The search for a universal COVID-19 vaccine, effective against all present and future variants of coronaviruses is an imperative. The idea is to focus on the less-mutating, most conserved region of the virus, instead of the region that frequently mutates. The currently available adenoviral vector based, and mRNA vaccines use the viral spike protein as a target. Towards the pursuit for a universal COVID-19 vaccine, the novel nanotechnology-based SpFN Vaccine shows promise based on the pre-clinical safety and potency and the start of the phase 1 clinical trials.
COVID-19 disease caused by the SARS-CoV-2 virus has plagued the entire world since November 2019, causing approx. 7 million pre-mature deaths worldwide so far, an immense human suffering due to infection and lockdown and bringing economies of most of the countries to a complete standstill. The scientific community across the world has been striving hard to make safe and effective vaccines against the disease, ranging from the whole attenuated virus to DNA and protein conjugate vaccines1, targeting the spike protein of the virus. The latest mRNA technology also uses the transcribed spike protein of the virus to elicit an immune response. However, data on the vaccine effectiveness in the past year or so has shown that the protection conferred by the vaccines is less effective against the newly mutated VOC’s (Variant of Concern), as shown by many vaccine breakthrough infections, arising due to the mutations in the spike protein of the virus. The new variants seem to be more infective, and may cause less severe to more severe disease depending on the nature of mutations. The highly virulent delta variant, created havoc causing not only an increase in the number of infections, but also a higher rate of mortality. The newly reported Omicron variant from South Africa is 4 to 6 times more infectious, albeit causing less severe disease based on the current available data. The drop in effectiveness of the available vaccines against the new variants (and potential future variants), has forced scientists and the policy makers alike, to think of a universal COVID-19 vaccine that could be effective against all present and future variants of the coronaviruses. Pan-coronavirus vaccine or Universal COVID-19 vaccine refers to this.
In fact, there may be other variants present in communities, however, they will only be identified upon sequencing. The infectivity and virulence of these existing and/or new non-existing variants is unknown2. In the wake of emerging variants, the need to develop a pan-coronavirus vaccine is gaining importance.
The COVID-19 disease caused by SARS-CoV-2 virus is here to stay and we may not be able to get rid of it completely. In fact, humans have been living with Corona viruses that cause common cold, since the beginning of human civilization. The past two decades has seen four coronavirus outbreaks: SARS (severe acute respiratory syndrome, 2002 and 2003), MERS (Middle East respiratory syndrome, since 2012), and now Covid-19 (since 2019 caused by SARS-CoV-2)3. The main difference between the innocuous and other three strains that caused a disease outbreak is the enhanced ability of SARS-COV-2 virus to infect (higher affinity for human ACE2 receptors) and cause severe disease (cytokine storm). Whether the SARS-CoV-2 virus gained this ability naturally (natural evolution) or due to the evolution in the laboratory, based on research performed on the “gain of function” studies, that led to the development of this new strain and its possible accidental outbreak, is a question that remains unanswered till now.
The strategy suggested to make a pan-corona virus vaccine is to target the genomic region of the virus that is conserved and less likely to mutate. This will provide protection against the existing and the non-existing future variants.
One example of targeting a consensus region is to use RNA polymerase as a target4. A recent study found memory T cells in health care workers that were directed against the RNA polymerase. This enzyme, being the most conserved among the human coronaviruses that cause common cold and SARS-CoV-2), makes it an important target to develop a pan-coronavirus vaccine. Another strategy adopted by the Walter Reed Army Institute of Research (WRAIR), USA is to develop a universal vaccine, called Spike Ferritin Nanoparticle (SpFN), that uses a harmless portion of the virus to trigger body’s defences against COVID-19. The SpFN vaccine has been shown to not only confer protection against the Alpha and Beta variant in hamsters5, but also induces T cell and specific innate immune response in mice6 and non-human primates7. These preclinical studies demonstrate the effectiveness of the SpFN vaccine and lends support to the WRAIR’s strategy for the development of the pan-coronavirus vaccine8. The SpFN vaccine entered a Phase 1, Randomized, Double-blind, Placebo-Controlled trial on 29 participants to evaluate its Safety, Tolerability, and Immunogenicity. The trial started on April 5th 2021 and is expected to complete in 18 months by October 30th 20229. However, an early analysis of data this month will shed some light on SpFN’s potency and safety in humans8.
Use of attenuated virus (as it contains all the antigens; mutating as well as less mutating). However, this requires huge amounts of infective viral particles to be produced, requiring a BSL-4 containment facility for manufacturing, which may pose an unacceptable safety risk.
These approaches present a huge step forward in the urgent need to develop a safe and potent universal vaccine against SARS-CoV-2 and get the world out of this current situation, and bringing it back to normalcy as soon as possible.
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References:
- Soni R, 2021. Soberana 02 and Abdala: World’s first Protein conjugate Vaccines against COVID-19. Scientific European. Posted 30 November 2021. Available at http://scientificeuropean.co.uk/covid-19/soberana-02-and-abdala-worlds-first-protein-conjugate-vaccines-against-covid-19/
- Soni R., 2022. COVID-19 in England: Is Lifting of Plan B Measures Justified? Scientific European. Posted 20 January 2022. Available at http://scientificeuropean.co.uk/covid-19/covid-19-in-england-is-lifting-of-plan-b-measures-justified/
- Morens D M, Taubenberger J, and Fauci A. Universal Coronavirus Vaccines — An Urgent Need. NEJM. December 15, 2021. DOI: https://doi.org/10.1056/NEJMp2118468
- Soni R, 2021. “Pan-coronavirus” vaccines: RNA Polymerase Emerges as a Vaccine Target. Scientific European. Posted 16 November 2021. Available at http://scientificeuropean.co.uk/covid-19/pan-coronavirus-vaccines-rna-polymerase-emerges-as-a-vaccine-target/
- Wuertz, K.M., Barkei, E.K., Chen, WH. et al. A SARS-CoV-2 spike ferritin nanoparticle vaccine protects hamsters against Alpha and Beta virus variant challenge. NPJ Vaccines 6, 129 (2021). https://doi.org/10.1038/s41541-021-00392-7
- Carmen, J.M., Shrivastava, S., Lu, Z. et al. SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses. npj Vaccines 6, 151 (2021). https://doi.org/10.1038/s41541-021-00414-4
- Joyce M., et al 2021. A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates. Science Translational Medicine. 16 Dec 2021. DOI:10.1126/scitranslmed.abi5735
- Series of preclinical studies supports the Army’s pan-coronavirus vaccine development strategy https://www.army.mil/article/252890/series_of_preclinical_studies_supports_the_armys_pan_coronavirus_vaccine_development_strategy
- SARS-COV-2-Spike-Ferritin-Nanoparticle (SpFN) Vaccine With ALFQ Adjuvant for Prevention of COVID-19 in Healthy Adults https://clinicaltrials.gov/ct2/show/NCT04784767?term=NCT04784767&draw=2&rank=1
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