Abstract
BackgroundZinc oxide nanoparticle (ZNP) has been applied in various biomedical fields. Here, we investigated the usage of ZNP as an antigen carrier for vaccine development by combining a high affinity peptide to ZNP.ResultsA novel zinc oxide-binding peptide (ZBP), FPYPGGDA, with high affinity to ZNP (K a = 2.26 × 106 M−1) was isolated from a random peptide library and fused with a bacterial antigen, ScaA of Orientia tsutsugamushi, the causative agent of scrub typhus. The ZNP/ZBP-ScaA complex was efficiently phagocytosed by a dendritic cell line, DC2.4, in vitro and significantly enhanced anti-ScaA antibody responses in vivo compared to control groups. In addition, immunization with the ZNP/ZBP-ScaA complex promoted the generation of IFN-γ-secreting T cells in an antigen-dependent manner. Finally, we observed that ZNP/ZBP-ScaA immunization provided protective immunity against lethal challenge of O. tsutsugamushi, indicating that ZNP can be used as a potent adjuvant when complexed with ZBP-conjugated antigen.ConclusionsZNPs possess good adjuvant potential as a vaccine carrier when combined with an antigen having a high affinity to ZNP. When complexed with ZBP-ScaA antigen, ZNPs could induce strong antibody responses as well as protective immunity against lethal challenges of O. tsutsugamushi. Therefore, application of ZNPs combined with a specific soluble antigen could be a promising strategy as a novel vaccine carrier system.
Highlights
IntroductionWe investigated the usage of Zinc oxide nanoparticle (ZNP) as an antigen carrier for vaccine development by combining a high affinity peptide to ZNP
Zinc oxide nanoparticle (ZNP) has been applied in various biomedical fields
Our results showed that immunization with ZNP/zinc oxide-binding peptide (ZBP)-ScaA complexes induced proper adaptive immune responses and could provide comparable protection against lethal challenges of O. tsutsugamushi as a conventional vaccine adjuvant, alum hydroxide, suggesting that ZNPs may potentially be used as an antigen carrier and adjuvant system when combined with ZBP-conjugated antigens
Summary
We investigated the usage of ZNP as an antigen carrier for vaccine development by combining a high affinity peptide to ZNP. ZNPs exposure might induce strong local inflammation at the injection site [17] and this can be linked to the generation of antigen-specific adaptive immune responses, including antibodies as well as T cell responses, when combined with a specific protein antigen [18]. Even though the detailed immunological mechanisms of how ZNPs stimulate the immune system and contribute to the generation of specific immunity against co-injected antigen need to be investigated [19], it is intriguing to observe that inflammatory responses induced by injection of ZNPs are linked to augmentation of antigen-specific adaptive immunity
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