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Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
Plasmid DNA encoding the respiratory syncytial virus G protein is a promising vaccine candidate
X Li1, S Sambhara, C X Li
1Research Center, Pasteur Mérieux Connaught Canada, 1755 Steeles Avenue West, North York, Ontario, M2R 3T4, Canada.
Insights
New DNA-G vaccines show promise for preventing respiratory syncytial virus (RSV) by eliciting balanced immune responses without causing harmful lung inflammation in animal models, unlike older vaccine approaches.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Respiratory syncytial virus (RSV) is a significant cause of severe respiratory illness in vulnerable populations.
- Past RSV vaccine development faced setbacks, notably enhanced lung disease in infants from formalin-inactivated vaccines.
- Previous research linked enhanced lung pathology to Th2 immune responses against the RSV G protein.
Purpose of the Study:
- To evaluate DNA-G vaccination for its ability to induce balanced immune responses against RSV.
- To assess the safety and efficacy of DNA-G immunization in preventing RSV-induced lung disease.
Main Methods:
- Vaccination of mice and cotton rats with plasmid vectors encoding full-length or secreted G protein (DNA-G).
- Assessment of systemic and pulmonary cytokine responses (Th1/Th2 balance).
- Evaluation of pulmonary inflammatory reactions post-RSV challenge.
- Measurement of virus-neutralizing antibody titers and protection against lower respiratory tract infection.
Main Results:
- DNA-G vaccination induced balanced Th1/Th2 cytokine responses in mice.
- No atypical pulmonary inflammation was observed in cotton rats after RSV challenge.
- Significant virus-neutralizing antibody responses were generated.
- Effective protection against RSV lower respiratory tract infection in both species.
Conclusions:
- DNA-G immunization elicits a balanced immune response, similar to live RSV infection.
- DNA-G is a safe and effective immunogen, demonstrating potential for a nucleic acid-based RSV vaccine.
- This approach overcomes previous safety concerns associated with RSV vaccine development.
Abstract:
Respiratory syncytial virus (RSV) remains a major cause of severe respiratory diseases in infants, young children, and the elderly. However, development of a RSV vaccine has been hampered by the outcome of the infant trials in the 1960s with a formalin-inactivated RSV preparation. Enhanced lung disease was induced by the vaccination post-RSV exposure. Previous studies in mice primed with RSV G protein either formulated in adjuvants or delivered by recombinant vaccinia viruses have indicated that enhanced lung pathology resulted from a Th2-type host immune response against the viral G protein. However, in the present report, we have demonstrated that vaccination with plasmid vectors encoding either a full-length or a secreted G protein (DNA-G) clearly elicited balanced systemic and pulmonary Th1/Th2 cytokine responses in mice and did not induce an atypical pulmonary inflammatory reaction post-RSV challenge in cotton rats. DNA-G immunization also induced marked virus neutralizing antibody responses and protection against RSV infection of the lower respiratory tract of both mice and cotton rats. So far, only genetic immunization has been able to induce a balanced Th1/Th2 response with the RSV G protein, reminiscent of that induced by live RSV. Therefore, DNA-G is a promising immunogen for inclusion in a nucleic acid RSV vaccine.
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