Extended delivery of vaccines to the skin improves immune responses

Abstract

Vaccines prevent 2-3 million childhood deaths annually; however, low vaccine efficacy and the resulting need for booster doses create gaps in immunization coverage. In this translational study, we explore the benefits of extended release of licensed vaccine antigens into skin to increase immune responses after a single dose in order to design improved vaccine delivery systems. By administering daily intradermal injections of inactivated polio vaccine according to six different delivery profiles, zeroth-order release over 28 days resulted in neutralizing antibody titers equivalent to two bolus vaccinations administered one month apart. Vaccinations following this profile also improved immune responses to tetanus toxoid and subunit influenza vaccine but not, a live-attenuated viral vaccine, measles vaccine. Finally, using subunit influenza vaccine, we demonstrated that daily vaccination by microneedle patch induced a potent, balanced humoral immunity with an increased memory response compared to bolus vaccination. We conclude that extended presentation of antigen in skin via intradermal injection or microneedle patch can enhance immune responses and reduce the number of vaccine doses, thereby enabling increased vaccination efficacy.

Microarray patches enable the development of skin-targeted vaccines against COVID-19

“…Hybrid MAPs have been used to implant biodegradable polymer (e.g., chitosan) microarray tips into animal skin through their rapid separation from the stems to achieve controlled release of vaccine components in the cutaneous microenvironment [ 250 , 338 ]. Consistent with studies demonstrating improved immunogenicity of antigens delivered in a sustained manner by daily or repeated injections, extended release of vaccine components from hybrid or other MAP types resulted in improved adaptive immune responses [ 250 , [339] , [340] , [341] , [342] , [343] , [344] ]. Ultimately, hydrogel-forming, porous, and hybrid MAPs represent alternatives for skin-targeted immunization against emerging infectious diseases.…”

cGAMP/Saponin Adjuvant Combination Improves Protective Response to Influenza Vaccination by Microneedle Patch in an Aged Mouse Model

“…Physical adjuvantation may also come from formulation of the MNPs using a water-soluble polymer that forms a gel upon contact with interstitial fluid in the skin. As the gel dissolves and the antigen and adjuvant(s) slowly diffuse away from the site of MNP application, the antigen and adjuvant(s) have a more extended presentation to the immune system, which can lead to improved immune responses ( 36 ). Other factors, such as the presence of skin-resident antigen-presenting cells, for example Langerhans cells and dermal dendritic cells, as well as lymphatics draining from the skin may also contribute to the efficacy of skin vaccination by MNPs ( 37 , 38 ).…”

Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid

“…One promising approach for ISF extraction is the use of microneedle (MN) array patches 13–15. Historically, MNs were developed for the delivery of drugs,16–18 vaccines,19,20 biomolecules,21,22 or stem cells 23. The extensive focus on developing MN‐based delivery approaches rather than extraction methods may be the result of the lack of excellent ISF‐absorbing materials.…”