Developing Safer Vaccines With Next Generation Sequencing

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Next generation sequencing (NGS) is a high-throughput technology that has revolutionised biological sciences and vaccine development.

In December 2019, a new coronavirus (SARS CoV-2) emerged in China. In a matter of months, it brought our modern world to a screeching halt. Many countries chose to go into lockdown to protect the population.

The race to find a vaccine began almost immediately.

Vaccine development

Vaccine development is normally a lengthy and expensive process. It can cost billions of dollars and take over 10 years to complete. Some 94 percent of vaccines never even make it past the development process.

The rise in infectious agents with the potential to cause global disruption, such as SARS CoV-2, has meant that this traditional timeline has been sped up.

Infectious agents such as viruses, however, tend to mutate at a rapid and consistent rate. These changes, or mutations, can alter the structure of the virus and its behaviour, ultimately affecting the way in which it is transmitted and how it attacks the human body.

An important part of developing a vaccine is having the ability to perform fast whole-genome sequencing (WGS) on viruses. This allows us to understand the DNA makeup of a virus, therefore both saving lives by facilitating the design of therapies and vaccines to combat the virus, and also helping scientists to understand how a vaccine may affect the human body.

WGS of the SARS CoV-2 has been key in the design of many of the vaccines recently launched.

Whole-Genome Sequencing (WGS)

Using WGS, scientists are able to determine the complete DNA, or RNA, sequence of an organism. Sanger sequencing, a traditional method of DNA sequencing, was first developed in the 1970s by Frederick Sanger and his colleagues. It is best for analysing a small number of samples and gene-targets. For over 40 years, it was the most widely used method. At a cost of approximately $3 billion, however, it took scientists 13 years to sequence most of the human genome using this technique. This was an expensive, time-consuming, and labour-intensive process. This long-time frame consequently lengthens the time it takes to identify the virus and thus delays treatment development. Today, due to the emergence of next generation sequencing, the cost of sequencing a whole genome has dropped to just about $1,000 and the time has been reduced to just a few days.

Next Generation Sequencing and vaccine development

Next generation sequencing (NGS) is a high-throughput technology that has revolutionised the biological sciences. NGS is an umbrella term that encompasses a number of new methods that are able to sequence (or read) DNA from a large number of samples in parallel, and with high accuracy. With NGS, scientists can sequence large amounts of DNA in a matter of days instead of weeks. It is this speed and accuracy that has allowed scientists to rapidly sequence the new coronavirus and identify potential vaccines.

Being able to test numerous vaccine candidates in a high-throughput manner helps scientists to better understand how a particular vaccine can affect the human body. This means that as a vaccine is being developed and tested, information about the way in which it interacts with the virus and our bodies is constantly being collected and analysed. Thus, not only can NGS be used in the early stages of vaccine development, but it can also be used to determine vaccine effectiveness.

NGS and virus mutations

With NGS, a full picture of viral transmission, mutation development, and epidemiology is being determined at a rapid rate, allowing researchers to develop and adapt treatments.

Most testing methods used to detect the presence of a virus (such PCR tests used to detect the new coronavirus) only look for the presence of a part of the virus. However, if this portion of the pathogen changes through mutation, then the test is no longer valid. Due to the speed and accuracy with which a sequence can be obtained, NGS can easily be used to track virus mutations.

This provides scientists with vital information about how the virus is being transmitted, which parts are important for its transmission, and which parts are responsible for the development of severe symptoms.

This is especially important when considering the fact that some members of the population do not develop symptoms when infected. Understanding the way in which the virus interacts with their immune systems aids in vaccine development and predicting who may develop severe symptoms following infection. Tracking mutations of a virus also ensures that any vaccine being used is effective against the most current form of the virus.

NGS for you and me

NGS is an accurate, high-throughput method of sequencing DNA. It is currently being used to speed-up traditional vaccine development timelines and track the spread of viruses such as the new coronavirus. Not only is it cheaper than traditional methods of sequencing, but it also reduces the time it takes to reach first in-human trials.

 

Sources:

Behjati S, Tarpey PS, What is next generation sequencing?Archives of Disease in Childhood – Education and Practice 2013;98:236-238.

Charre C, et al, Evaluation of NGS-based approaches for SARS-CoV-2 whole genome characterisation, Virus Evolution, 2020, 6(2)

Gouglas D, et al, Estimating the cost of vaccine development against epidemic infectious diseases: a cost minimisation study, The Lancet: Global Health, 2018, 6(12):1386-1296

Luciani F, et al, Next generation deep sequencing and vaccine design: today and tomorrow, Cell Press, 2012, 30(9):443-452

McNamara RP, et al, High-Density Amplicon Sequencing Identifies Community Spread and Ongoing Evolution of SARS-CoV-2 in the Southern United States, Cell Reports, 2020, 33(5)

Next Generation Sequencing 101

What is Next-Generation Sequencing (NGS)?, Thermo Fisher

Next-Generation Sequencing: Tracking the Spread and Evolution of SARS-CoV-2, Technology Networks

How Next-Generation Sequencing Is Helping to Build Better Vaccines, Breakthroughs

Ancestry Launches AncestryHealth Powered by Next Generation Sequencing (NGS), Business Wire

Further reading:

CRISPR: The Genetic Scissors by

Allergies et Intolérances : Quelle est la différence ? by

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Canva

 

Elinam Gayi Elinam Gayi

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