Protection against respiratory syncytial virus infection by DNA immunization

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Respiratory syncytial virus (RSV) causes significant infant and elderly morbidity/mortality.
• Past formalin-inactivated RSV vaccines were associated with enhanced lung pathology due to T helper cell type 2 (Th2) responses.
• Developing effective and safe RSV vaccines remains a critical challenge.

Purpose of the Study:

• To engineer and evaluate an optimized plasmid DNA vector expressing the RSV fusion (F) protein (DNA-F) for vaccination.
• To assess the immunogenicity and protective efficacy of DNA-F in a murine model.
• To investigate the capacity of DNA-F to modulate T helper cell responses.

Main Methods:

• Engineered an optimized DNA plasmid vector (DNA-F) encoding a secretory RSV F protein with rabbit beta-globin intron II.
• Administered DNA-F via intramuscular and intradermal routes in mice.
• Assessed neutralizing antibody, cytotoxic T lymphocyte, and Th1/Th2 responses post-vaccination and after RSV challenge.
• Measured protective efficacy and lung pathology.

Main Results:

• DNA-F induced potent neutralizing antibodies, cytotoxic T lymphocytes, and interferon gamma expression, comparable to live RSV.
• DNA-F immunization conferred protection against RSV infection.
• A DNA-F boost could shift pre-existing Th2 responses towards a Th1 profile.
• Route of administration modulated immune response: intramuscular led to balanced responses, while intradermal induced Th2 responses.

Conclusions:

• Optimized DNA-F immunization is a promising strategy for RSV vaccination.
• DNA-F elicits robust protective immunity and can modulate T helper cell responses.
• The DNA-F vaccine offers a potential alternative to existing strategies, addressing safety concerns associated with previous vaccines.