Delivery of subunit influenza vaccine to skin with microneedles improves immunogenicity and long-lived protection

Abstract

Influenza infection represents a major socio-economic burden worldwide. Novel delivery methods can render influenza vaccination easier and more acceptable by the public, and importantly confer protection equal or superior to that induced by conventional systemic administration. An attractive target for vaccine delivery is the skin. Recent studies have demonstrated improved immune responses after transdermal delivery of inactivated influenza virus with microneedle patches. Here we show that immunization with a licensed influenza subunit vaccine coated on metal microneedles can activate both humoral and cellular arms of the immune response and confer improved long-term protection in the mouse model when compared to the conventional systemic route of delivery. These results demonstrate the promising potential of microneedle delivery of licensed influenza subunit vaccines, that could be beneficial in increasing vaccine coverage and protection and reducing influenza-related mortality worldwide.

Enhanced Immunogenicity of an HIV-1 DNA Vaccine Delivered with Electroporation via Combined Intramuscular and Intradermal Routes

“…i.m. vaccination has been described to result in poor antigen-dependent T cell activation owing to the lack of APCs in muscle tissue (14). Certainly, previous studies have shown that i.d.…”

“…For instance, while most vaccinations, including DNA, are delivered via the i.m. route (13), the lower number of antigen-presenting cells (APCs) within muscle tissues has been suggested to be a factor contributing to reduced efficacy (2,5,14). i.m.…”

Nano- and micro-based systems for immunotolerance induction in multiple sclerosis

“…It was demonstrated that vaccination using microneedles triggers stronger immune responses comparing to conventional injection procedures, allowing sparing of antigens. 38 Indeed, the use of microneedle-based devices for influenza vaccination is currently under clinical trials.…”

A Viable Recombinant Rhabdovirus Lacking Its Glycoprotein Gene and Expressing Influenza Virus Hemagglutinin and Neuraminidase Is a Potent Influenza Vaccine

“…Cells were washed with phosphate-buffered saline (PBS) and lysed with detergent lysis buffer (1% Nonidet P-40, 0.4% deoxycholate, 50 mM Tris-HCl [pH 8.0], 62.5 mM EDTA) on ice for 5 min. Lysates were subjected to SDS-PAGE on a 4 to 12% Bis-Tris NuPAGE gel (Invitrogen, CA).…”

“…The influenza virus surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are key mediators of the viral infectious cycle and obvious proteins of interest for novel vaccines. The majority of recent vaccine candidates focus predominantly on the immunogenic properties of the influenza virus HA, and sometimes NA, glycoprotein, seeking to utilize vector systems (1)(2)(3), adjuvants (4)(5)(6), alternative routes of immunization (7,8), and novel antigen presentation and delivery systems (9)(10)(11)(12) to increase humoral and/or cell-mediated immunity against these and other influenza virus antigens. Creating vaccines that also exploit the functional properties of the influenza virus glycoproteins represents a unique approach.…”