Vaccines are the most powerful pharmaceutical tool to combat the COVID-19 pandemic. While the majority (about 65%) of the German population were fully vaccinated, incidence started growing exponentially in October 2021 with about 41% of recorded new cases aged twelve or above being symptomatic breakthrough infections, presumably also contributing to the dynamics. At the time, it (i) remains elusive how significant this contribution is and (ii) whether targeted non-pharmaceutical interventions (NPIs) may stop the amplification of the ongoing crisis. Here, we estimate that about 67%–76% of all new infections are caused by unvaccinated individuals, implying that only 24%–33% are caused by the vaccinated. Furthermore, we estimate 38%–51% of new infections to be caused by unvaccinated individuals infecting other unvaccinated individuals. In total, unvaccinated individuals are expected to be involved in 8–9 of 10 new infections. We further show that decreas- ing the transmissibility of the unvaccinated by, e. g. targeted NPIs, causes a steeper decrease in the effective reproduction number R than decreasing the transmissibility of vaccinated individuals, potentially leading to temporary epidemic control. Furthermore, reducing contacts between vaccinated and unvaccinated individuals serves to decrease R in a similar manner as increasing vaccine uptake. Taken together, our results contribute to the public discourse regarding policy changes in pandemic response and highlight the importance of combined measures, such as vaccination campaigns and contact reduction, to achieve epidemic control and preventing an overload of public health systems.