COVID-19 vaccines: An ongoing race

Worldwide, several hundred COVID-19 vaccine candidates are currently under investigation; some of them already in phase 3 trials. Hopefully approved as of 2021, vaccines may help to fight the COVID-19 pandemic [1].

The development of vaccines differs somewhat from drug development: study participants are healthy volunteers, and the number of participants may be as high as 60,000 in phase 3 testing. Main primary outcomes are safety, tolerability and, especially in phase 3 trials, immunogenicity. The different types of vaccines currently being developed include DNA- or mRNA-based technologies, attenuated or inactivated viruses, virus-like particles as well as replicating and non-replicating viral vectors expressing SARS-CoV-2 proteins.

“Both the number and the procedures towards a development of an effective vaccine for COVID-19 are unprecedented,” stated Prof. George Karakiulakis (Aristotle University of Thessaloniki, Greece). A recent review from September 2020, counted 321 vaccine candidates in various stages of development globally [2]. Some 143 are in preclinical and 33 in clinical stages of development. Of the candidates in clinical trials, 10 are currently in phase 1, 15 in phase 1/2 or 2, and 8 are already in phase 3 clinical evaluations [1].

Most of the vaccine candidates in phase 1 have a dose regimen of 2 doses 3-4 weeks apart and they are given intramuscularly. Among those in phase 2, one will be given intradermally. “Our hope is on the 8 vaccines in phase 3,” said Prof. Karakiulakis (see Table) [1]. Some of those trials received early permissions to move on to phase 3 after preliminary favourable results and before the planned ending of earlier phases. The time frames for phase 3 study completion according to the different protocols range from May 2021 to October 2022. There have also been 3 announcements of early vaccinations that raised concerns. One of those, from the Gamaleya Research Institute (Russia), has only published results from phase 1 but no results from phase 2 or 3. Nevertheless, Russia is preparing for mass vaccination to start in October 2020. Similarly, China announced inoculation of candidate vaccines without publicly known results from a phase 3 trial to the military and medical workers as of July 2020.

Normally, the Food and Drug Administration in the USA has strict rules for vaccines, which state that a vaccine should reduce the rate of symptomatic disease by 50% and there should be safety data of ≥1 year for ≥3,000 patients. Yet, currently, there is pressure on the FDA to approve a vacinne by 1 November 2020. “Experts think that the FDA may grant an emergency use authorisation rather than full approval,” Prof. Karakiulakis pointed out. Aaccording to Dr Anthony S. Fauci, director of the NIAID and US Government’s infecious disease expert, a vaccine for widespread use will likely not be available before March to September 2021.

Table: COVID-19 vaccines that are in phase 3 studies [1]



 

1. 
   
   1. Karakiulakis G. Vaccines - Early clinical trials. COV3620, ERS International Virtual Congress 2020, 7-9 Sept.
   2. Le TT, et al. Nat Rev Drug Discov. 2020;19:667-668.

Posted on 29 October 202029 February 2024