The present invention provides methods of vaccination as well as pharmaceutical combinations and kits for enhancing vaccine effectiveness, including for immunodeficient or immunecompromised patients, including non-responders and low-responders to vaccination. As disclosed herein, the invention relates to administering a vaccine and a regimen of thymosin alpha peptide so as to provide higher antibody titers, speed the development of such antibody titers, and/or to provide for a longer duration of such antibody titers, thereby providing a greater protective effect. In another aspect, the invention allows for reducing a vaccine dose, such as an influenza vaccine dose, by administration of a thymosin peptide regimen.