Jun 4, 2021

Thermo Fisher: tracking COVID-19 variants

covid-19
virus
virusmutation
covid-19vaccine
5 min
Thermo Fisher's Senior Medical Director Manoj Gandhi tells us how they monitor new COVID-19 virus strains

The Delta variant of COVID-19 (formerly known as the Indian variant) is continuing to spread around the world, with the WHO now estimating it to be present in 62 countries

SARS-CoV-2, the virus that causes COVID-19, is believed to be mutating every 11-15 days - roughly half the rate of the common flu. So far 12,700 mutations have been identified, along with 4000 variants. 

Lab supplier Thermo Fisher Scientific recently launched the TaqMan Mutation panel, which  can test confirmed infected samples for COVID-19 variants. We ask Manoj Gandhi, Thermo Fisher's Senior Medical Director, how the virus is mutating, how to monitor this, and whether it is becoming more transmissible. 

Is SARS-CoV-2 mutating at a faster rate than most viruses? 
It is normal for viruses to mutate. Whether the mutation rate is faster or slower depends on the type of viruses being compared. SARS-CoV-2 is an RNA virus, and compared to DNA viruses such as herpes viruses or pox viruses that can proof-read and fix genetic errors as they divide, SARS-CoV-2 lacks the robust proof-reading machinery. 

This means it mutates at a faster rate than DNA viruses. In comparison to other RNA viruses such as influenza viruses or HIV, coronaviruses have slightly better genetic proofreading machinery. Therefore, in theory, SARS-CoV-2 is expected to have a slightly lower mutation rate than the flu viruses or HIV. 

However, the unmitigated spread of the virus and several large scale outbreaks have offered multiple opportunities for the SARS-CoV-2 to divide and accumulate mutations as it replicates. In addition, some of the treatments such as convalescent plasma or even vaccinations may lead to selection pressure for the virus to mutate faster than expected.

What is the usual process for monitoring viral mutations, and how does monitoring for SARS-CoV-2 mutations compare? 
The conventional method is by sequencing the viral genome on a random set of positive samples using Next Generation Sequencing (NGS). This approach allows you to examine the entire sequence of the viral genome and helps identify already “known” viral strains circulating in the community as well as any “new” strains that may have emerged. 

Another approach taken by some public health labs is to use a two-step approach using mutation assays. In this approach, the first step involves testing a positive sample with a set of PCR-based mutation assays for already known SARS-CoV-2 variants. If one or more of the mutations in the set is present, it could help identify the known strain type. If none of the mutations in the set are present, then step 2 involves testing the sample with NGS for determining which other strain may be present or if it is a novel strain. 

The two-step approach allows to scale up SARS-CoV-2 variant surveillance so that more samples can be tested and sequencing capabilities can be conserved for when they are absolutely required. Laboratories are also using the “S-gene drop out” feature of the TaqPath™ COVID-19 Combo Kit as an indirect indicator of the presence of the B.1.1.7 (UK) variant.

How quickly can the TaqMan Mutation assay detect a new variant?
To be clear, the TaqMan Mutation assay is useful for identification of “known” SARS-CoV-2 variants. It's a PCR-based approach that uses already extracted sample RNA and existing PCR instruments. Typically, the turn-around-time for the TaqMan Mutation assays, from extracted RNA to results, is about 1 hour. For “new” variants, one needs to resort to sequencing.

How much do we know about the Delta variant, in terms of how transmissible it is, and whether the vaccines we have are effective against it?
As far as transmissibility is concerned, the Indian variants, especially the B.1.617.2 and B.1.617.3 variants, are more transmissible than the wild type SARS-CoV-2 virus. This property of increased transmissibility of the B.1.617.2 and B.1.617.3 are conferred upon by the specific mutations such as the L452R and E484Q present in these variants. 

While it's difficult to compare the transmissibility of the Indian variants against other variants, Public Health England (PHE) has suggested that the B.1.617.2 variant may have equal or greater transmissibility than the B.1.1.7 (UK) variant. As a result of this increased transmissibility, PHE has escalated B.1.617.2 to a “Variant of Concern”. 

Similarly, the WHO has categorised B.1.617.3 as a “Variant of Concern” due to the increased risk of transmissibility. While there are concerns over whether the mutations in the Indian variant can confer immune resistance, recent scientific evidence suggests that two doses of the Pfizer and AstraZeneca vaccines after (PHE study) are effective against the variants in preventing severe disease and deaths. In another lab-based study conducted by a New York University, the Pfizer and the Moderna vaccines showed that, in principle, they are effective against them. 

Will it be necessary to develop additional vaccines to combat new variants?
At present, the current vaccines for COVID-19 appear to be effective against the SARS-CoV-2 variants. As the virus evolves and undergoes additional mutation, there is always a risk that a mutation might occur and a “breakthrough variant” might emerge that could confer resistance against the current vaccines.

If that were to occur, additional vaccines would need to be developed against the new variants. Hence, it is critical to perform SARS-CoV-2 surveillance to monitor the spread of current variants as well as identify any new variants that might emerge with potential to evade vaccines.

Will we need annual vaccinations for COVID-19, like the yearly flu vaccine? 
Current scientific evidence points to two mechanisms of immune protection against the virus: cell mediated (T-cell) and antibody-mediated (B-cell) response. While the exact duration of immune protection is not known, scientific literature suggests that the B-cell antibody response provides a protective effect from about 6 months to a year whereas T-cell immune response provides a longer lasting response. 

While it is unclear at this point if annual vaccinations for COVID-19 would be recommended, it appears that there is a possibility that additional booster doses could be required to replenish the antibody-mediated immune response, at least in the subsequent years.

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Jun 22, 2021

Bachem turns 50 - a timeline

pharma
supplychain
peptides
medication
3 min
As Bachem turns 50, we take a look at the company's history

Bachem, a supplier to pharmaceutical and biotechnology companies worldwide, is celebrating its 50th anniversary this month. We take a look at the Swiss company's history.  

1971 - beginnings

Bachem is founded by entrepreneur Peter Grogg in Liestal, a small town near Basel in Switzerland. Grogg started the firm with just two employees, and with a focus on peptide synthesis - peptides are composed of amino acids that have a variety of functions treating health conditions such as cancer and diabetes. 

1977 - 1981 - early growth

Bachem moves its headquarters to the Swiss town of Bubendorf, with eight employees. In 1978 the company produces peptides for use in medicines for the first time. In 1981 production capacity triples and the workforce grows to 150. 

 1987 - 1996 - worldwide expansion

The company expands into the US with Bachem Bioscience, Inc. in Philadelphia. To strengthen its presence in Europe, Bachem opens sales and marketing centres in Germany in 1988. 

Further sales centres open in France in 1993. By 1995 the company employs 190 people. In 1996 it acquires the second largest manufacturer of peptides in the world and forms Bachem California with a site in Torrance. 

 1998 - 2003 - Bachem goes public

Bachem company goes public and lists shares on the Swiss Stock Exchange. Further acquisitions include Peninsula Laboratories, Inc, based in California, and  Sochinaz SA, a Swiss-based manufacturer of active pharmaceutical ingredients.  By 2001, the company has 500 employees and sales reach 141 million CHF.

In 2003 the organisation is given a new legal holding structure to support its continued growth, which remains in place to this day. 

2007 - 2013 - acquisitions

Bachem acquires a brand by Merck Biosciences for ready-to-use clinical trial materials and related services. 

In 2013, together with GlyTech, Inc. Bachem announces the development of a new amino acid that can help to treat multiple sclerosis, with a world market of more than $4 billion. 

In 2015 it acquires the American Peptide Company (APC), which becomes integrated into Bachem Americas. 

2016 - 2019 - a global leader

In 2016 the group opens a new building dedicated to R&D projects and small series production in Bubendorf. With a total of 1,022 employees, the workforce exceeds the 1,000 mark for the first time in the company’s history. Sales are over the 200 million mark for the first time at 236.5 million CHF.
Bachem expands into Asia with the establishment of a new company in Tokyo called Bachem Japan K.K. 

By 2019 Bachem has a growing oligonucleotide portfolio - these are DNA molecules used in genetic testing, research, and forensics. It is hoped this will become a significant product range in the future. 

2020 - COVID-19

Despite the COVID-19 pandemic, Bachem secures its supply of active ingredients, and even increases it in critical areas. Sales exceed the 400 million Swiss franc mark for the first time, and  272 new employees are hired.  

2021 - a milestone anniversary

Bachem celebrates its 50th anniversary and position as a global leader in the manufacture of peptides. While it  remains headquartered in Bubendorf, the company employs 1,500 people at six locations worldwide. In the next five years there are  plans to continue expanding. 

Commemorating the company's anniversary, Kuno Sommer, Chairman of the Board of Directors, said: "Bachem's exceptional success story from a small laboratory to a global market leader is closely linked to Peter Grogg's values, and has been shaped by innovation, consistent quality and cost awareness, as well as by entrepreneurial vision."

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