Accelerated Development of COVID-19 Vaccines: Technology Platforms, Benefits, and Associated Risks

Abstract

Multiple preventive COVID-19 vaccines have been developed during the ongoing SARS coronavirus (CoV) 2 pandemic, utilizing a variety of technology platforms, which have different properties, advantages, and disadvantages. The acceleration in vaccine development required to combat the current pandemic is not at the expense of the necessary regulatory requirements, including robust and comprehensive data collection along with clinical product safety and efficacy evaluation. Due to the previous development of vaccine candidates against the related highly pathogenic coronaviruses SARS-CoV and MERS-CoV, the antigen that elicits immune protection is known: the surface spike protein of SARS-CoV-2 or specific domains encoded in that protein, e.g., the receptor binding domain. From a scientific point of view and in accordance with legal frameworks and regulatory practices, for the approval of a clinic trial, the Paul-Ehrlich-Institut requires preclinical testing of vaccine candidates, including general pharmacology and toxicology as well as immunogenicity. For COVID-19 vaccine candidates, based on existing platform technologies with a sufficiently broad data base, pharmacological–toxicological testing in the case of repeated administration, quantifying systemic distribution, and proof of vaccination protection in animal models can be carried out in parallel to phase 1 or 1/2 clinical trials. To reduce the theoretical risk of an increased respiratory illness through infection-enhancing antibodies or as a result of Th2 polarization and altered cytokine profiles of the immune response following vaccination, which are of specific concern for COVID-19 vaccines, appropriate investigative testing is imperative. In general, phase 1 (vaccine safety) and 2 (dose finding, vaccination schedule) clinical trials can be combined, and combined phase 2/3 trials are recommended to determine safety and efficacy. By applying these fundamental requirements not only for the approval and analysis of clinical trials but also for the regulatory evaluation during the assessment of marketing authorization applications, several efficacious and safe COVID-19 vaccines have been licensed in the EU by unprecedentedly fast and flexible procedures. Procedural and regulatory–scientific aspects of the COVID-19 licensing processes are described in this review.

Appraisal of SARS-CoV-2 mutations and their impact on vaccination efficacy: an overview

“…Before clinical trials, regulatory agencies should check production processes and information obtained from preclinical tests for vaccine safety assurance [154].…”

Übersicht über die in der EU zugelassenen COVID-19-Impfstoffe – von der Technologie über die klinische Prüfung zur Zulassung

“…Erfolgt dies nicht, kann die bedingte Zulassung widerrufen werden. Grundsätzlich sind bedingte Zulassungen für ein Jahr befristet, können aber jeweils jährlich verlängert werden und bei Vorliegen aller Datenpakete in eine reguläre Zulassung übergehen [ 42 , 43 ].…”

“…Der Effekt der Boosterimpfung basiert hierbei vor allem auch darauf, dass neben der Titererhöhung durch die Restimulation auch die durch somatische Hypermutation entstandenen Omikron-spezifischen Memory-B-Zellen stimuliert werden können und so eine Verbreiterung der Immunantwort beobachtet werden kann [38,39] [42,43]. Um die Zulassung von COVID-19-Impfstoffen bestmöglich zu beschleunigen, wurde das Rolling-Review-Verfahren eingesetzt, welches für solche pandemischen Gesundheitslagen etabliert wurde.…”

The journey of a lifetime — development of Pfizer’s COVID-19 vaccine

“…Usually, a traditional vaccine development process takes 10 years or more, but the pandemic required a much faster response 11 , 12 . With the support from leadership and leveraging Pfizer’s many years of vaccine development expertise, we took the educated risks to strategically perform activities in parallel that would normally occur sequentially in the traditional setting [13] .…”