Is the development of an evolution-proof vaccine on the horizon?

Is the development of an evolution-proof vaccine on the horizon?

The tremendous influence that the COVID-19 pandemic has had on cancer research and cancer care is not unknown to most cancer researchers and physicians. Over the last couple of years, tackling the pandemic has become the main priority; hauling urgency from cancer care and the development of new approaches to treat cancer. Consequently, the delay in diagnosis and treatment administration for cancer patients has increased cancer-related deaths

Likewise, solving the SARS-CoV-2 puzzle became the main priority for many researchers that joined forces to understand the new respiratory illness.

For instance, researchers from Leiden Academic Centre for Drug Research (LACDR), were able to incorporate COVID-19 research projects into their current research scope which aims to explore new concepts and methods for drug delivery and vaccination. 

Similarly, the new virus spurred creative ways in cancer researchers to apply specialised skills and knowledge obtained over years of cancer research to COVID-19 research. 

While cancer and COVID-19 are very distinct diseases in their origin, progression and clinical manifestation; there is a common denominator that plays a pivotal role in thwarting their progression and promoting their eradication: the immune system.

COVID-19 and cancer immunology.         

Viruses bear foreign antigens which are recognised as a threat by the immune system triggering a series of immune responses aimed at eradicating the infection. These include antibody production (the so-called humoral immune response) and memory formation for faster immune response in potential future infections which form the basis of vaccinology.

Learning from insights on antigen-elicited immune responses acquired over the years, tumour immunologists realized that similarly to foreign antigens, cancer seemed to elicit an antigen-specific immune response.  

The ‘foreignness’ of cancer cells emanates from their high mutation-driven nature coupled to the expression of neoantigens, in other words, their ability to express new tumour antigens which are distinct from antigens expressed on normal cells – commonly known as self-antigens.

Fundamentally, the immune system is designed to not recognize self-antigens as this could result in the development of autoimmune diseases. 

Nevertheless, this otherwise incredibly beneficial mechanism of protection that is conserved among vertebrates and (simplified) in invertebrates exposes one of the biggest limitations in the field of cancer vaccinology.

COVID-19 and cancer vaccinology.

As you can imagine cancer cells, which largely emanate from normal cells, mainly express self-antigens. The latter are not ideal targets for vaccine-based immunotherapy, due to the immune system ignoring self-antigens.

Similarly to the emergence of new SARS-CoV-2 variants due to mutations, the high mutational burden in tumours also exposes a limitation to vaccine development. In this respect, the wide variety of mutated proteins and neoantigens hinders researchers that try to find the “antigen bullet” eliciting a long-lasting cellular and humoral immune response after administration of cancer vaccines with curative intent.

However, the limitations exposed by tumour antigens selection incited creative ways for cancer vaccine design.

CimCure’s iBoost vaccine design consists of a vasculature self-antigen coupled to a bacterial peptide. The latter confers the trigger for the immune system, overcoming the limitation exposed by self-antigens expression on cancer cells. On account of this new development for cancer vaccines, researchers at CimCure and Amsterdam UMC soon realized that by finding conserved regions in the genome of coronavirus variants, the iBoost technology could be transformed into a vaccine against the SARS-CoV-2 and future variants expressing the conserved antigen.

‘’This could potentially result in the development of an evolution-proof vaccine not only against future coronavirus variants but also other viruses such as seasonal influenza’’ says Dr Arjan Griffioen, Professor of Experimental Oncology and Angiogenesis at Amsterdam UMC and Founder and Chief Scientific Officer at CimCure (The Netherlands).

Furthermore, the pandemic did not only bring a new perspective to vaccine development but also cultural views on vaccination. The great effectivity and collaboration that the scientific community showed during the development of vaccines against COVID-19 have changed societal views on vaccination.

“After the pandemic, the trust in vaccines has raised enormously’’ says Dr. Arjan Griffioen.

However, statistics show that there is still mistrust in vaccination programs against the new virus. For instance, various surveys suggest that at least 40% of the Dutch population oppose getting vaccinated against COVID-19. Successful cancer vaccine development with curative intent is still very dismal, however, we hope that by looking at the success of preventive cancer vaccines (i.e the vaccine against HPV, the causative agent of cervical cancer), the hesitancy to get vaccinated in the general population will diminish overtime.

References

[1]          Kourie HR, Eid R, Haddad F, Ghosn M, Sarkis DK. The future of cancer research after COVID-19 pandemic: Recession? Future Oncology 2020;16:1493–5. https://doi.org/10.2217/fon-2020-0397

[2]          Abramo G, D’Angelo CA, Mele I. Impact of Covid-19 on research output by gender across countries. Scientometrics 2022. https://doi.org/10.1007/s11192-021-04245-x

[3]          Han HJ, Nwagwu C, Anyim O, Ekweremadu C, Kim S. COVID-19 and cancer: From basic mechanisms to vaccine development using nanotechnology. International Immunopharmacology 2021;90. https://doi.org/10.1016/j.intimp.2020.107247

[4]          Fox L, Beyer K, Rammant E, Morcom E, van Hemelrijck M, Sullivan R, et al. Impact of the COVID-19 Pandemic on Cancer Researchers in 2020: A Qualitative Study of Events to Inform Mitigation Strategies. Frontiers in Public Health 2021;9. https://doi.org/10.3389/fpubh.2021.741223

[5]          Finn OJ. Introduction to the special issue: Tumor antigens in the time of the coronavirus pandemic. Seminars in Immunology 2020;47:101396. https://doi.org/10.1016/J.SMIM.2020.101396

[6]          How COVID-19 impacts cancer research and treatment – Harvard Gazette n.d. https://news.harvard.edu/gazette/story/2020/10/how-covid-19-impacts-cancer-research-and-treatment/ (accessed March 7, 2022)

[7]          How Leiden’s drug pioneers have switched to Covid research - Leiden University n.d. https://www.universiteitleiden.nl/en/news/2020/06/how-leidens-drug-pioneers-have-switched-to-covid-research (accessed March 7, 2022)

[8]          Can our research contribute to find solutions for COVID-19? n.d. https://www.amsterdamumc.org/en/research/institutes/cancer-center-amsterdam/news/-can-our-research-contribute-to-find-solutions-for-covid-19-.htm (accessed March 7, 2022)

[9]       Saupe F, Huijbers E, Hein T, Femel J, Cedervall J, Olsson A et al. Vaccines targeting self-antigens: mechanisms and efficacy-determining parameters. The FASEB Journal. 2015;29(8):3253-3262

[10]     Pollard A, Bijker E. A guide to vaccinology: from basic principles to new developments. Nature Reviews Immunology. 2020;21(2):83-100

[11]     Amsterdam, U., 2022. How do we explain mistrust of the corona vaccine?. [online] University of Amsterdam. Available at: <https://www.uva.nl/en/shared-content/faculteiten/en/faculteit-der-maatschappij-en-gedragswetenschappen/news/2020/12/how-do-we-explain-mistrust-of-the-corona-vaccine.html?cb> [Accessed 30 March 2022]

[12]       Study Confirms HPV Vaccine Prevents Cervical Cancer - National Cancer Institute n.d. https://www.cancer.gov/news-events/cancer-currents-blog/2020/hpv-vaccine-prevents-cervical-cancer-sweden-study (accessed March 30, 2022)