Site-Specific Antimicrobial Activity of a Dual-Responsive Ciprofloxacin Prodrug.

Bacterial infections create distinctive microenvironments with a unique mix of metabolites and enzymes compared with healthy tissues that can be used to trigger the activation of antibiotic prodrugs. Here, a single and dual prodrug masking the C3 carboxylate and C7 piperazine of the fluoroquinolone, ciprofloxacin, responsive to nitroreductase (NTR) and/or hydrogen sulfide (H2S), was developed. Masking both functional groups reduced the activity of the prodrug against Staphylococcus aureus and Escherichia coli, increasing its minimum inhibitory concentration (MIC) by ∼512-fold (S. aureus) and ∼8000-fold (E. coli strains), while masking a single group only increased the MIC by ∼128-fold. Bacteria subjected to prolonged prodrug exposure did not show any increase in resistance. Triggering assays demonstrated the conversion of prodrugs to ciprofloxacin, and in a murine infection model, responsive prodrugs showed antibacterial activity comparable to that of ciprofloxacin, suggesting in vivo activation of prodrugs. Thus, the potential for site-specific antibiotic treatment with reduced threat of resistance is demonstrated.

Lyme disease vaccine attitudes and intentions among parents of children aged 5-18 years in the United States.

BACKGROUND: Lyme disease (LD) is the most common vector-borne disease in the United States, with increasing incidence and geographic range. Case incidence peaks among school-aged children. New LD preventives are in clinical trials. METHODS: We conducted an online survey of parents of children aged 5-18 years in states with high or emerging incidence of LD. Our primary outcome was willingness ("definitely" or "probably") for their child to receive an LD vaccine. Our secondary outcome was preference for annual monoclonal antibody injections compared to a 3-dose vaccine series with boosters. Analyses were weighted to reflect parent gender, parent race/ethnicity, and child age by state. RESULTS: Among 1,351 parent respondents, most (68.0 %) would have their child vaccinated against LD, with significantly more being willing in high compared to emerging incidence states (70.4 % versus 63.6 %, p = 0.027). Of parents who were unsure or unwilling, 33.5 % and 16.5 %, respectively, would do so with a provider recommendation. Vaccine safety concerns were among the top reasons for LD vaccine hesitancy. More parents preferred a pre-formed antibody (42.3 %) compared to a 3-dose vaccine series (34.7 %). Significant predictors of willingness to have one's child vaccinated were higher parental education; higher perceived risk of child getting LD; child spending time outdoors daily or weekly; following a regular vaccine schedule; and positive attitude towards vaccines. Significant predictors of preference for monoclonal antibody over a 3-dose vaccine series included prior awareness of LD, living in a rural area, and less positive attitudes towards vaccines. CONCLUSIONS: Two-thirds of parents in high and emerging incidence states would vaccinate their children against Lyme disease. Addressing safety concerns will be important, and a health care provider recommendation could also encourage those who are unsure or unwilling. Given the slight preference for monoclonal antibody over vaccine, particularly in rural areas, access to both may increase LD prevention.

Acceptability of 4-poster deer treatment devices for community-wide tick control among residents of high Lyme disease incidence counties in Connecticut and New York, USA.

The 4-Poster Tick Control Deer Feeder (4-poster) device applies acaricide to white-tailed deer (Odocoileus virginianus) and can reduce populations of the blacklegged tick (Ixodes scapularis), which transmits the agents of Lyme disease, anaplasmosis, babesiosis, and Powassan virus disease in the Northeastern United States. While 4-poster devices have the potential to provide community-wide management of blacklegged ticks in Lyme disease endemic areas, no recent study has assessed their acceptability among residents. We conducted a survey of residents from 16 counties with high annual average Lyme disease incidence (≥ 10 cases per 100,000 persons between 2013 and 2017) in Connecticut and New York to understand perceptions and experiences related to tickborne diseases, support or concerns for placement of 4-poster devices in their community, and opinions on which entities should be responsible for tick control on private properties. Overall, 37% of 1652 respondents (5.5% response rate) would support placement of a 4-poster device on their own property, 71% would support placement on other private land in their community, and 90% would support placement on public land. Respondents who were male, rented their property, resided on larger properties, or were very or extremely concerned about encountering ticks on their property were each more likely to support placement of 4-poster devices on their own property. The primary reason for not supporting placement of a 4-poster device on one's own property was the need for weekly service visits from pest control professionals, whereas the top reason for not supporting placement on other land (private or public) was safety concerns. Most respondents (61%) felt property owners should be responsible for tick control on private properties. Communities considering 4-poster devices as part of a tick management strategy should consider targeting owners of larger properties and placing devices on public lands.

Impacts Over Time of Neighborhood-Scale Interventions to Control Ticks and Tick-Borne Disease Incidence.

Background: Controlling populations of ticks with biological or chemical acaricides is often advocated as a means of reducing human exposure to tick-borne diseases. Reducing tick abundance is expected to decrease immediate risk of tick encounters and disrupt pathogen transmission cycles, potentially reducing future exposure risk. Materials and Methods: We designed a placebo-controlled, randomized multiyear study to assess whether two methods of controlling ticks-tick control system (TCS) bait boxes and Met52 spray-reduced tick abundance, tick encounters with people and outdoor pets, and reported cases of tick-borne diseases. The study was conducted in 24 residential neighborhoods in a Lyme disease endemic zone in New York State. We tested the hypotheses that TCS bait boxes and Met52, alone or together, would be associated with increasing reductions in tick abundance, tick encounters, and cases of tick-borne disease over the 4-5 years of the study. Results: In neighborhoods with active TCS bait boxes, populations of blacklegged ticks (Ixodes scapularis) were not reduced over time in any of the three habitat types tested (forest, lawn, shrub/garden). There was no significant effect of Met52 on tick abundance overall, and there was no evidence for a compounding effect over time. Similarly, we observed no significant effect of either of the two tick control methods, used singly or together, on tick encounters or on reported cases of tick-borne diseases in humans overall, and there was no compounding effect over time. Thus, our hypothesis that effects of interventions would accumulate through time was not supported. Conclusions: The apparent inability of the selected tick control methods to reduce risk and incidence of tick-borne diseases after years of use requires further consideration.

Association Between Prolonged Shedding of Zika Virus in Human Semen and Male Reproductive Tract Inflammation.

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes congenital defects. Sexual transmission of ZIKV was confirmed in a recent epidemic; however, mechanisms behind ZIKV infection and persistence in the male reproductive tract (MRT) are unknown. Previously, we found that approximately 33% of men with symptomatic ZIKV infections shed ZIKV RNA in semen, and some men shed ZIKV RNA for >3 months. Here, we evaluated the semen of 49 ZIKV-infected men to identify immune factors correlating with long-term ZIKV shedding in semen and ZIKV-infected cell types in semen. We found that prolonged ZIKV RNA shedding in semen was associated with MRT inflammation, indicated by higher leukocyte counts and inflammatory cytokine concentrations in semen of long-term versus short-term shedders. In addition, we found ZIKV RNA in seminal leukocytes and epithelial cells. This study of human semen from ZIKV-infected men provides critical insights into the effects of ZIKV on MRT health.

Development of a bioorthogonal fluorescence-based assay for assessing drug uptake and delivery in bacteria.

Bioorthogonal chemistry can facilitate the development of fluorescent probes that can be used to sensitively and specifically detect the presence of biological targets. In this study, such an assay was developed to evaluate the uptake and delivery of antimicrobials into Escherichia coli, building on and extending previous work which utilised more resource intensive LCMS detection. The bacteria were genetically engineered to express streptavidin in the periplasmic or cytoplasmic compartments, which was used to localise a bioorthogonal probe (BCN-biotin). Azido-compounds which are delivered to these compartments react with the localised BCN-biotin-streptavidin in a concentration-dependent manner via a strain-promoted alkyne-azide cycloaddition. The amount of azido-compound taken up by bacteria was determined by quantifying unreacted BCN-biotin-streptavidin via an inverse electron demand Diels-Alder reaction between remaining BCN-biotin and a tetrazine-containing fluorescent dye. Following optimisation and validation, the assay was used to assess uptake of liposome-formulated azide-functionalised luciferin and cefoxitin. The results demonstrated that formulation into cationic liposomes improved the uptake of azide-functionalised compounds into the periplasm of E. coli, providing insight on the uptake mechanism of liposomes in the bacteria. This newly developed bioorthogonal fluorescence plate-reader based assay provides a bioactivity-independent, medium-to-high throughput tool for screening compound uptake/delivery.

Economic Burden of Reported Lyme Disease in High-Incidence Areas, United States, 2014-2016.

Approximately 476,000 cases of Lyme disease are diagnosed in the United States annually, yet comprehensive economic evaluations are lacking. In a prospective study among reported cases in Lyme disease-endemic states, we estimated the total patient cost and total societal cost of the disease. In addition, we evaluated disease and demographic factors associated with total societal cost. Participants had a mean patient cost of ≈$1,200 (median $240) and a mean societal cost of ≈$2,000 (median $700). Patients with confirmed disseminated disease or probable disease had approximately double the societal cost of those with confirmed localized disease. The annual, aggregate cost of diagnosed Lyme disease could be $345-968 million (2016 US dollars) to US society. Our findings emphasize the importance of effective prevention and early diagnosis to reduce illness and associated costs. These results can be used in cost-effectiveness analyses of current and future prevention methods, such as a vaccine.

Effects of Tick-Control Interventions on Tick Abundance, Human Encounters with Ticks, and Incidence of Tickborne Diseases in Residential Neighborhoods, New York, USA.

Tickborne diseases (TBDs) such as Lyme disease result in ≈500,000 diagnoses annually in the United States. Various methods can reduce the abundance of ticks at small spatial scales, but whether these methods lower incidence of TBDs is poorly understood. We conducted a randomized, replicated, fully crossed, placebo-controlled, masked experiment to test whether 2 environmentally safe interventions, the Tick Control System (TCS) and Met52 fungal spray, used separately or together, affected risk for and incidence of TBDs in humans and pets in 24 residential neighborhoods. All participating properties in a neighborhood received the same treatment. TCS was associated with fewer questing ticks and fewer ticks feeding on rodents. The interventions did not result in a significant difference in incidence of human TBDs but did significantly reduce incidence in pets. Our study is consistent with previous evidence suggesting that reducing tick abundance in residential areas might not reduce incidence of TBDs in humans.

Liposomes with cyclodextrin channels and polyethyleneimine (PEI) improves cytoplasmic vaccine delivery and induces anti-cancer immune activity in mice.

Cancer vaccines have been developed as an additional method of treatment in the fight against cancer. However, an important barrier to an effective vaccine is the inefficient presentation of exogenous antigen by dendritic cells to cytotoxic CD8 T cells. In this study, DPPC liposomes were modified with channels and loaded with polyethyleneimine (PEI) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) to produce a vaccine carrier. The liposomes were designed to be pH responsive to facilitate delivery of antigens directly to the cytoplasm of antigen presenting cells, bypassing the cross-presentation pathway and improving cellular immune responses. The lysis of liposomes in acidic cell-free conditions was measured using a validated dynamic light scattering assay in order to gain an insight into the mechanism of PEI-mediated lysis. Dendritic cell stimulation and T cell proliferation was investigated in vitro and the potential of this formulation to stimulate a therapeutic anti-cancer immune response was examined in a murine melanoma model. The modified formulation stimulated T cell activation in vitro and induced a small but significant increase in survival in immunized mice. Overall, liposomes modified with PEI and channels successfully delivered antigen to the cytoplasm of dendritic cells, which subsequently led to the development of an appropriate immune response.

Understanding consumer and clinician perceptions of a potential Lyme disease vaccine.

Each year, over 450 000 Lyme disease diagnoses are estimated to occur in the United States, and current preventive measures have been insufficient to stem the rising incidence. An effective human Lyme disease vaccine could be a powerful intervention for population-level impact. In advance of new Lyme disease vaccines coming to market, this study explored barriers to acceptability and motivations for the uptake of a new Lyme disease vaccine. Researchers conducted 9 online focus groups among consumers who may potentially benefit from the vaccine and 30 in-depth interviews among clinician groups who may provide the vaccine. All participants were recruited from three US regions of high Lyme disease incidence. Researchers found that participants shared common motivators to either recommend (clinicians) or accept (consumers) a Lyme disease vaccine, largely driven by perceived benefits of the vaccine, the lack of current effective preventive measures and a greater peace of mind. The concern about the challenges associated with diagnosing and treating Lyme disease is a primary motivator for clinicians to recommend the vaccine, while the concern about getting Lyme disease is a primary motivator for consumers to desire the vaccine.

Willingness to Pay for Select Tick-Borne Disease Prevention Measures in Endemic Areas.

Tick-borne diseases (TBDs) are increasing despite prevention recommendations. We explored whether cost is a barrier to prevention use in Connecticut and Maryland, using a cross-sectional survey. Respondents were queried regarding their willingness to pay for chemical, natural, and rodent-targeted yard pesticide treatments and permethrin-treated clothing. We evaluated associations between demographics, TBD knowledge and attitudes, and willingness to pay for prevention methods. Most respondents would pay for yard treatments (85%); 95% preferring natural pesticide, and 82% would pay for permethrin-treated clothing. Most did not want to pay more than $99 for any of the yard treatments. Having a household income of $100 000 was associated with willingness to pay $100 or more for chemical, natural, or rodent-targeted treatments and $25 or more for permethrin self-treated and pretreated clothing. Yard treatments, especially natural pesticides, were acceptable for TBD prevention; however, current pricing may be cost-prohibitive. Permethrin-treated clothing may be an affordable and acceptable prevention method.

Evaluating public acceptability of a potential Lyme disease vaccine using a population-based, cross-sectional survey in high incidence areas of the United States.

BACKGROUND: Lyme disease incidence is increasing, despite current prevention options. New Lyme disease vaccine candidates are in development, however, investigation of the acceptability of a Lyme disease vaccine among potential consumers is needed prior to any vaccine coming to market. We conducted a population-based, cross-sectional study to estimate willingness to receive a potential Lyme disease vaccine and factors associated with willingness. METHODS: The web-based survey was administered to a random sample of Connecticut, Maryland, Minnesota, and New York residents June-July 2018. Survey-weighted descriptive statistics were conducted to estimate the proportion willing to receive a potential Lyme disease vaccine. Multivariable multinomial logistic regression models were used to quantify the association of sociodemographic characteristics and Lyme disease vaccine attitudes with willingness to be vaccinated. RESULTS: Surveys were completed by 3313 respondents (6% response rate). We estimated that 64% of residents were willing to receive a Lyme disease vaccine, while 30% were uncertain and 7% were unwilling. Compared to those who were willing, those who were uncertain were more likely to be parents, adults 45-65 years old, non-White, have less than a bachelor's degree, or have safety concerns about a potential Lyme disease vaccine. Those who were unwilling were also more likely to be non-White, have less than a bachelor's degree, or have safety concerns about a potential Lyme disease vaccine. In addition, the unwilling had low confidence in vaccines in general, had low perceived risk of contracting Lyme disease, and said they would not be influenced by a positive recommendation from a healthcare provider. DISCUSSION: Overall, willingness to receive a Lyme disease vaccine was high. Effective communication by clinicians regarding safety and other vaccine parameters to those groups who are uncertain will be critical for increasing vaccine uptake and reducing Lyme disease incidence.

Covid-19 Rates by Time since Vaccination during Delta Variant Predominance.

BACKGROUND: With the emergence of the delta variant, the United States experienced a rapid increase in Covid-19 cases in 2021. We estimated the risk of breakthrough infection and death by month of vaccination as a proxy for waning immunity during a period of delta variant predominance. METHODS: Covid-19 case and death data from 15 U.S. jurisdictions during January 3 to September 4, 2021 were used to estimate weekly hazard rates among fully vaccinated persons, stratified by age group and vaccine product. Case and death rates during August 1 to September 4, 2021 were presented across four cohorts defined by month of vaccination. Poisson models were used to estimate adjusted rate ratios comparing the earlier cohorts to July rates. RESULTS: During August 1 to September 4, 2021, case rates per 100,000 person-weeks among all vaccine recipients for the January to February, March to April, May to June, and July cohorts were 168.8 (95% confidence interval [CI], 167.5 to 170.1), 123.5 (95% CI, 122.8 to 124.1), 83.6 (95% CI, 82.9 to 84.3), and 63.1 (95% CI, 61.6 to 64.6), respectively. Similar trends were observed by age group for BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccine recipients. Rates for the Ad26.COV2.S (Janssen-Johnson & Johnson) vaccine were higher; however, trends were inconsistent. BNT162b2 vaccine recipients 65 years of age or older had higher death rates among those vaccinated earlier in the year. Protection against death was sustained for the mRNA-1273 vaccine recipients. Across age groups and vaccine types, people who were vaccinated 6 months ago or longer (January-February) were 3.44 (3.36 to 3.53) times more likely to be infected and 1.70 (1.29 to 2.23) times more likely to die from COVID-19 than people vaccinated recently in July 2021. CONCLUSIONS: Our study suggests that protection from SARS-CoV-2 infection among all ages or death among older adults waned with increasing time since vaccination during a period of delta predominance. These results add to the evidence base that supports U.S. booster recommendations, especially for older adults vaccinated with BNT162b2 and recipients of the Ad26.COV2.S vaccine. (Funded by the Centers for Disease Control and Prevention.).

Hydrogen Sulfide-Responsive Bicontinuous Nanospheres.

Block copolymers (BCPs) that can self-assemble into particles and be triggered by disease-specific molecules such as hydrogen sulfide (H2S) have the potential to impact on drug delivery, decreasing off-target toxicities while increasing drug efficacy. However, the incorporation of H2S-responsive aryl azides into BCPs for self-assembly has been limited by heat, light, and radical sensitivities. In this study, a robust activator regenerated by the electron-transfer atom-transfer radical polymerization reaction was used to synthesize aryl-azide-containing BCPs under ambient conditions. Conditions controlling self-assembly of the BCPs into 150-200 nm particles and the physicochemical properties of the particles were investigated. The use of nanoprecipitation with tetrahydrofuran to promote self-assembly of the BCPs resulted in vesicle structures, while dimethylformamide or dimethylsulfoxide resulted in polymeric bicontinuous nanospheres (BCNs). Triggering of the BCPs and particles (vesicles or BCNs) via exposure to H2S revealed that unsubstituted aryl azides were readily reduced (by HS-), resulting in particle disruption or cross-linking. The relative polar nature of the particle bilayers containing unsubstituted aryl azides and the open structure of the BCNs did however limit encapsulation of small hydrophilic and hydrophobic payloads. Incorporation of a benzylamide substituent onto the aryl azide group increased the hydrophobicity of the particles and encapsulation of hydrophilic cargo but reduced sensitivity to H2S, likely due to the reduced penetration of HS- into the bilayer.

Bacteria biohybrid oral vaccines for colorectal cancer treatment reduce tumor growth and increase immune infiltration.

Bacteria biohybrid-based vaccine delivery systems, which integrate a vaccine carrier with live non-pathogenic bacteria, are hypothesized to have improved immunostimulating potential. The aim of this study was to develop oral bacteria biohybrid-based vaccines to treat a mouse model of colorectal cancer. E. coli were combined with tumor antigen- and adjuvant-containing emulsions or liposomes. Emulsion and liposome biohybrid vaccines demonstrated in vitro and in vivo therapeutic potential. Bacteria biohybrid vaccines significantly increased the expression of CD40+, CD80+ and CD86+ on murine bone marrow-derived dendritic cells. Mice vaccinated with emulsion biohybrid vaccines had an increased CD8+ T cell infiltration into tumors and developed three-fold smaller tumors compared to the mice that received emulsion vaccine without E. coli.

EGFR-targeted prodrug activation using bioorthogonal alkene-azide click-and-release chemistry.

Epidermal growth factor receptor (EGFR) is overexpressed in many cancers and therefore serves as an excellent target for prodrug activation. Functionalised trans-cyclooctenes (TCO) were conjugated to an EGFR antibody (cetuximab), providing a reagent for pre-targeting and localisation of the bioorthogonal reagent. The TCOs react with a 4-azidobenzyl carbamate doxorubicin prodrug via a [3 + 2]-cycloaddition and subsequent self-immolation leads to release of doxorubicin (click-and-release). In vitro cell-based assays demonstrated proof-of-concept, that cetuximab conjugated to highly strained TCO (AB-d-TCO) could bind to the EGFR in a melanoma cell line, and selectively activate the doxorubicin prodrug. In a non-EGFR expressing melanoma cell line, no significant prodrug activation was observed. In vivo experiments using this combination of AB-d-TCO and the azido-doxorubicin prodrug in a murine melanoma model revealed no significant anti-tumour activity or increased survival, suggesting there was insufficient prodrug activation and drug release at the tumour site.

Prevention of Lyme and other tickborne diseases using a rodent-targeted approach: A randomized controlled trial in Connecticut.

Tickborne diseases are an increasing public health problem in the northeastern USA. Bait boxes that apply acaricide to rodents have been shown in small field studies to significantly reduce abundance of Ixodes scapularis ticks as well as their pathogen infection rates in treated areas. The effectiveness of this intervention for preventing human tickborne diseases (TBDs) has not been demonstrated. During 2012-2016, TickNET collaborators conducted a randomized, blinded, placebo-controlled trial among 622 Connecticut households. Each household received active (containing fipronil wick) or placebo (empty) bait boxes in their yards over two consecutive years. Information on tick encounters and TBDs among household members was collected through biannual surveys. Nymphal ticks were collected from a subset of 100 properties during spring at baseline, during treatment, and in the year post-intervention. Demographic and property characteristics did not differ between treatment groups. There were no significant differences post-intervention between treatment groups with respect to tick density or pathogen infection rates, nor for tick encounters or TBDs among household members. We found no evidence that rodent-targeted bait boxes disrupt pathogen transmission cycles or significantly reduce household risk of tick exposure or TBDs. The effectiveness of this intervention may depend on scale of use or local enzootic cycles.

Cubosomes enhance drug permeability across the blood-brain barrier in zebrafish.

The potential of cubosomes to improve delivery of incorporated cargo to the brain was explored in zebrafish. Cubosomes were formulated with one of three stabilisers, Pluronic F68, Pluronic F127 or Tween 80, with the hypothesis that coating with Tween 80 will enable brain targeting of cubosomes as has been previously shown for polymeric nanoparticles. The physiochemical properties and the ability of the cubosomes to facilitate delivery of the model drug lissamine rhodamine (RhoB) into the brain was investigated. Distribution of cubosomes in the midbrain was also investigated by ultrastructural analysis via incorporation of octanethiol-functionalized gold nanoparticles. Cubosomes were typically 165-195 nm in size with a Pn3m (Pluronics) or Im3m (Tween 80) cubic phase internal structure. Cubosomes were injected intravenously into zebrafish larvae (12-14 days post fertilization) and the concentration of RhoB in the midbrain was determined by quantifying its fluorescence intensity. Uptake of RhoB was significantly greater in larvae injected with Tween 80 stabilized cubosomes as compared to a control suspension of RhoB or cubosomes stabilized with Pluronics. Collectively, we show for the first time that cubosomes can be functionalized to deliver drug across the BBB, offering new opportunities to overcome drug delivery issues across this formidable biological barrier.

Human-tick encounters as a measure of tickborne disease risk in lyme disease endemic areas.

Entomological measures have long served as proxies for human risk of Lyme disease (LD) and other tickborne diseases (TBDs) in endemic areas of the United States, despite conflicting results regarding the correlation between these measures and human disease outcomes. Using data from a previous TBD intervention study in Connecticut, Maryland and New York, we evaluated whether human-tick encounters can serve as an accurate proxy for risk of TBDs in areas where LD and other Ixodes scapularis-transmitted infections are common. Among 2,590 households consisting of 4,210 individuals, experiencing a tick encounter was associated with an increased risk of both self-reported (RR = 3.17, 95% CI: 2.05, 4.91) and verified TBD (RR = 2.60, 95% CI: 1.39, 4.84) at the household level. Household characteristics associated with experiencing any tick encounter were residence in Connecticut (aOR = 1.86, 95% CI: 1.38, 2.51) or New York (aOR = 1.66, 95% CI: 1.25, 2.22), head of household having a graduate level education (aOR = 1.46, 95% CI: 1.04, 2.08), owning a pet (aOR = 1.80, 95% CI: 1.46, 2.23) and a property size of 2 acres or larger (aOR = 2.30, 95% CI: 1.42, 3.70). Results for individual characteristics were similar to those for households. Future prevention studies in LD endemic areas should consider using human-tick encounters as a robust proxy for TBD risk.

Vaccine implants: current status and recent advancements.

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.