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Pharmaceutical and Immunological Evaluation of Cholera Toxin A1 Subunit as an Adjuvant of Hepatitis B Vaccine Microneedles

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Abstract

Purpose

For successful delivery of a solid vaccine formulation into the skin using microneedles, the solubility of an adjuvant should be considered because the decrease in the dissolution rate by the addition of adjuvant decreases the delivery efficiency of the vaccine.

Methods

In this study, cholera toxin A subunit 1 (CTA1) was examined as an adjuvant to Hepatitis B vaccine (HBV) microneedles because of its good water solubility, improved safety, and positive effect as shown in intramuscular administration of a liquid vaccine.

Results

All solid formulations with CTA 1 dissolved in in vivo mouse skin within 30 min, and they were successfully delivered into the skin. In experiments with mice, the addition of CTA1 led to improved IgG immune response compared to the use of an aluminum hydroxide–based formulation and intramuscular administration of HBV. In addition, CTA1 induced CD8 + T cell response as much as in which the aluminum hydroxide–based formulation induced.

Conclusions

CTA1 is an adjuvant that satisfies both the delivery efficiency and the immunological characteristics required for vaccine microneedles. CTA1 will be used as a potential adjuvant through vaccine microneedles.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

Alum:

Aluminum hydroxide

CT:

Cholera toxin

CTA1:

Cholera toxin A subunit 1

HBV microneedle:

Hepatitis B vaccine microneedle

HBsAg:

Hepatitis B surface antigen

HA:

Hyaluronic acid

HBsAg-microneedles:

Microneedles coated with a formulation of HBsAg only

HBsAg-Alum-microneedles:

Microneedles coated with a formulation of HBsAg and Alum

HBsAg-CTA1-microneedles:

Microneedles coated with a formulation of HBsAg and CTA1

HRP:

Horseradish peroxidase

ELISA:

Enzyme-linked immunosorbent assay

ELISpot:

Enzyme-linked immunosorbent spot

OD:

Optical density

SDS-PAGE:

Sodium dodecyl sulphate–polyacrylamide gel electrophoresis

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Funding

This work was supported by National Research Foundation of Korea (NRF) grants funded by Korea Ministry of Trade, Industry & Energy (MOTIE, 20014911 (Industrial Strategic Technology Development Program)), by Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HV22C0029).

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Author notes

  1. Jong-Chan Kim and Jung-ah Choi is contributed equally to this work.

Authors and Affiliations

  1. Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam, South Korea

    Jong-Chan Kim, Ji-Seok Kim, Moon-Jin Kim & Jung-Hwan Park

  2. Science Unit, International Vaccine Institute, Seoul, South Korea

    Jung-ah Choi, Hayan Park, Eunji Yang, Shinyoung Noh & Manki Song

Authors
  1. Jong-Chan Kim
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  2. Jung-ah Choi
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Contributions

Conceptualization: P.J., H.H.; Methodology & Investigation: K.G, S.G., P.J., J.W.; Software: M.J and G.W, K.J; Formal Analysis: B.S.; Writing & Draft Preparation: K.J., P.J., H.H.; Writing-review& Editing: all authors; Supervision: P.J., H.H.; Funding Acquisition: B.S., H.H. Data curation: H.H., P.J., P.J.

Corresponding authors

Correspondence to Manki Song or Jung-Hwan Park.

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Conflict of Interest

PJH is an inventor of patents that have been licensed to companies developing microneedle-based products, is a shareholder of companies developing microneedle-based products.

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Kim, JC., Choi, Ja., Park, H. et al. Pharmaceutical and Immunological Evaluation of Cholera Toxin A1 Subunit as an Adjuvant of Hepatitis B Vaccine Microneedles. Pharm Res 40, 3059–3071 (2023). https://doi.org/10.1007/s11095-023-03623-9

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