In this study, the association of the leptin gene (LEP), leptin receptor gene (LEPR), and the peroxisome proliferator activated receptor gamma gene (PPARG) using 11 single nucleotide polymorphisms to understand the humoral immune response to the influenza vaccine. The most common influenza vaccine is the trivalent inactivated influenza virus split containing two strains of flu antigens, A and B. These antigens promote the immune system to create protective antibodies to defend against activated influenza viruses. LEP is a gene that produces the protein leptin and regulates energy metabolism and immune response. Leptin is a protein hormone secreted by adipocytes. LEPR is the receptor on the immune cells and binds with leptin, which then regulates the proliferation and reactivity of T cells. PPARG coordinates with leptin, which plays a role in adipocyte differentiation and inflammatory response in protein interaction network. PPARG promotes recovery from the infection of influenza virus. The SNPs for all these genes were genotyped and their response to inactivated antigens were traced. The genes LEP and LEPR were the targeted genes for observation in their response to the antigens; however, the SNPs and immune response had no significant results. The PPARG had the most significant genotypic distribution with immune response to the antigens of the flu vaccine. The PPARG had a low responsiveness to the vaccine and LEPR only had low responsiveness in males and this could possibly due to women having higher concentrations of leptin. There were three SNPs seen in PPARG correlates with baseline levels of immunomodulator and vitamin D and these receptors interact with each other for the response to the influenza vaccine. The concentrations of leptin and the way receptors utilize this protein in response to flu antigens is the main influence of how these genes handle recovery and defense against antigens.