Prophylactic human papillomavirus (HPV) vaccines against cervical cancer were successfully developed; however, challenges such as high cost and low compliance still remain to be overcome. In addition, because many HPV types can cause cervical cancer, antigens of multiple HPV types are needed to achieve broad protection. In this study, a bivalent single-injection HPV vaccine was designed in which virus-like particles (VLPs) of HPV 16 L1 and HPV 18 L1 were used as antigens. A recently developed drug carrier that uses tannic acid/polyethylene glycol films as the erodible layer was employed to accomplish multiple pulsatile releases of the antigens. Monovalent single-injection vaccines for HPV 16 and HPV 18 were first designed. A bivalent single-injection vaccine was then obtained by simply mixing the two monovalent vaccines. The bivalent vaccine provided protection against both HPV types. More importantly, it elicited both humoral and cellular immune responses as potent as those elicited by the corresponding multiple dose vaccine because of their similar release profile of antigens. Cross-reactivity was observed between HPV 16 and 18 in terms of cellular immune responses, while no cross-reactivity was found in terms of humoral immune responses. Note that other multivalent single-injection vaccines could be designed in the same way. These vaccines are expected to help prevent cervical cancer because of their broad protection, enhanced compliance and lowered vaccination cost.
Single-injection vaccines may overcome issues, such as high cost and poor patient compliance, of the multi-bolus regimes dominantly used in vaccination. However no such vaccine has been commercialized because time-controlled release, an unconventional release kinetics, is difficult to achieve. Here a new time-controlled release system using dynamic layer-by-layer (LBL) film as erodible coating was used to design single-injection vaccine. Unlike commonly used degradable polymers, dynamic LBL film disintegrates at a constant rate, thus allowing distinct pulsatile release of antigen at predetermined intervals. The release pattern of the single-injection vaccine mimics closely to that of ordinary multi-dose regimes. It elicits both humoral and cellular immune responses which are comparable to or even stronger than the corresponding multi-dose regime. In addition, it inhibits tumor growth more effectively. The new vaccine will not only improve patient compliance but also therapeutic outcome.
Synthetic or natural materials have been used as vaccines in cancer immunotherapy. However, using them as vaccines necessitates multiple injections or surgical implantations. To tackle such daunting challenges, we develop an injectable macroporous Bombyx mori (B. mori) silk fibroin (SF) microsphere loaded with antigens and immune adjuvants to suppress established tumors with only a single injection. SF microspheres can serve as a scaffold by injection and avoid surgical injury as seen in traditional scaffold vaccines. The macroporous structure of the vaccine facilitates the recruitment of immune cells and promotes the activation of dendritic cells (DCs), resulting in a favorable immune microenvironment that further induces strong humoral and cellular immunity. We have also modified the vaccine into a booster version by simply allowing the antigens to be adsorbed onto the SF microspheres. The booster vaccine highly efficiently suppresses tumor growth by improving the cytotoxic T lymphocyte (CTL) response. In general, these results demonstrate that the macroporous SF microspheres can serve as a facile platform for tumor vaccine therapy in the future. Since the SF microspheres are also potential scaffolds for tissue regeneration, their use as a vaccine platform will enable their applications in eradicating tumors while regenerating healthy tissue to heal the tumor-site cavity.
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