Transcutaneous immunization of recombinant Staphylococcal enterotoxin B protein using a dissolving microneedle provides potent protection against lethal enterotoxin challenge

Vaccine. 2019 Jun 27;37(29):3810-3819. doi: 10.1016/j.vaccine.2019.05.055. Epub 2019 May 27.

Abstract

Staphylococcal enterotoxin B (SEB) produced by the Staphylococcus aureus bacteriumis most commonly associated with food poisoning and is known to also cause toxic shock syndrome. Currently, no approved vaccine or specific drug is available to treat SEB intoxication. In this study, we fabricated dissolving microneedles (MNs) loaded with recombinant SEB (rSEB) protein, and evaluated its characteristics, including dissolution profile, protein particle size, insertion depth, antigen retention time in vivo, and skin irritation. Our results showed that rSEB protein-loaded dissolving MNs made of chondroitin sulfate (2%) and trehalose (0.8%) could easily penetrate into the mouse skin within 5 min. The rSEB particle size was unchanged before and after MN fabrication. The skin penetration depth of the MNs was 260 µm. Moreover, the MNs also significantly extended the antigen retention time in vivo. rSEB protein-loaded dissolving MNs also triggered slight erythema at the beginning of administration, but this erythema disappeared within a few hours. More importantly, we investigated the immunogenicity and protective efficacy of rSEB protein-loaded dissolving MNs. Challenge studies in mice revealed that mice in full-dose MN group had a high level of SEB specific antibody response thatprovided100% protection against a lethal SEB toxin challenge. However, there was only 60% protection observed in mice that were in the half-dose MN (dose sparing) group. We also determined the pathological alterations in the tissues of the immunized mice. Taken together, these dissolving MNs may present a promising transcutaneous immunization strategy for treating SEB intoxication.

Keywords: Dissolving microneedle; Transcutaneous immunization; rSEB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Antibodies, Bacterial / blood
  • Enterotoxins / administration & dosage*
  • Enterotoxins / genetics
  • Enterotoxins / immunology
  • Female
  • Immunization / methods*
  • Mice
  • Mice, Inbred BALB C
  • Microinjections / instrumentation*
  • Needles*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Skin / drug effects
  • Skin / pathology
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcus aureus
  • Swine

Substances

  • Antibodies, Bacterial
  • Enterotoxins
  • Recombinant Proteins
  • enterotoxin B, staphylococcal