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Soluble recombinant human metapneumovirus G protein is immunogenic but not protective
Alex B Ryder1, Sharon J Tollefson, Amy B Podsiad
1Vanderbilt University Medical Center, School of Medicine, Nashville, TN 37232-2581, USA.
Abstract:
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 (GDeltaTM) that was secreted from mammalian cells and purified by affinity chromatography. We tested the immunogenicity of GDeltaTM in cotton rats. Animals were immunized with PBS, GDeltaTM alone or adjuvanted, or were infected once with HMPV, and challenged with live HMPV at 28 days. Animals vaccinated with adjuvanted and non-adjuvanted GDeltaTM 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.
Insights
Immunization with the G protein of human metapneumovirus (HMPV) generated antibodies but not protection. This suggests HMPV G is not a protective antigen, unlike similar proteins in other paramyxoviruses.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Human metapneumovirus (HMPV) is a significant respiratory pathogen.
- Surface glycoproteins F and G are key targets for immune responses.
- The protective role of HMPV G protein in immunity is not well understood.
Purpose of the Study:
- To evaluate the protective efficacy of immunization with the HMPV G protein.
- To assess the immunogenicity of a recombinant G ectodomain (GDeltaTM) in a relevant animal model.
Main Methods:
- A recombinant G ectodomain (GDeltaTM) was generated and purified.
- Cotton rats were immunized with GDeltaTM (alone or adjuvanted) or infected with HMPV.
- Animals were subsequently challenged with live HMPV to assess protection.
Main Results:
- Vaccination with GDeltaTM induced high antibody titers against both recombinant and native G protein.
- Despite antibody induction, vaccinated animals did not develop neutralizing antibodies.
- Vaccinated animals were not protected against live HMPV challenge.
Conclusions:
- HMPV G protein, unlike analogous glycoproteins in other human paramyxoviruses, does not appear to be a protective antigen.
- This finding highlights an unusual characteristic of HMPV.
- Further research into alternative HMPV vaccine targets, such as the F protein, is warranted.
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