Abstract
Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×108 copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×109 copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×1010 copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×109 copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.
Highlights
Needle-free vaccination via mucosal routes has drawn increasing recent attention as a vaccine delivery strategy
AcHERV-triHPV was detected in blood, thymus, cervical lymph node, spleen, liver, lung, kidney, brain, and heart at 15 minutes post-dose
Sublingually administered AcHERV-triHPV showed a higher distribution to the lungs compared to other tissues at 15 minutes and 1 hour after administration, but did not persist in the lung for more than 24 hours
Summary
Needle-free vaccination via mucosal routes has drawn increasing recent attention as a vaccine delivery strategy. Sublingual HPV DNA Vaccine in Baculovirus induction of pathogen-specific memory immune responses at the appropriate mucosal compartment, thereby preventing the entry and/or replication of the invading pathogen at the site of infection [1]. Buccal, or sublingual routes have recently emerged as alternatives to intramuscular (IM) vaccine administration. Non-parenteral, needlefree mucosal vaccination has several advantages, including reduced pain stresses, costs, and viral transmission associated with the injection [2,3]. A number of studies have explored the potential of SL immunization in eliciting desired immune responses against various potential vaccine components, including protein antigens [6,7], and live-attenuated viruses [8,9]. Few studies have investigated SL delivery of DNA vaccines using viral vectors
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