prevent and control infectious disease. There is no specific treatment and vaccine available against COVID-19. The development of vaccine against COVID-19 is urgently required. Various Research institute and companies working on vaccine development against COVID-19. According to Nature in the globe 90 studies are going on to vaccine development against COVID-19. I summarized various current studies of vaccine development against covid-19 (2).
Various targets ( Antigen selection)
Various antigen selected for vaccine development against COVID-19 viz. whole cell antigen, S protein, M protein, N protein, E protein, receptor binding domain (RBD) and N-terminal domain (NTD).
Whole cell antigen
The whole cell consist of all cell necessary elements such as protein, lipids, polysaccharide, and some other components. Whole cell antigen is mainly used for developing whole cell killed and live attenuated vaccine. SARS- CoV-2 strains are isolated by some Institute and working on development of live attenuated vaccine. The stringent requirement of this type of vaccine is isolated strain should be with low pathogenicity (2).
Spike protein ( S protein)
Spike protein is surface protein of SARS-CoV-2 and it is directly recognised by host immune system. It is most promising antigen formulation for SARS-CoV -2 vaccine (2). It mediates interaction with ACE-2 of human cell, leads to pathogen entry and subsequent infection. The homologous protein were already used for MERS-CoV and SARS -CoV. Consist two domain C-terminal domain and N- terminal domain. Receptor binding domain (RBD) present at C-terminal domain. The monomer of SARS-CoV-2 contains 1273 amino acids with molecular weight 140kDa. Clover biopharmaceuticals started working on SARS-CoV -2 S protein trimmer vaccine (4, 5).
Receptor binding domain (RBD)
Since RBD of S protein directly interacts with the ACE2 receptors on host cells, RBD immunization induced specific antibodies may block the recognition and thus effectively prevent the invasion of the virus (6).
Nucleocapsid protein ( N protein)
N protein is most abundant and highly conserved protein in coronavirus. It mainly involved in formation of nucleocapsid, RNA replication, mRNA transcription and signal transduction. Vaccine against SARS-CoV N protein gives strong humoral and cellular immunity (4).
Various types Of vaccine under development against covid-19
Whole cell killed and live attenuated vaccine
Whole-cell killed or live-attenuated vaccines contains multiple antigenic components to the host, which can potentially induce diverse immunologic effectors against pathogen. Currently, various research institutions working on this type of vaccine like, The Chinese Centers for Disease Control and Prevention, Wuhan Institute of Virology, Chinese Academy of Sciences, Zhejiang University, and several other institutions have successfully isolated the virus strains of SARS-CoV-2 and started relevant vaccine development. Besides, Codagenix, Inc. announced the collaboration with the Serum Institute of India, Ltd. to develop a live-attenuated vaccine against SARS-CoV-2. They use viral deoptimization to synthesize “rationally designed” live-attenuated vaccines. This technology starting with the sequence of the viral genome and allows for the rapid generation of multiple vaccine candidates against the virus. Major advantage of whole virus vaccines is their inherent immunogenicity and ability to stimulate toll-like receptors (TLRs) including TLR 3, TLR 7/8, and TLR 9. However, live virus vaccines often require extensive additional testing to confirm their safety ( 4, 5, 7).
Subunit vaccines include one or more antigens with strong immunogenicity capable of efficiently stimulating the host immune system. In general, this type of vaccine is safer and easier to produce, but often requires the addition of adjuvants to elicit a strong protective immune response. University of Queensland is synthesizing viral surface proteins, to present them more easily to the immune system. Moreover, Novavax has developed and produced immunogenic virus-like nanoparticles based on recombinant expression of the S-protein. Accordingly, a consortium led by Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine (including University of Texas Medical Branch and New York Blood center) has developed and tested a subunit vaccine comprised of only the receptor-binding domain (RBD) of the SARS-CoV S-protein (2, 5, 7).
With the development and maturing of mRNA synthesis, modification, and delivery technology, the research on mRNA vaccine has regained attention during the last two decades. mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, short production cycles, low-cost manufacturing, and safe administration. Fudan University is in collaboration with Shanghai Jiaotong University and Bluebird Biopharmaceutical Company to develop a SARS-CoV-2 mRNA vaccine using two different strategies. The first is to use mRNA to express the SARS-CoV-2 S protein and RBD domain, the efficacy of this vaccine is now under evaluation in mice. The second is the use of mRNA to express virus-like particles in vivo. In addition, German biopharmaceutical company CureVac AG, Stermirna Therapeutics, BDGENE Therapeutics, Guanhao Biotech, ZY Therapeutics Inc., CanSino Biologics Inc., Baylor College of Medicine, University of Texas, Tongji university also announced their progress on mRNA vaccine development against SARS-CoV-2 (2, 4, 7).
DNA vaccines are typically comprised of plasmid DNA molecules that encode one or more antigens. They are superior to mRNA vaccines in the formulations needed for stability and delivery efficiency, nevertheless they need to enter the nucleus that may bring in the risk of vector integration and mutations in the host genome. Inovio Pharmaceuticals developed a DNA vaccine candidate termed INO-4800, which is in preclinical studies and will soon enter phase I clinical trials. Applied DNA Sciences Subsidiary, LineaRx, and Takis Biotech collaborated for the development of a linear DNA vaccine candidate against SARS-CoV-2, which is now in preclinical studies. (2, 4, 7).
Live vector vaccine
Vector vaccines are live viruses (the vector) that express a heterologous antigen(s). They are characterized by combining the strong immunogenicity of live attenuated vaccines and the safety of subunit vaccines, and were widely used to induce cellular immunity in vivo. Related SARS-CoV-2 vaccine research has been carried out by the following institutions. Houston-based Greffex Inc. has completed the construction of SARS-CoV-2 adenovirus vector vaccine with Greffex Vector Platform and should have now moved to animal testing. Tonix Pharmaceuticals announced research to develop a potential SARS-CoV-2 vaccine based on Horsepox Virus (TNX-1800). Johnson & Johnson has adopted the AdVac® adenoviral vector platform for vaccine development (2, 4, 7).
Vaccines contain only certain fragments of intact antigens and are usually prepared by chemical synthesis techniques. They are easier in preparation and quality control. However, the low molecular weight and structural complexity of these vaccines usually result in low immunogenicity, thus structural modifications, delivery systems, and adjuvants are additionally required in the formulation. Generex Biotechnology was announced they were working with third-party groups to generate peptide vaccines against pandemic viruses using the patented NuGenerex Immuno-Oncology Ii-Key technology that uses synthetic peptides in mimic essential protein regions from a virus that is chemically linked to the 4-amino acid Ii-Key to ensure robust immune system activation (2, 4, 7).
Presently we know very little about SARS-CoV-2. There are numerous questions than answers for the newly identified virus, including the etiology, epidemiology, structural basis, mechanism of pathogenesis, pathological immune response, etc. Recently, more and more countries and R&D institutions announced their program on vaccine development against SARS-CoV-2. However, vaccine development has its own rules, and a successful SARS-CoV-2 vaccine could not be achieved overnight. After vaccine design and preparation, it will undergo efficacy and safety evaluation, quality standard establishment before entering clinical trials. Generally, three phases of clinical trials will be carried out to evaluate the safety, immunogenicity, and efficacy of the vaccine. Currently, clinical trials testing different drugs are ongoing and will possibly allow the identification of a potential drug to treat the disease associated to SARS-CoV-2, and the rapid development and application of a vaccine is a powerful means to prevent the global epidemic of COVID-19. Currently some are in clinical trials they will get success and entire globe have the vaccine against COVID-19. Which help in preventing and spreading of SARS-CoV-2 (2, 7).
By understanding and summarising various current studies of vaccine development against covid-19, I will conclude that researchers and various companies working on vaccines and some of them succeed in preclinical trials and some are in clinical trials. The numerous types of vaccine developments are going on against COVID-19. There are 90 vaccine studies going on presently. So the chances of getting 1st COVID-19 vaccine are very much.
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- Amanat Fatima and Florian Krammer. SARS-CoV-2 vaccines: status report. Immunity (2020), doi 10.1007/s40475-020-00201-6
- Tai Wanbo et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular & molecular immunology 1-8 (2020), doi.org/10.1038/s41423-020-0400-4.
- World Health Organization. DRAFT landscape of COVID-19 candidate vaccines. World Health Organization. https://www. who. int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov. pdf (2020), accessed on 12/5/2020
- Thanh Le T, Andreadakis Z. et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov 10 (2020), doi: 10.1038/d41573-020-00073-5.