Multiple platforms are under development. Among those with the greatest potential for speed are DNA- and RNA-based platforms, followed by those for developing recombinant-subunit vaccines. RNA and DNA vaccines can be made quickly because they require no culture or fermentation, instead using synthetic processes.

The need to rapidly develop a vaccine against SARS-COV-2 comes at a time of the explosion in 

Basic scientific understanding including in areas of genomics and molecular biology, that is supporting a new future of vaccine development. 

The coalition for epidermic preparedness innovation (CEPI) is working with global health authorities to develop a vaccine against COVID-19. In this blog, we will see the key characteristics of the COVID-19 vaccine and R&D. 

COVID-19 vaccine and R&D insight

The global COVID-19 vaccine R&D includes 115 vaccine candidates, of which 78 are confirmed as active and 37 are unconfirmed. And in that 78 the most advanced candidates moved into clinical development include mRNA-1273, Ad5-nCoV, INO-4800, LV-DMENP-DC, and pathogen specific aAPC.

Diversity of technology platform

In this vaccine development against COVID-19 technology platform being evaluated, including the     

  • nucleic acid (DNA and RNA)      
  • peptide
  • virus like particle
  • viral vector (replicating and non-replicating)
  • recombinant protein          
  • live attenuated virus 
  • inactivated virus approaches               

and it is possible that some vaccine platforms may be better suited to specific subtypes such as elderly, children, pregnant women, immunocompromised patients.                                                                                             

  • The vaccine based on DNA and mRNA is showing good results based on the antigen manipulation property. Scientists start working on vaccine mRNA-1273 just after few months of sequence identification of COVID-19. 
  • A vaccine based on viral vector shows high protein expression and long term stability and gives a strong immune response.
  • And some use adjuvants (an agent that improves the immune response to produce more antibodies and long-lasting immunity) can enhance immunogenicity and make lower doses affected. 

How basically vaccine work 

Basically, vaccine affect the virus replication by following two ways:

  • Most vaccines aim to induce neutralizing antibodies against viral spike (S) protein
  • Preventing uptake of coronavirus by the cell via ACE2 receptor.
Fig. 1 Pipeline of COVID-19 vaccine candidates by technology platform.
Fig. 1 Pipeline of COVID-19 vaccine candidates by technology platform.

Investigated projects split into confirmed or unconfirmed are in the early planning stage with no testing and preclinical stage in which testing occurs.

Of the confirmed vaccine candidates, maximum done by private developers, and not by governmental agencies, we need to ensure coordination of vaccine manufacturing and supply capability and capacity to meet demand.

In order to assess vaccine efficacy, COVID-19 specific animal models are being developed, including ACE2-transgenic mice, hamsters, ferrets, and non-human primates.

Figure 2 : clinical phase vaccine candidates for COVID-19
Figure 2 : Clinical phase vaccine candidates for COVID-19

Current status of vaccine

1. mRNA-1273

The company has already successfully completed phase 1 trials of its vaccine candidate. It was given the go-ahead by the FDA to begin the phase 2 trial and is all set to conduct it on 600 healthy individuals. The vaccine is being developed in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) in the US. The vaccine candidate was also granted a ‘fast track’ designation by the FDA and the company is slated to begin phase 3 trials in the month of July, whose results may be available by the end of 2020.

How it’s work

  • The RNA-based vaccine work by carrying the molecular instruction to make protein which is known as mRNA sequence. 
  • So mRNA-1273 carries the mRNA strand of the spike protein of novel coronavirus, which uses by human cells to produced antigen required to fight the virus.

Advantages

  1. Rapid manufacturing rate 
  2. Safer than using a weakened virus for getting an immune response

2. Ad5-nCOV

CanSino Bio’s Ad5-nCoV is the most advanced DNA vaccine candidate at the moment against COVID-19. The candidate completed the Phase 1 trial and the company apparently enrolling patients for a Phase II trial. The Chinese vaccine has been named as a top contender by the World Health Organization.

Adenoviruses are a group of viruses that causes infection in the eyes, trachea, lungs, and nervous system. And the vector means a virus or agent that is used to deliver DNA to a cell.

How it’s work

  • The vaccine uses adenovirus to deliver the DNA coronavirus protein.
  • The vaccine is a hybrid of “live virus” and “recombinant protein” being used to generate spike protein antigens to trigger an immune response.

3. INO-4800 DNA vaccine

INO-4800 is a DNA vaccine candidate matched to the novel coronavirus SARS-COV-2, which causes the COVID-19 disease in humans. Inovio’s has a smart device called CELLECTRA (use electric pulses) it is the future for activation immunotherapy.

The German manufacturer company is support large-scale manufacturing of INOVIO’s investigational DNA vaccine INO-4800, which currently is in Phase 1 clinical testing in the U.S. for COVID-19 and could potentially advance to Phase 2/3 efficacy trials this summer. 

How it works

  • it delivers DNA into cells by using electrical pulses to open small pores in the cell.
  • allow the plasmid to enter into cells. 
  • Inside cell plasmid replicating thereby strengthening the immune system.

Advantages 

  1. Don’t interfere or changing the individual’s own DNA.
  2. This shows functional antibody response and T-cell responses following immunization.

4. LV-SMENP-DC vaccine

Based on a detailed analysis of the viral genome and search for potential immunogenic targets, a synthetic minigene has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease this is used by China. The infection of Covid-19 is mediated through the binding of the Spike protein to the ACE2 receptor, and the viral replication depends on the molecular mechanisms of all of these viral proteins.

It uses those cells produced from lentivirus responsible for HIV-like disease that activate immunity.

How it works

  • they use vector system to express viral protein like S protein 
  • modulate genes to modify dendritic cells (DCs) and to activate T cells. 
  • By this, the process cells will have different antigens and will be good for getting an immune response.

5. Pathogen-specific aAPC vaccine

 Based on a detailed analysis of the viral genome and search for potential immunogenic targets, a synthetic minigene has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease. The infection of Covid-19 is mediated through binding of the Spike protein to the ACEII receptor, and the viral replication depends on the molecular mechanisms of all of these viral proteins.

Antigen-presenting cells (APCs) are a group of immune cells that mediate the cellular immune response by processing and presenting antigens for recognition by certain lymphocytes such as T cells. Classical APCs include dendritic cellsmacrophages,Langerhans cells and B cells.

How it works

  • They use COVID-19 minigenes engineered and using a vector express this viral protein in the host cell
  • Immune modulatory genes to modify artificial antigen presenting cells (aAPC) and to activate T cells. 
  • By this artificial modification antigen produce and they produce antibody and immune response occur.

Despite the global efforts to develop an effective vaccine in response to the COVID-19 pandemic the earliest date one or more vaccines could be available is early to mid-2021. Despite numerous trials and significant funding, success within this timeline cannot be guaranteed, and mass production and distribution will be challenging and time consuming. Currently, there is no reliable drug regime to treat the infection. It is expected that effective treatment for COVID-19 will arrive sooner than a vaccine and one or more drugs may be approved over the coming months.

References.

Le, T.T., Andreadakis, Z., Kumar, A., Roman, R.G., Tollefsen, S., Saville, M. and Mayhew, S., 2020. The COVID-19 vaccine development landscape. Nat Rev Drug Discov19(5), pp.305-6.

https://clinicaltrials.gov/ct2/show/NCT04276896

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