Functionally diversified layered dissolving microneedles (FDMN) for highly concentrated live bacillus Calmette-Guerin (BCG) vaccine delivery

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a critical global health concern despite the availability of preventive measures such as the bacillus Calmette-Guerin (BCG) vaccine. While BCG vaccination is typically administered intradermally (ID) or percutaneously (PC), these methods pose challenges, including pain, scarring, and difficulties in administration, particularly in infants and children. Microneedle (MN) delivery has emerged as a promising alternative, offering painless delivery, minimal invasiveness, enhanced immune response, and dose-saving benefits. In this study, a functionally diversified layered dissolving MN loaded with highly concentrated live BCG (FDMN), capable of delivering a viable immunogenic dose exceeding 3 x 105 CFUs transdermally, has been developed. Its layered design ensures the preservation of BCG vaccine activity, facilitating effective vaccination against TB. A vaccination-challenge study conducted in C57BL/ 6 mice demonstrated that the FDMN offers comparable protective efficacy to conventional BCG vaccination, with reduced pain, minimal scarring, and the potential for self-administration. These findings highlight the potential of FDMN as a novel, patient-friendly approach for BCG vaccination in human, addressing many limitations of current methods.