Enhancing influenza vaccine immunogenicity and efficacy through infection mimicry using silk microneedles

• Published in: Vaccine 2021-09, Vol.39 (38), p.5410-5421
• Main Authors: Stinson, Jordan A., Boopathy, Archana V., Cieslewicz, Brian M., Zhang, Yichen, Hartman, Nickolas W., Miller, David P., Dirckx, Matthew, Hurst, Brett L., Tarbet, E. Bart, Kluge, Jonathan A., Kosuda, Kathryn M.
• Format: Article
• Language: English
• Subjects: Animal models; Antibodies; Antigens; Controlled release; Dermis; Disease control; Immune clearance; Immune response; Immunization; Immunogenicity; Infection mimicry; Infections; Influenza; Influenza vaccine; Kinetics; Laboratory animals; Lymphatic system; Lymphoid tissue; Microneedle; Mimicry; Needles; Seroconversion; Silk; Silk fibroin; Skin; Sustained release; Vaccines; Viruses
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2021.07.064

•Infection mimicry enhances humoral and cellular immune responses to flu vaccine.•Silk microneedle patches achieve influenza vaccine release for 2 weeks in mice.•Immunization with MIMIX patches promotes stronger and more durable HAI titers.•Sustained vaccine release leads to higher HAI titers against drifted flu strains.•MIMIX vaccination improves protection against lethal influenza challenge in mice. Traditional bolus vaccine administration leads to rapid clearance of vaccine from lymphoid tissue. However, there is increasing evidence suggesting that the kinetics of antigen delivery can impact immune responses to vaccines, particularly when tailored to mimic natural infections. Here, we present the specific enhancements sustained release immunization confers to seasonal influenza vaccine, including the magnitude, durability, and breadth of humoral responses. To achieve sustained vaccine delivery kinetics, we have developed a microneedle array patch (MIMIX), with silk fibroin-formulated vaccine tips designed to embed in the dermis after a short application to the skin and release antigen over 1–2 weeks, mimicking the time course of a natural influenza infection. In a preclinical murine model, a single influenza vaccine administration via MIMIX led to faster seroconversion, response-equivalence to prime-boost bolus immunization, higher HAI titers against drifted influenza strains, and improved protective efficacy upon lethal influenza challenge when compared with intramuscular injection. These results highlight infection mimicry, achieved through sustained release silk microneedles, as a powerful approach to improve existing seasonal influenza vaccines, while also suggesting the broader potential of this platform technology to enable more efficacious next-generation vaccines and vaccine combinations.