<p>In December 2019, a pneumonia epidemic was first reported in Wuhan, China. Soon after, its causal virus, a novel coronavirus or SARS‒CoV‒2, spread worldwide. The WHO officially declared the global COVID‒19 pandemic on March 11, 2020. Due to the pandemic and related increased medical treatment needs, not only the treatment for COVID‒19 but also for other diseases was brought into crisis, collapsing the overall medical system and causing devastating effects on people's health worldwide. Accordingly, the development of vaccines against SARS‒CoV‒2 became imperative. </p><p>While the EU and the US have actively promoted their vaccination policies, Japan has fallen behind due to pre-COVID accidents caused by vaccines, and lawsuits over inoculation. Thus it was thought there would be challenges regarding the conduction of new vaccine trials in Japan. Below is a list of some of the challenges we faced during our COVID‒19 vaccine studies:</p><p> ・Substantial time was needed to conduct ascending dose studies in which the safety in a low dose group must be confirmed before proceeding with a high dose group;</p><p> ・Due to accelerated public vaccinations, the recruitment of treatment-naïve subjects became increasingly diffi cult;</p><p> ・In some cases, subjects who had previously participated in a vaccine trial and received a study vaccine were not allowed to receive public vaccinations because the influence of the study vaccine on the safety and efficacy of approved vaccines was unknown.</p><p>As vaccinations have been recommended and new mutant strains reported, close attention to the development trends of new vaccines against the novel coronavirus variants remain important.</p>