COVID-19 vaccinations have significantly controlled the pandemic. To elucidate their impact on the immune system, we developed a COVID-19 vaccination atlas through an integrative systems vaccinology approach. Our atlas includes both healthy individuals and those infected with or without prior vaccination, and covers the administration of five vaccines in different regimens: Covilo®, Zifivax®, Vaxzebria® or Covishield®, Spikevax®, and Comirnaty®. We identified critical markers to discriminate the various types of vaccines and infection, in which infection was associated with GATA3, ZNF3, KMT2A, ASXL1, SP100, and GZMM, and vaccine types were marked by ITGAM, ACTG1, LGALS3, and STAT5B. Additionally, we described the immunological signatures resulting from heterologous vaccination and infection, and also showed how a full vaccination regimen markedly limited the shift of immune responses during natural infection, thereby constraining disease progression. Finally, we described the common transcripts shared across COVID-19 vaccines and vaccines against other pathogens.