Related Experiment Video
Updated: Sep 7, 2026
Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection
Published on: May 2, 2011
Development of safe and effective RSV vaccine by modified CD4 epitope in G protein core fragment (Gcf)
In Su Cheon1, Byoung-Shik Shim2, Sung-Moo Park3
1Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; World Class University Biomodulation Major and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
Insights
Developing a safe and effective Respiratory Syncytial Virus (RSV) vaccine is crucial. Researchers modified the RSV G protein core fragment (Gcf) to alter a CD4+ T cell epitope, successfully preventing vaccine-enhanced disease while maintaining protection against RSV infection.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Respiratory Syncytial Virus (RSV) causes significant respiratory illness in young children globally, with no current vaccine.
- The RSV G glycoprotein (RSVG) is a key target for immune responses, but a specific CD4+ T cell epitope is linked to harmful pulmonary eosinophilia.
- Existing vaccine strategies face challenges due to potential vaccine-enhanced disease.
Purpose of the Study:
- To engineer safe and effective RSV vaccines using modified RSV G protein core fragments (Gcf).
- To investigate the impact of altering the CD4+ T cell epitope on vaccine-induced immunity and safety.
- To develop a mucosal RSV vaccine strategy that avoids vaccine-enhanced disease.
Main Methods:
- Constructed several Gcf variants with modifications to the CD4+ T cell epitope.
- Immunized mice with Gcf variants and measured RSV-specific serum IgG levels.
- Assessed lung viral titers, pulmonary eosinophilia, and body weight changes post-RSV challenge.
Main Results:
- Wild-type Gcf from RSV A induced protective responses but also vaccine-enhanced disease.
- A modified Gcf (Th-mGcf) elicited strong RSV-specific IgG responses and protected against RSV A and partially against RSV B.
- Crucially, Th-mGcf immunization prevented vaccine-enhanced disease, including pulmonary eosinophilia.
Conclusions:
- Modifying the CD4+ T cell epitope within the RSV G protein is a viable strategy for developing safe RSV vaccines.
- The Th-mGcf variant demonstrates potential as a safe and effective mucosal RSV vaccine candidate.
- This approach offers a novel pathway to overcome vaccine-enhanced disease in RSV vaccine development.
Abstract:
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in infants and young children worldwide, but currently no safe and effective vaccine is available. The RSV G glycoprotein (RSVG), a major attachment protein, is an important target for the induction of protective immune responses during RSV infection. However, it has been thought that a CD4+ T cell epitope (a.a. 183-195) within RSVG is associated with pathogenic pulmonary eosinophilia. To develop safe and effective RSV vaccine using RSV G protein core fragment (Gcf), several Gcf variants resulting from modification to CD4+ T cell epitope were constructed. Mice were immunized with each variant Gcf, and the levels of RSV-specific serum IgG were measured. At day 4 post-challenge with RSV subtype A or B, lung viral titers and pulmonary eosinophilia were determined and changes in body weight were monitored. With wild type Gcf derived from RSV A2 (wtAGcf), although RSV A subtype-specific immune responses were induced, vaccine-enhanced disease characterized by excessive pulmonary eosinophil recruitment and body weight loss were evident, whereas wtGcf from RSV B1 (wtBGcf) induced RSV B subtype-specific immune responses without the signs of vaccine-enhanced disease. Mice immunized with Th-mGcf, a fusion protein consisting CD4+ T cell epitope from RSV F (F51-66) conjugated to mGcf that contains alanine substitutions at a.a. position 185 and 188, showed higher levels of RSV-specific IgG response than mice immunized with mGcf. Both wtAGcf and Th-mGcf provided complete protection against RSV A2 and partial protection against RSV B. Importantly, mice immunized with Th-mGcf did not develop vaccine-enhanced disease following RSV challenge. Immunization of Th-mGcf provided protection against RSV infection without the symptom of vaccine-enhanced disease. Our study provides a novel strategy to develop a safe and effective mucosal RSV vaccine by manipulating the CD4+ T cell epitope within RSV G protein.
