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On the boundary of knowledge

Nikhil Faulkner discusses his immunogenicity work with SARS-CoV-2 variants and how the pandemic is changing the nature of research.

Vaccination will be key to the success of the global response to the COVID-19 pandemic. However, an important determining factor is achieving an improved understanding of the threats posed by emerging variants of SARS-CoV-2 and the degree of heterotypic immunity these variants can induce.

A major advance in meeting this challenge was achieved recently by a global collaboration of 29 researchers. Their paper, “Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains”, describes how they examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the UK in September 2020 and has been detected in more than 50 countries. The study found that “antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant.”

Immunogenicity

The study’s lead author Nikhil Faulkner, PhD student at London’s Francis Crick Institute, explained the implications of his team’s findings. “If we are going to live with COVID-19, we must accept that new variants will arise globally, and we will be exposed to them. Depending on our previous exposure to SARS-CoV-2 variants, our research cautions that we may be more susceptible to infection from one of these novel variants. Those infected with the virus will not know which variant infected them, so it is critical that eligible individuals get vaccinated as vaccines confer protection to varying degrees against disease caused by all known variants.”

He notes that viral immunologists now have an opportunity to observe the development of the immune response to a new virus in coming years, which “could help inform us with regards to vaccine design to protect us against future pandemics,” he says, “we may also gain clues as to how to better vaccinate against other viruses like influenza.”

Technical challenges

One of the challenges of the SARS-CoV-2 variant study was accessing material, as it is not standard practice to sequence the infecting virus upon a positive test result for SARS-CoV-2 outside of hospitals. Faulkner explains: “We collaborated with University College London Hospital, acquiring serum samples from patients with known B.1.1.7/Alpha variant infection. Likewise, with cases of B.1.351/Beta infection in the UK, we obtained the authentic virus isolate from collaborators in South Africa, where the strain was first described. The work was a huge collaboration, which would have been impossible without a global effort.”

A further challenge, adds Faulkner, was that most of their work was undertaken during the Christmas/post-Christmas UK lockdown, “when many of my colleagues had to isolate for various reasons at different stages of the research.”

A positive change has been the willingness for groups to collaborate

The pace of COVID-19 research

Faulkner’s PhD – due for completion by March 2022 – explores immune responses to viral vectors for gene therapy, concentrating on the humoral response to these vectors when introduced into the blood and lungs in the context of cystic fibrosis. However, Faulkner has demonstrated how crucial adaptability is to scientific progress: “During my research, I was using an antibody assay, which a team of us repurposed to study humoral responses to SARS-CoV-2, which led to us studying the degree of cross-reactivity in antibody responses between SARS-CoV-2 variants.”

But to what extent has the global demand for speedily acquired COVID-related research knowledge impacted how research is undertaken? “A positive change has been the willingness for groups to collaborate, traceable to the urgency around the pandemic. With little time to learn a new lab technique, researchers collaborate with others who are experts in that technique. Luckily, inter-laboratory collaboration within the Crick was encouraged even before the pandemic. I think research works best when we’re united as a field and the success of science throughout the pandemic proves that.”

Another COVID-19-related development that Faulkner identifies is the rise of pre-prints: “These arose from the urgency around the pandemic, with labs choosing to share their data promptly for the benefit of the wider community. This has been beneficial, speedily disseminating information that can help support or undermine hypotheses. However, in the absence of peer review it is critical to maintain the high standards that we expect and have grown accustomed to in scientific research to avoid misleading fellow academics and/or the public.”

Future COVID-19 research

Faulkner anticipates that future research avenues at the Francis Crick Institute will include an undertaking to further understand how infection with one SARS-CoV-2 variant affects immunity to other variants. “This,” he suggests, “is important as it will help inform vaccine design. For example, we might see a multivalent vaccine in the future, delivering protection against multiple variants in a single shot.”

Looking further afield, Faulkner speculates that another key area for research that will be essential to ending the pandemic is making vaccines accessible and affordable to all regions of the world: “Developed countries must support less-developed nations battling this virus for the benefit of everybody globally. We all profit from the reduced spread of new variants worldwide”

And finally

With Faulkner’s PhD nearing completion, he harbours a keen sense of excitement about what lies ahead: “What is exciting about research is that you’re on the very boundary of knowledge. As researchers, we’re trying to understand and discover things that nobody has achieved or uncovered before. The idea that we contribute something new to the world is inspiring, and the thought that that contribution can influence the lives of others motivates me every day. However, there is a great challenge in expanding the boundaries of what we know and understand: if the answer was easy, it would already have been answered!”


Nikhil Faulkner

  • Undergraduate Master’s degree in Biochemistry from University of Oxford, July 2017
  • Awarded David Wing Prize for Excellence in Biochemistry, July 2017
  • Began PhD at Francis Crick Institute, September 2017
  • Awarded Sir David Cooksey Prize in Translational Medicine for work undertaken during COVID-19 pandemic, December 2020.

 

Image credit | Getty

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