Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation

Area of Science:

• Vaccinology
• Molecular Biology
• Immunology

Background:

• Naked DNA vaccines offer manufacturing simplicity and stability.
• Improved delivery methods are crucial for enhancing DNA vaccine immunogenicity.
• Human papillomavirus (HPV) vaccines aim to prevent HPV-related diseases.

Purpose of the Study:

• To evaluate in vivo electroporation as a delivery technology for multivalent codon-optimized human papillomavirus (HPV) L1 and L2 DNA vaccination.
• To compare the immunogenicity of HPV DNA vaccines delivered by electroporation, intramuscular injection, and gene gun.
• To investigate the impact of co-administered L1 and L2 constructs and multivalent formulations on immune responses.

Main Methods:

• Balb/c mice received three vaccinations with HPV L1/L2 DNA constructs or fusion proteins.
• Vaccine delivery methods included in vivo electroporation, intramuscular injection, and gene gun.
• Humoral immune responses were assessed by in vitro neutralization titers and passive protection assays.
• In vitro studies examined heterotypic interactions between HPV L1 proteins.

Main Results:

• In vivo electroporation of HPV L1 DNA induced strong, type-restricted neutralizing antibodies, comparable to Gardasil.
• Electroporation demonstrated superior immunogenicity over intramuscular injection and gene gun delivery.
• Co-expression of L2 did not enhance L1-specific responses or induce L2 antibodies.
• Multivalent HPV L1 DNA vaccination resulted in reduced antibody titers due to L1 protein interactions, which could be mitigated by spatial separation or L2 co-expression.

Conclusions:

• In vivo electroporation is an effective delivery method for HPV L1 DNA vaccines.
• Spatial separation of individual type L1 DNA vaccines is essential for successful multivalent HPV vaccination using electroporation.
• Further optimization of multivalent DNA vaccine formulations is needed to overcome heterotypic interference.