In this thesis, we explore whether the protective efficacy of a trivalent virosomal seasonal influenza vaccine (TVV) can be broadened and thereby increase pandemic preparedness until more broadly protective influenza vaccines may become available.Chapter 2 examines the ability of a vaccination regimen comprising multiple immunizations to improve the cross-protective efficacy of TVV in mice.Chapter 3 explores whether priming a TVV with vaccine homologous HA DNA can improve its efficacy of inducing heterologous H1N1 and heterosubtypic H5N1 protection in mice. The cross-protective efficacy of the heterologous prime/boost regimen is evaluated in parallel with the multiple vaccination regimen identified in chapter 2.Chapter 4 investigates the ability of improving the cross-protective efficacy of TVV by adjuvating with Matrix M. The adjuvated vaccination regimen is evaluated for cross-protection against avian H5N1, H7N7 and H7N9 influenza viruses in both mice and ferrets. Leveraging two phase 1 clinical trials we in chapter 5-6 further evaluate the cross-reactivity and cross-protective efficacy of the humoral immune response elicited by seasonal and pandemic influenza vaccines in humans.Chapter 5 assesses the cross-protective efficacy of TVV in healthy adults. By making use of a novel human-to-mouse serum transfer and challenge model we evaluated the cross-protective efficacy of the humoral immune response induced by 1, 2 and 3x TVV in healthy adults.Chapter 6 further explores the role of ADCC in HA specific cross-reactivity and cross-protection induced by TVV and pandemic influenza vaccine in healthy adults.Chapter 7 comprises a summary and discussion of the findings presented in this thesis. The results are discussed in the context of the influenza vaccine field and the future perspective of broadly protective influenza vaccines.