The impact of host genetic variation in shaping innate and adaptive immune responses is an emerging lever to consider in new vaccination strategies. This issue has been addressed by the H2020-funded SAPHIR project by studying the genetic control of responses to vaccines against Mycoplasma hyopneumoniae (M. hyo) or Influenza A Virus (IAV) in pigs. Large White pigs housed in a conventional facility (48 families produced in five batches) were vaccinated at weaning (around 28 days of age), which was followed with a booster vaccination three weeks later. Overall, 182 and 98 piglets were vaccinated against M. hyo or IAV, respectively, and 64 non-vaccinated piglets were included as shared controls for the two vaccine experiments. The humoral vaccine response was measured by following the dynamics of seric M. hyo- or IAV-specific IgG, prior vaccination on the vaccine day, every week during five weeks post-vaccination, and before slaughtering at 21 weeks-of-age. In addition, haemagglutination inihibition (HAI) assays were performed for IAV-vaccinated pigs. Our results showed a wide range of individual variability. One week after the booster vaccination, M. hyo IgG levels (relative to a positive control) ranged from 0.36 to 2.15 (mean=1.34, coefficient of variation=21.2%) and IAV-specific IgG levels ranged from 10.3 to 128.5 µg/mL (mean=33.41 µg/mL, coefficient of variation=69.6%). For IAV-vaccinated animals, HAI titers ranged from 40 to 2560 (geometric mean=343.7). Interestingly, females exhibited a significantly higher humoral immune response to vaccination compared to males for the two vaccines. Heritability of specific antibody response variation could be estimated for animals vaccinated against M. hyo (h2=0.34 one week after the booster vaccination), showing a moderate genetic control. Ongoing genome wide association studies (GWAS) have revealed few candidate genomic regions found associated with the individual variability of vaccine responses to M. hyo or IAV that need to be further investigated.