Shooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development

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.

DNA Vaccines Expressing the Envelope and Membrane Proteins Provide Partial Protection Against SARS-CoV-2 in Mice

“…A variety of SARS-CoV-2 vaccines are currently being developed and some have been approved, including inactivated-, subunit-, vector-, mRNA-, and DNA vaccines ( 13 , 14 ). Although several vaccines against COVID-19 are promising, developing more effective and cross-protective vaccines is urgently required.…”

Advances in COVID-19 mRNA vaccine development

“…415 , 416 Between December 28, 2020, and May 10, 2021, 256,037 people in Qatar received at least one dose of the mRNA-1273 vaccine, whereas 181,034 people received two doses. 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 Other studies have shown that mRNA-1273 is still quite effective in congregate settings or higher-risk exposure such as prisons or hospitals in which the Delta variant was prevalent.…”

Counting on COVID-19 Vaccine: Insights into the Current Strategies, Progress and Future Challenges

“…Initially, Sputnik V has faced lots of criticism for unseemly haste with low transparency, but the outcome and interim analysis reports published in the Lancet have attempted to do away with the allegations of non-transparency [ 84 , 86 , 87 , 88 , 89 , 90 ]. The Gamaleya Research Institute (Moscow, Russia) claimed that Sputnik V is more than 90% effective against the B.1.617.2 variant of CoV [ 91 ].…”