The invention is a novel chemical coupling methodology for the synthesis of a stable polysaccharide-protein conjugates as the immunogenic component for vaccines. A covalent bond is formed between polysaccharide and protein in the dry state in the absence of water and oxygen. A polysaccharide antigen is covalently linked to the protein by activating the polysaccharide with periodate to introduce aldehyde groups into the polysaccharide, lyophilizing an aqueous mixture of a protein and activated polysaccharide, sealing the dry lyophilized mixture in a vessel under vacuum or inert gas and then incubating the sealed vessel at an elevated temperature.
