Methane produced by domestic livestock is responsible for 30% of anthropogenic greenhouse gas emissions in New Zealand. Our approach to mitigation of methane is to vaccinate sheep and cattle to induce a strong and sustained salivary antibody response that delivers anti-methanogen antibodies into the rumen. These antibodies would interact with protein antigens on the surface of ruminal methanogens and inhibit their ability to produce methane. An effective vaccination strategy will need to produce high levels of antibody in the saliva and the type of adjuvant used to formulate vaccine antigens, route of vaccination and stability of salivary antibody in the rumen are critical for success of a vaccine. Trials were conducted in sheep and cattle using the cell wall biosynthesis glycosyl transferase GT2 from Methanobrevibacter ruminantium M1 as a model antigen. Groups (n=6) of sheep were vaccinated twice by the subcutaneous route with recombinant GT2 (rGT2) formulated with Montanide ISA61, saponin, a chitosan thermogel, or a lipid nanoparticle/cationic liposome adjuvant. GT2-specific antibody responses in sera and saliva were measured by ELISA. Montanide ISA61 was shown to be the most effective adjuvant at inducing GT2-specific antibodies in saliva, with predominately IgG produced. This adjuvant was also effective in cattle vaccinated with rGT2. In that trial, addition of the TLR4 agonist, monophosphoryl lipid A to the Montanide ISA61 did not result in higher antibody titres compared to Montanide ISA61 alone. Using an in vitro assay which simulated conditions in the rumen environment, antigen-specific antibodies in the saliva from ruminants were shown to be relatively stable in the rumen. From the levels of salivary antibodies, it was calculated that parenteral vaccination of ruminants could produce sufficient numbers of molecules of antigen-specific IgG to effectively target all methanogen cells resident in the rumen. These studies suggest the feasibility of a vaccination-based mitigation strategy for livestock generated methane.