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Shooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development
Open accessAbstract
Since late 2019 the newly emerged pandemic SARS-CoV-2, the causative agent of COVID-19, has hit the world with recurring waves of infections necessitating the global implementation of non-pharmaceutical interventions, including strict social distancing rules, the wearing of masks and the isolation of infected individuals in order to restrict virus transmissions and prevent the breakdown of our healthcare systems. These measures are not only challenging on an economic level but also have a strong impact on social lifestyles. Using traditional and novel technologies, highly efficient vaccines against SARS-CoV-2 were developed and underwent rapid clinical evaluation and approval to accelerate the immunization of the world population, aiming to end the pandemic and return to normality. However, the emergence of virus variants with improved transmission, enhanced fitness and partial immune escape from the first generation of vaccines poses new challenges, which are currently being addressed by scientists and pharmaceutical companies all over the world. In this ongoing pandemic, the evaluation of SARS-CoV-2 vaccines underlies diverse unpredictable dynamics, posed by the first broad application of the mRNA vaccine technology and their compliance, the occurrence of unexpected side effects and the rapid emergence of variations in the viral antigen. However, despite these hurdles, we conclude that the available SARS-CoV-2 vaccines are very safe and efficiently protect from severe COVID-19 and are thereby the most powerful tools to prevent further harm to our healthcare systems, economics and individual lives. This review summarizes the unprecedented pathways of vaccine development and approval during the ongoing SARS-CoV-2 pandemic. We focus on the real-world effectiveness and unexpected positive and negative side effects of the available vaccines and summarize the timeline of the applied adaptations to the recommended vaccination strategies in the light of emerging virus variants. Finally, we highlight upcoming strategies to improve the next generations of SARS-CoV-2 vaccines.
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![Figure 1 Table of Variants characterized as Variant of concern (VOC), Variant of interest (VOI) or Alerted Variant by the World Health Organization (WHO). Left panel: shown is the Greek letter nomenclature as introduced by May 2021, the Pango nomenclature together with the date and location of the earliest documentation of a detected sample of the respective variant. Middle panel: List of the characterizing mutations based on their location in the N-terminal domain (NTD), receptor binding domain (RBD) or stalk region. Right panel: The crystal structure of the Spike protein trimer in closed conformation (PDB: 6ZGI) and an illustration of the mutated residues based on their location in the NTD, RBD or stalk region. Mutations that have been reported to confer immune escape are highlighted in orange. NTD zoom in: the NTD supersite, as described by McCallum et al. [12], is highlighted in lighter green.](/paper-figures/0c5d2857b3d24729846bb6002148ced8/shooting-at-a-moving-targeteffectiveness-and-emerging-challenges-for-sars-cov-2-figure-1.jpg)
![Figure 2 Timeline of the number of worldwide detected SARS-COV-2 cases (blue) and administered vaccination doses (grey), the time point of designation as a VOC or VOI by the WHO as well as key dates during the development of currently approved vaccines based on their technology: mRNA vaccines (orange), adenovirus-based vaccines (blue) and recombinant protein vaccines (grey). Given is the timeframe from the outbreak report of SARS-CoV-2 by the WHO in December 2019 until September 2021. Data taken from ‘Our world in data’ (September 2021) [104]. CP = clinical phase, Appr. = Approval, EUA = emergency use authorization, FA = Full approval.](/paper-figures/1aa096aed6864302b84d7d88cf19f322/shooting-at-a-moving-targeteffectiveness-and-emerging-challenges-for-sars-cov-2-figure-2.jpg)
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“Real-world data showed that effectiveness of mRNA-1273 against Alpha and Beta variants was 100% and 96.4%, respectively,417,418 whereas effectiveness against Delta was slightly lower (73.1%).102”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [418]
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Metadata
- Authors
- Günl, F., Mecate-Zambrano, A., Rehländer, S., Hinse, S., Ludwig, S., & Brunotte, L.
- Affiliations
- University of Münster (DE)
- Institute of Virology (IVM), University of Münster, 48149 Münster, Germany
- Corresponding author
- Brunotte, Linda
- Venue
- Vaccines
- Publisher
- MDPI AG
- Published
- 2021-09-22
- Volume
- 9
- Issue
- 10
- Pages
- 1052
- ISSN
- 2076-393X (ISSN-L)
- PMC
- PMC8540924
- OpenAlex
- W3199631570
- Cited by
- 27
- References
- 200
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 9 · 2022: 12 · 2021: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Vaccines (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- URN:NBN Resolver for Germany & Switzerland (German National Library) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (BR 5189/1-1)
- Clinical Research Unit (CRU342)
- Bundesministerium für Bildung und Forschung (01KI20218)
- Network University Medicine (01KX2021)
- Interdisciplinary Centre for Clinical Research (IZKF) (Bru2/015/19)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, COVID-19 vaccines, vaccine development, mRNA vaccines, vaccine side effects, vaccine effectiveness, SARS-CoV-2 variants, immune evasion, vaccine approval, vaccination strategies, vaccine safety
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