The global strategy to control coronavirus disease is based on the availability of COVID-19 vaccines. More information about response to a single dose vaccine could help to better understand and optimize the management of the vaccine campaign. Workers from the University of Rome "Tor Vergata" and the University Hospital of University of Rome "Tor Vergata," were monitored during their vaccination program. Serum samples were collected between the first and second dose and after the second dose. University personnel has been vaccinated with two doses of Vaxzevria vaccine 12 weeks apart, while hospital personnel has been vaccinated with two doses of Cominarty 3 weeks apart. IgG antibodies (Abs) against the Receptor Binding Domain (RBD) of the virus spike surface glycoprotein and neutralizing antibodies (NT) anti-SARS-CoV-2 that block the interaction between RBD and the surface receptor cellular angiotensin converting enzyme (ACE2) were measured using the CL-series Mindray chemiluminescent assays, respectively. Different amounts of antibodies produced after the two doses of vaccine were found. Individuals with a previous natural infection developed a higher Abs titer. Among the individuals with no history of past SARS-CoV-2 infection, 5% had an Abs level of the same order of magnitude of infected people, suggesting that they acquired the infection in an asymptomatic way. In such individuals, one dose of vaccine may be sufficient to obtain a protective immune response.