Abstract
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.
Highlights
SARS-CoV-2 is a member of severe acute respiratory syndrome-related coronaviruses that belongs to the betacoronavirus genus
Since the first reported emergence in Wuhan City, Hubei Province, China, in December 2019 extensive genome sequencing and data sharing have enabled tracing of SARS-CoV-2 outbreaks and global spreading, as well as the real-time detection of mutations in the viral genome that led to the emergence of new SARS-CoV-2 variants [2,9,10]
The determinants for variants of concern (VOC)/variants of interest (VOI) classification are amino acid (AA) variations in the S protein, which facilitates binding to the cellular receptor angiotensin converting enzyme 2 (ACE2) and is exposed as trimers on the viral surface
Summary
SARS-CoV-2 is a member of severe acute respiratory syndrome-related coronaviruses that belongs to the betacoronavirus genus (subgenus: sarbecovirus). The broadly discussed deletion of positions H69/V70, which is found in the Alpha variant and independently occurred in some isolates of other VOCs and VOIs, leads to increased infectivity mediated by enhanced spike cleavage [82] This deletion has not been shown to substantially contribute to escape from neutralization by mAbs [59,60,83]. For SARS-CoV-2 vaccines, the endpoints of phase III trials evaluated the efficacy of a specific vaccination regimen to prevent severe disease, hospitalization and death by comparison of a vaccinated test group with a placebo control cohort Other important criteria, such as the efficacy of protection from viral infection and virus shedding are less frequently evaluated and remain to be determined in real-world settings. The official version of this study is yet to be published
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