Nanomedicine’s finest hour

Nanotechnology played a central role in providing the first two authorised vaccines against the COVID-19 pandemic just nine months after its underlying SARS-CoV-2 virus spread across the world, turning the pandemic crisis into what may be regarded as nanomedicine’s finest hour.

Drs Steffi Friedrichs and Diana M. Bowman illustrate the technology’s enabling power in the Comment of the April 2021 issue of Nature Nanotechnology.

When, in November 2020, first the Moderna/National Institutes of Health (NIH) and then the Pfizer/BioNTech vaccines reported their successful (preliminary) results of phase III clinical trials in quick succession, there was noticeable surprise that these vaccines should not be based on the well-known and widely-employed live-attenuated vaccine (LAV) or inactivated vaccine (IV) designs, but on a new class of messenger RNA (mRNA)-based technology that had never before been approved for use in vaccines. Both the speed of R&D and the demonstrated efficacy against COVID-19 infections, which to this date outperforms most other hitherto authorised vaccine technologies, surprised not only those experts that had highlighted its ‘high risk of failure’ just three months prior to the vaccines’ approval, but also the wider field of public health officials, who had warned that ‘it may still take a year to 18 months to achieve the production and distribution of vaccines’.

To the nanotechnology community, however, the real story within the story is the manifold pivotal role that nanomedicine has played in the R&I of COVID-19 vaccines in general, and in the shooting-star success of the two mRNA vaccines in particular, which – as pointed out by the Comment’s authors – is based on a multitude of the state-of-the-art interdisciplinary attributes that nanomedicine offers. ‘It is the translational power between the biological world and the world of (materials) chemistry and engineering – the core underlying phenomenon of nanoscience and -technology – that sets nanotechnology apart as a key enabler of true 21^st century vaccine development platforms,’ says Dr Steffi Friedrichs, Director of the start-up AcumenIST.

This translational power has been identified by a number of vaccination experts to be one of the best responses to newly emerging epidemic diseases, as it allows the development of an entire virus-specific platform (from viral sequencing to clinical trials) in just four months.

‘The rapid succession of news about slow vaccine roll-out, novel variants and increasing infections, prompts a growing number of experts to drop the hope that herd immunity to COVID-19 may ever be reached; instead, they are starting to consider the possibility that we may need to prepare for living with reoccurring corona virus outbreaks. In this case, all steps from the identification of the virus to the discovery, development, production and administration of a highly efficacious vaccine need to be geared towards rapid response and high flexibility, whilst maintaining high throughput, quality and safety, and nanotechnology-enabled RNA vaccine platforms provide exactly that,’ Dr Friedrichs adds.

The key enabling effect of nanomedicine does not stop at providing lipid shells that protect and deliver the functional mRNA molecules of the two novel vaccines by Moderna/NIH and BioNTech/Pfizer; the protein-based technology of the Novavax vaccine (currently in phase III clinical trials), for example, relies on recombinant nanoparticles that mimic the structure of the coronavirus, without its infectious properties, as reported by the New York Times. In addition, the Comment highlights evidence that nanomedicine also has a role to play in the treatment of COVID-19 infections.

Moreover, both the flexibility of the nanotechnology-enabled vaccine platforms, and the regulators fast-track approval of the two mRNA vaccines harbour valuable benefits for vaccination needs in low-income countries, in which individuals are far more likely to die of a communicable disease than a noncommunicable disease, according to the World Health Organization. ‘Now that regulators around the world are familiar with the more versatile and affordable nanomedicine platforms, significant milestones in the understanding of both the needs and possibilities in fast-tracking vaccine R&D and authorisation have been achieved, especially with a view to more localized outbreaks of diseases in low- and middle-income countries,’ explains Dr Diana M. Bowman, Associate Dean and Professor at the Sandra Day O’Connor College of Law at Arizona State University.

Nevertheless, the reliance on the relatively novel discipline of nanomedicine in the world’s largest effort to provide a vaccine against a global pandemic is not without risk and somewhat foreseeable drawbacks, as it turns out that it is the synthesis of the lipid nanoparticle shells that represent the bottleneck in the production of both mRNA vaccines. According to the Comment’s authors, however, it is this role as the least developed innovation in vaccine value-chains that holds the potential for nanomedicine’s ‘coming of age as a global health tool’: ‘As the most immature step in an otherwise established high-volume production process, the relevant lipid nanoparticle innovations now receive the focus and investment required to reach the large-scale manufacturing and acceptance that nanomedicine has chased for decades in the field of cancer detection and treatment,’ Dr Friedrichs adds.

Written by: Dr. Steffi Friedrichs, Director of AcumenIST & Coordinator of NanoFabNet, Belgium.