Vaccine implants: current status and recent advancements

Abstract

Implants have long been used in the field of drug delivery as controlled release vehicles and are now being investigated as single-shot vaccine technologies. Implants have shown great promise, minimizing the need for multiple immunizations while stimulating potent immune responses with reduced doses of vaccine. Synchronous release of vaccine components from implants over an appropriate period of time is important in order to avoid issues including immune tolerance, sequestration or deletion. Traditionally, implants require surgical implantation and removal, which can be a barrier to their widespread use. Degradable and in situ implants are now being developed that can be administered using minimally invasive subcutaneous or intramuscular injection techniques. Injectable hydrogels remain the most commonly studied approach for sustained vaccine delivery due to their ease of administration and tunable degradation properties. Despite exciting advancements in the field of vaccine implants, few technologies have progressed to clinical trials. To increase the likelihood of clinical translation of vaccine implants, strategic testing of disease-relevant antigens in appropriate species is essential. In this review, the significance of vaccine implants and the different types of implants being developed to deliver vaccines are discussed.

Practical Considerations for Next-Generation Adjuvant Development and Translation

“…Controlled-release systems are generally designed for use with protein subunit antigens, and many have incorporated adjuvants to enhance the immunogenicity of these vaccines. To this end, many adjuvants have been included in a number of controlled-release vaccine systems, but most are off-the-shelf materials as opposed to fit-for-purpose compositions, including MPL, Alum, and CpG (among others) [ 75 ]. These adjuvants, while effective, are unlikely to be optimal in the unique kinetics of a controlled-release system without additional modification.…”

“…From a design perspective, implantable vaccines that have an active lifespan of weeks to months would be best served by a biodegradable material; otherwise, the requirement for removal of the device defeats many potential patient benefits. To this end, many biodegradable materials have been explored, including poly(D,L-lactic acid-co-glycolic acid) and polyanhydride as implants and various materials in gels, such as a variety of polyester and polyethylene block-copolymers, polysaccharide polymers like alginate or chitosan, synthetic peptide scaffolds, and cellulose derivatives (among others) [ 75 ]. From a use standpoint, vaccine products, in general, are dependent on high uptake in relevant populations, meaning that dosing procedures that are more complex than a standard percutaneous injection will be more challenging to market [ 76 , 77 ].…”

“…From a use standpoint, vaccine products, in general, are dependent on high uptake in relevant populations, meaning that dosing procedures that are more complex than a standard percutaneous injection will be more challenging to market [ 76 , 77 ]. For this reason, shear-thinning or in situ crosslinking materials are likely to have a market advantage over solid form factors that will require more complex outpatient procedures to place correctly [ 75 ]. A potential advantage of these novel polymer-gel systems is that adjuvants can interact directly with the chemistry of the material to better synchronize release with a protein antigen [ 78 , 79 ].…”

A Single‐Administration Microneedle Skin Patch for Multi‐Burst Release of Vaccine against SARS‐CoV‐2

“…Some researchers have developed MNs for the sustained delivery of small‐molecule drugs or vaccines; [ 17 , 18 ] however, there is a requirement for appropriately controlled release time in order to avoid the risk that the sustained release of vaccines could elicit immune tolerance responses. [ 19 , 20 ] These shortcomings of current MN patches together make them suboptimal for use in global vaccination efforts. In this context, we have recently reported the use of single‐administration multi‐burst release core–shell MNs for the delivery of a clinically relevant vaccine against Streptococcus pneumoniae , Prevnar‐13.…”