Mastitis is the major problem for dairy farmers and - industry and Staphylococcus aureus (SA) being the most difficult causative pathogen often failing antibiotic treatment. Vaccine candidates have also failed because of low immunogenicity inducing no or low serum antibody and no antibody in milk. The outcome is often slaughter after a short production life and high economical losses counting150 to 200 $ cow & year for the farmer. We here present results with the 40 nm nanoparticle based on quillaja saponin (ISCOM matrix) that enhances potent immune responses to virus and bacteria. The 40 nm ISCOM particle enhanced potent immune responses to SA-bacterins and SA protein pathogenesis factors produced by rDNA technique including β-toxin, ClfA and FnBP both in blood and milk lasting over the experimental period or the whole lactation period. We have now a follow up with a 20 nm nanoparticle (G3) as an innovative carrier of the same active quillaja saponin component. G3 exhibits the same immune enhancing capacity as the ISCOM matrix particle with a superior robust production technique fulfilling the three cardinal criteria for adjuvants i.e. enhancement of efficacy, highly acceptable and affordable for animal use. Moreover, it is versatile adaptable for modification to meet various requirements for immune protection. Interestingly, the ISCOM formulation induces whey antibodies inhibiting internalization of SA bacteria in bovine mammary gland cells indicating the possibility of preventing persistent infection.