Review of approaches to generating a mucosal (antibody) vaccine response targeted at the ruminal Archaea

Summary

The potential to reduce methane production from ruminants is of major interest in Australia and internationally. As well as reducing the greenhouse gas production from ruminants, reducing methane production in the rumen could potentially enhance productivity and feed efficiency, as methane losses account for about 6-10% of gross feed intake. Many approaches are being evaluated but with recent progress in vaccine development, it is appropriate to once more review the possibilities for an immunization approach. There are precedents for a vaccination approach in that there are reports where vaccination against specific rumen microbes was effective in preventing lactic acidosis in cattle and sheep. 
The review provides a survey of the literature and proposes a protocol for evaluation to induce a mucosal secretory IgA and IgG response. It is recognized that a reliable vaccine to lower methane emissions will need to target a wide array of methanogens and induce a mucosal, and potentially a systemic, response. The review assumes that appropriate target motifs are available (this area is the subject of a number of projects within CSIRO and in New Zealand). IgG is the predominant immunoglobulin class in serum, but the main immunoglobulin in bovine saliva is IgA and this is the effector group of the mucosal immune response. Since IgA antibodies, specifically secretory IgA (S-IgA), have a relatively high tolerance to proteolytic enzymes, they have a better chance of surviving in the ruminal environment and hence are the preferred target for a vaccination solution. 
The use of prime-boost vaccination regimes enhances the efficacy of vaccination. Since the methanogenic Archaea reside in the rumen without entering into the mucosa or affecting the mucosal surface (e.g. by inflammation), the vaccine must target the topical mucosal response via the salivary glands. However the salivary glands are not easily accessible and indeed vaccination requiring administration directly would not be practical at any scale. Evidence indicates that the main source of salivary IgA in ruminants is the sub-lingual gland. While the nasal cavity is a logical target for vaccination against respiratory diseases in ruminants, it is not the approach of choice to stimulate secretion of immunoglobulins in saliva. The preferred target is vaccination per the sub-lingual route. Considering that a keratinized oral mucosa is found in ruminants and rodents, findings in rodents should be readily transferrable to ruminants.