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A Built-In CpG Adjuvant in RSV F Protein DNA Vaccine Drives a Th1 Polarized and Enhanced Protective Immune Response
Yao Ma1,2, Yue-Ying Jiao3, Yun-Zhou Yu4
1College of Life Sciences & Bioengineering, Beijing Jiaotong University, Beijing 100044, China. 13118422@bjtu.edu.cn.
Insights
CpG-C motifs enhance DNA vaccines against respiratory syncytial virus (RSV). This adjuvant improved antibody and T-cell responses, reducing lung disease and virus replication in mice, suggesting a promising RSV vaccine strategy.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Human respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children.
- Currently, no licensed vaccine is available for RSV prevention.
Purpose of the Study:
- To investigate the adjuvant effect of C-Class CpG oligodeoxynucleotides (CpG-C) on a plasmid DNA vaccine encoding the RSV fusion (F) glycoprotein.
- To evaluate the impact of CpG-C incorporation on vaccine-induced immune responses and protection against RSV challenge.
Main Methods:
- Plasmid DNA vaccines encoding RSV F glycoprotein were constructed with either five or 20 copies of CpG-C motifs.
- BALB/c mice were immunized with these DNA vaccines, followed by RSV challenge.
- Humoral (antibody) and cellular (T-cell) immune responses, as well as pulmonary pathology and virus replication, were assessed.
Main Results:
- CpG-C motif incorporation significantly enhanced serum binding and virus-neutralizing antibody titers.
- Vaccination with CpG-modified DNA vaccines, particularly the 20-copy version, promoted a Th1-biased immune response.
- CpG-modified vaccines reduced pulmonary pathology, viral replication, and weight loss following RSV challenge.
Conclusions:
- CpG-C motifs act as effective built-in adjuvants in DNA vaccines targeting the RSV F glycoprotein.
- This strategy significantly improves vaccine efficacy against RSV infection by modulating immune responses and conferring protection.
Abstract:
Human respiratory syncytial virus (RSV) is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C) motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F) glycoprotein on the vaccine-induced immune response. The addition of CpG-C motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c mice immunized with the DNA vaccines. Moreover, mice vaccinated with CpG-modified vaccines, especially with the higher 20 copies, resulted in an enhanced shift toward a Th1-biased antibody and T-cell response, a decrease in pulmonary pathology and virus replication, and a decrease in weight loss after RSV challenge. This study suggests that CpG-C motif, cloned into the backbone of DNA vaccine encoding RSV F glycoprotein, functions as a built-in adjuvant capable of improving the efficacy of DNA vaccine against RSV infection.
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