Soluble recombinant human metapneumovirus G protein is immunogenic but not protective

Human metapneumovirus (HMPV) expresses the major surface glycoproteins F and G. We evaluated the protective efficacy of immunization with G. We generated a recombinant form of G ectodomain (GΔTM) that was secreted from mammalian cells and purified by affinity chromatography. We tested the immunogenicity of GΔTM in cotton rats. Animals were immunized with PBS, GΔTM alone or adjuvanted, or were infected once with HMPV, and challenged with live HMPV at 28 days. Animals vaccinated with adjuvanted and non-adjuvanted GΔTM developed high levels of serum antibodies to both recombinant and native G protein; however, vaccinated animals did not develop neutralizing antibodies and were not protected against virus challenge. Unlike the analogous non-fusion glycoproteins of other human paramyxoviruses, HMPV G does not appear to be a protective antigen. This represents an unusual feature of HMPV.