“COVID-19 has brought the world to its knees”^[1]

declaration from the Coalition for Epidemic Preparedness Innovations (CEPI)

+4.9 million dead^[2]

114 million jobs lost in 2020^[3]

$4.5 trillion worth of economic damages by 2025^[4]

The recent destructive outbreak of the novel coronavirus that emerged from China, and rapidly spread to Europe and North America, demonstrated beyond doubt the importance of investing in vaccine research to protect us against emerging infectious diseases which are a clear danger to the world population and its economy. Vaccines are a hot topic, with everyone now aware of their importance.

However, not many people understand the mechanism of how vaccines protect us: the immunological stimulus which is necessary to help our bodies fight the virus and build up immunity.

All vaccines contain two essential components: an antigen (“active ingredient”), against which the immune response is directed, e.g. a protein from an infectious agent or cancer, and an adjuvant which induces the desired type of immune response, e.g. antibodies or ‘killer’ cytotoxic T cells.

Components of vaccines; image taken from What’s in a vaccine?, British Society for Immunology

Vaccine adjuvants determine the quantity and quality of the immune response that can be mounted against any given infectious agent and contribute to the induction of immunological memory which is needed for longer-term protection. Currently available adjuvants may not induce the most optimal levels or types of immune responses needed for full protection, creating a need for a new class of adjuvants that promote durable and long-lasting immunological memory. Additionally, certain vaccines require extreme cold-chain conditions to maintain their effectiveness.

Properties of vaccine adjuvants; image adapted from S. R. Bonam et al.,

Trends in Pharmacological Sciences, 2017, 38, 771-793.

Adjuvants can be organic in nature, such as agonists that mimic components of infectious agents (e.g. RNA or DNA encoding the proteins), but the resulting vaccines have to be stored and transported at exceptionally low temperatures (e.g. -70°C for Pfizer-BioNTech and -20°C for the Moderna COVID vaccine) to stay viable. As a result of this, the required cold-chain makes it challenging to deliver and administer such vaccines in remote rural and/or underdeveloped areas. 

Another organic adjuvant that received public attention in the fall of 2020 is squalene, derived from shark liver oil.^[5] Unfortunately, squalene can only be harvested from the animal and not synthetically produced, significantly limiting its commercial application in vaccines.

More than 70% of the approved vaccines on the market use an inorganic adjuvant in combination with a protein-based antigen instead of the new RNA-based vaccine technology. Such vaccines are stored under normal refrigerated (from 2°C to 8°C) conditions rather than frozen, significantly expanding their applicability across all geographies. There is, so far, only one class of inorganic adjuvants used, called alums, which are heterogenous (amorphous and crystalline) and poorly defined aluminium salt-based compounds. These are particularly useful for inducing antibody responses – potent for extracellular pathogens – but they do not stimulate a strong cellular immune response often needed for intracellular pathogens such as viruses. This renders alum adjuvanted vaccines less effective, or even ineffective, against many viral infections, such as COVID. There is an urgent, unmet need for effective adjuvants that can selectively induce different types of immunity to improve current vaccines effectiveness and develop new vaccines for different types of infectious diseases (and cancers).

Researchers at Oxford University have previously shown that layered double hydroxides (LDHs) can possess adjuvant functionality by stimulating robust and different types of immune responses depending on their chemical composition.^[6]  LDHs are well defined crystalline, inorganic compounds that contain a sandwich of positively charged mixed-metal hydroxide layers (containing both a trivalent [M³⁺] and either a monovalent [M⁺] or divalent [M²⁺] cation) with interlayers of negatively charged anions. These are homogeneous materials that can be synthesized across a wide range of chemical compositions, in different sizes (i.e. nm – mm) and in different morphologies (e.g. platelets or coral-type). LDHs are safe and biocompatible, and some compounds are already FDA approved for ingestion as they are used in over-the-counter medications. Remarkably, the researchers have also demonstrated that the immunological properties of LDHs can be predicted purely from their physicochemical properties.

These findings open the possibility to synthesizing ‘tailored’ adjuvants which could be incorporated into vaccines designed for use in different disease settings. A vaccine to specifically target a certain virus or disease could be produced that utilised an LDH adjuvant that afforded the necessary potent immune response – antibodies in combination with strong intracellular response – required to fight it. By employing this new class of inorganic adjuvants, more effective, stable vaccines could be within reach.

If you have any interest in this area, contact us: info@cierra.com

References:

1. Coalition for Epidemic Preparedness Innovations, https://endpandemics.cepi.net/ (accessed November 2021).
2. WHO Coronavirus (COVID-19) Dashboard, World Health Organization, https://covid19.who.int/ (accessed November 2021).
3. ILO Monitor: COVID-19 and the world of work – Updated estimates and analysis, International Labour Organisation, 2021, https://www.ilo.org/wcmsp5/groups/public/@dgreports/@dcomm/documents/briefingnote/wcms_767028.pdf (accessed November 2021).
4. World Economic Outlook Update: Fault Lines Widen in the Global Recovery, International Monetary Fund, 2021, https://www.imf.org/en/Publications/WEO/Issues/2021/07/27/world-economic-outlook-update-july-2021 (accessed November 2021).
5. Coronavirus Vaccine Makers Are Not Mass-Slaughtering Sharks, The New York Times, 2020, https://www.nytimes.com/2020/10/13/science/sharks-vaccines-covid-squalene.html (accessed November 2021).
6. Williams et al., Journal of Experimental Medicine, 2014, 211, 1019-1025.