Targeted Vaccine Delivery Research Articles

Vaccine enhancement and improved immunogenicity using erythrocytes as carriers

Achieving optimal immunogenicity and efficacy in vaccination presents significant challenges, including the need for multiple doses and the limited immunogenicity observed with certain vaccine formulations. To overcome these obstacles, researchers are exploring supplementary components and innovative delivery strategies. The development of an effective vaccine delivery technology is crucial for achieving sufficient protective immunity and disease prevention. This article focuses on the potential of erythrocytes as vaccine carriers to enhance vaccine effectiveness, particularly in the context of whole particle vaccines. The extended lifespan of erythrocytes enables sustained antigen exposure, resulting in continuous antigen presentation to immune cells. Moreover, erythrocytes exhibit biocompatibility, a well-established safety profile, and the capacity to modulate immune responses through interactions with complement receptors. These characteristics position erythrocytes as an appealing platform for targeted vaccine delivery. The hypothesis suggests utilizing bispecific monoclonal antibodies to complement receptor 1 and specific pathogen proteins to hitchhike inactivated pathogens onto erythrocytes. These modified erythrocytes can then serve as carriers to deliver the whole particle vaccine to antigen-presenting cells (APCs) or function as APCs themselves in the spleen. This article puts forward treatment protocols aimed at improving accessibility of vaccinations at the appropriate location, reducing the frequency of vaccine doses, and stimulating sufficient protective immunity.

Lipid-based colloidal nanoparticles for applications in targeted vaccine delivery.

Bioactive molecules and their effects have been influenced by their solubility and administration route. In many therapeutic reagents, the performance of therapeutics is dependent on physiological barriers in the human body and delivery efficacy. Therefore, an effective and stable therapeutic delivery promotes pharmaceutical advancement and suitable biological usage of drugs. In the biological and pharmacological industries, lipid nanoparticles (LNPs) have emerged as a potential carrier to deliver therapeutics. Since studies reported doxorubicin-loaded liposomes (Doxil®), LNPs have been applied to numerous clinical trials. Lipid-based nanoparticles, including liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid nanoparticles, have also been developed to deliver active ingredients in vaccines. In this review, we present the type of LNPs used to develop vaccines with attractive advantages. We then discuss messenger RNA (mRNA) delivery for the clinical application of mRNA therapeutic-loaded LNPs and recent research trend of LNP-based vaccine development.

Lipid Nanobiotechnology: An Alternative Strategy to Targeted Drug and Vaccine Delivery System and Its Biomedical Applications as Nanomedicine

Nanobiotechnology has very compelling role in vaccine development. Delivery system orientates toward less immunogenic minimal compositions and formulations that boost antigen effectiveness. Latest advancements in LNPs formulations as targeted vaccine delivery systems, like anticancer and nucleic acid therapeutics. Nanomedicine expel challenges and promote growth opportunities inareas, like biomedical imaging, nutraceuticals, biomedicine, gene technology, and basic sciences. The fundamental understanding regarding the in-vivo behavior of nanoparticles explored, which can perform as either a delivery system to enhance antigen processing and/or as an immunostimulant adjuvant to activate or enhance immunity. The utilization of nanoparticles in vaccine development allows targeted delivery, improved antigen stability and immunogenicity.

COVID-19 vaccine coverage and factors associated with vaccine uptake among individuals with a recent experience of homelessness: a population-based analysis from Ontario, Canada.

ObjectivesTo describe COVID-19 vaccine coverage (i.e., the estimated percentage of people who have received a vaccine) and determinants of vaccine receipt among individuals with a recent experience of homelessness in Ontario, Canada. ApproachWe conducted a retrospective, population-based cohort study of 23,247 individuals (≥18 years) with a recent experience of homelessness as recorded in routinely collected healthcare databases. Participants were followed from December 14, 2020 to September 30, 2021 for the receipt of a COVID-19 vaccine. Using modified Poisson regression, we identified sociodemographic, healthcare usage, and clinical factors associated with the receipt of one or more doses of a COVID-19 vaccine. ResultsBy September 30, 14,271 (61.4%) of participants with a recent experience of homelessness had received a first dose of a COVID-19 vaccine and 11,082 (47.7%) had received two doses. Over the same period, 86.6% and 81.6% of the total adult population of Ontario had received a first dose and second dose, respectively. In multivariable analysis, factors associated with increased COVID-19 uptake included ≥1 visit to a general practitioner (adjusted Risk Ratio [aRR]:1.37[95% CI 1.31-1.42]), older age (vs. 18-29 years: 50-59 years, aRR:1.18[1.14-1.22]; 60+ years, aRR:1.27[1.22-1.31]), receipt of an influenza vaccine (aRR:1.25[1.23-1.28]), receipt of ≥1 SARS-CoV-2 test (aRR:1.23[1.20-1.26]) and the presence of chronic health conditions (vs. 0 conditions: 1 condition, aRR:1.05[1.03, 1.08]; 2+ conditions, aRR:1.11[1.08-1.14]). In contrast, living in a smaller metropolitan region (aRR:0.92[0.90-0.94]) or rural location (aRR:0.93[0.90-0.97]) compared to a large metropolitan region was associated with lower uptake. ConclusionsAs of September 30, 2021, COVID-19 vaccine coverage among individuals with a recent experience of homelessness in Ontario was substantially lower than the general adult population of Ontario for a first and second dose. Findings underscore the importance of leveraging organizations that are accessed and trusted by people who experience homelessness for targeted vaccine delivery.

Variation in the COVID-19 infection–fatality ratio by age, time, and geography during the pre-vaccine era: a systematic analysis

SummaryBackgroundThe infection–fatality ratio (IFR) is a metric that quantifies the likelihood of an individual dying once infected with a pathogen. Understanding the determinants of IFR variation for COVID-19, the disease caused by the SARS-CoV-2 virus, has direct implications for mitigation efforts with respect to clinical practice, non-pharmaceutical interventions, and the prioritisation of risk groups for targeted vaccine delivery. The IFR is also a crucial parameter in COVID-19 dynamic transmission models, providing a way to convert a population's mortality rate into an estimate of infections.MethodsWe estimated age-specific and all-age IFR by matching seroprevalence surveys to total COVID-19 mortality rates in a population. The term total COVID-19 mortality refers to an estimate of the total number of deaths directly attributable to COVID-19. After applying exclusion criteria to 5131 seroprevalence surveys, the IFR analyses were informed by 2073 all-age surveys and 718 age-specific surveys (3012 age-specific observations). When seroprevalence was reported by age group, we split total COVID-19 mortality into corresponding age groups using a Bayesian hierarchical model to characterise the non-linear age pattern of reported deaths for a given location. To remove the impact of vaccines on the estimated IFR age pattern, we excluded age-specific observations of seroprevalence and deaths that occurred after vaccines were introduced in a location. We estimated age-specific IFR with a non-linear meta-regression and used the resulting age pattern to standardise all-age IFR observations to the global age distribution. All IFR observations were adjusted for baseline and waning antibody-test sensitivity. We then modelled age-standardised IFR as a function of time, geography, and an ensemble of 100 of the top-performing covariate sets. The covariates included seven clinical predictors (eg, age-standardised obesity prevalence) and two measures of health system performance. Final estimates for 190 countries and territories, as well as subnational locations in 11 countries and territories, were obtained by predicting age-standardised IFR conditional on covariates and reversing the age standardisation.FindingsWe report IFR estimates for April 15, 2020, to January 1, 2021, the period before the introduction of vaccines and widespread evolution of variants. We found substantial heterogeneity in the IFR by age, location, and time. Age-specific IFR estimates form a J shape, with the lowest IFR occurring at age 7 years (0·0023%, 95% uncertainty interval [UI] 0·0015–0·0039) and increasing exponentially through ages 30 years (0·0573%, 0·0418–0·0870), 60 years (1·0035%, 0·7002–1·5727), and 90 years (20·3292%, 14·6888–28·9754). The countries with the highest IFR on July 15, 2020, were Portugal (2·085%, 0·946–4·395), Monaco (1·778%, 1·265–2·915), Japan (1·750%, 1·302–2·690), Spain (1·710%, 0·991–2·718), and Greece (1·637%, 1·155–2·678). All-age IFR varied by a factor of more than 30 among 190 countries and territories. After age standardisation, the countries with the highest IFR on July 15, 2020, were Peru (0·911%, 0·636–1·538), Portugal (0·850%, 0·386–1·793), Oman (0·762%, 0·381–1·399), Spain (0·751%, 0·435–1·193), and Mexico (0·717%, 0·426–1·404). Subnational locations with high IFRs also included hotspots in the UK and southern and eastern states of the USA. Sub-Saharan African countries and Asian countries generally had the lowest all-age and age-standardised IFRs. Population age structure accounted for 74% of logit-scale variation in IFRs estimated for 39 in-sample countries on July 15, 2020. A post-hoc analysis showed that high rates of transmission in the care home population might account for higher IFRs in some locations. Among all countries and territories, we found that the median IFR decreased from 0·466% (interquartile range 0·223–0·840) to 0·314% (0·143–0·551) between April 15, 2020, and Jan 1, 2021.InterpretationEstimating the IFR for global populations helps to identify relative vulnerabilities to COVID-19. Information about how IFR varies by age, time, and location informs clinical practice and non-pharmaceutical interventions like physical distancing measures, and underpins vaccine risk stratification. IFR and mortality risk form a J shape with respect to age, which previous research, such as that by Glynn and Moss in 2020, has identified to be a common pattern among infectious diseases. Understanding the experience of a population with COVID-19 mortality requires consideration for local factors; IFRs varied by a factor of more than 30 among 190 countries and territories in this analysis. In particular, the presence of elevated age-standardised IFRs in countries with well resourced health-care systems indicates that factors beyond health-care capacity are important. Potential extenuating circumstances include outbreaks among care home residents, variable burdens of severe cases, and the population prevalence of comorbid conditions that increase the severity of COVID-19 disease. During the pre-vaccine period, the estimated 33% decrease in median IFR over 8 months suggests that treatment for COVID-19 has improved over time. Estimating IFR for the pre-vaccine era provides an important baseline for describing the progression of COVID-19 mortality patterns.FundingBill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom

Bimodal Targeting of Human Leukocytes by Fc- and CpG-Decorated Polymersomes to Tune Immune Induction.

The use of well-defined nanovesicles composed of amphiphilic block copolymers (polymersomes) for delivery of adjuvants and antigens is a promising strategy for vaccine development. However, the potency of nanoparticle vaccines depends on efficient interaction with and activation of cells involved in antigen presentation, which can be achieved by targeting cellular receptors. Here, we showed that the Fc fragment display on the polymersome surface resulted in markedly improved interactions with granulocytes, monocytes, and NK cells, while for “naked” polymersomes, virtually no binding to leukocytes was observed. Moreover, CpG-decorated polymersomes were found to also interact with T and/or B cells. Interestingly, whole blood stimulations with Fc fragment and CpG-decorated polymersomes induced interleukin (IL)-6, IL-8, and TNF-α production, while naked polymersomes did not induce any cytokine production. In conclusion, specific immune induction by polymersomes can be controlled using bimodal targeting of different immune receptors, which is an essential feature for targeted vaccine delivery.

Nanotechnology Integration for SARS-CoV-2 Diagnosis and Treatment: An Approach to Preventing Pandemic.

The SARS-CoV-2 outbreak is the COVID-19 disease, which has caused massive health devastation, prompting the World Health Organization to declare a worldwide health emergency. The corona virus infected millions of people worldwide, and many died as a result of a lack of particular medications. The current emergency necessitates extensive therapy in order to stop the spread of the coronavirus. There are various vaccinations available, but no validated COVID-19 treatments. Since its outbreak, many therapeutics have been tested, including the use of repurposed medications, nucleoside inhibitors, protease inhibitors, broad spectrum antivirals, convalescence plasma therapies, immune-modulators, and monoclonal antibodies. However, these approaches have not yielded any outcomes and are mostly used to alleviate symptoms associated with potentially fatal adverse drug reactions. Nanoparticles, on the other hand, may prove to be an effective treatment for COVID-19. They can be designed to boost the efficacy of currently available antiviral medications or to trigger a rapid immune response against COVID-19. In the last decade, there has been significant progress in nanotechnology. This review focuses on the virus’s basic structure, pathogenesis, and current treatment options for COVID-19. This study addresses nanotechnology and its applications in diagnosis, prevention, treatment, and targeted vaccine delivery, laying the groundwork for a successful pandemic fight.

Site-specific MOF-based immunotherapeutic nanoplatforms via synergistic tumor cells-targeted treatment and dendritic cells-targeted immunomodulation

An efficient antitumor immune response relies on multiple cells-based process including tumor cells-targeted immunogenicity increment, dendritic cells (DCs)-targeted vaccine delivery and T cells-mediated tumor elimination. Only limited immune efficacy could be achieved by strengthening the function of single type of cells. Therefore, building an effective immunotherapeutic nanoplatform by simultaneously modulating the functions of multiple cells involved in immune process is urgently demanded. However, it is challenging to modulate multiple cells since the on-demand delivery of diverse agents to different cells is restricted by inherent different target sites. Herein, as a proof of concept, dual tailor-made metal organic framework (MOF) nanoparticles based on zeolitic imidazolate framework-8 (ZIF-8) are designed to comprehensively enhance the immunotherapy via the spatiotemporal cooperation of various therapeutic agents including photothermal agent IR820, adjuvant imiquimod (R837) and immunomodulator 1-methyl-d-tryptophan (1 MT). On one hand, IR820@ZIF-8 is modified with hyaluronic acid for realizing tumor-targeted photothermal therapy, accompanied with the release of tumor antigens. On the other hand, (R837+1 MT)@ZIF-8 is modified with mannan for achieving DCs-targeted immune amplification. The synergistic tumor cells-targeted treatment and DCs-targeted immunomodulation can efficiently overcome two major obstacles in immunotherapy: inadequate activation of immune response and immune evasion, offering powerful platform against invasive malignancy and rechallenged tumors.

Mannosylated chitosan nanoparticles loaded with FliC antigen as a novel vaccine candidate against Brucella melitensis and Brucella abortus infection

Brucellosis is a worldwide bacterial zoonosis disease. Live attenuated Brucella vaccines have several drawbacks. Thus development of a safe and effective vaccine for brucellosis is a concern of many scientists. FliC protein contributes in virulence of Brucella; hence, it is a promising target for brucellosis vaccine. In this study, Mannosylated Chitosan Nanoparticles (MCN) loaded with FliC protein were synthesized as a targeted vaccine delivery system. The immunogenicity and protective efficacy of FliC and FliC-MCN against Brucella infection were evaluated in BALB/c mice. After cloning, expression and purification, FliC protein was loaded on MCN. The particle size, loading efficiency and in vitro release of the NPs were determined. Our investigation revealed that FliC and FliC-MCN could significantly increase specific IgG response (higher IgG2a titers). Besides, spleen cells from immunized mice produced high level of IFN-γ and IL-2 and low level IL-10 cytokines. Immunization with FliC and FliC-MCN conferred significant degree of protection against B. melitensis 16 M and B. abortus 544 infections. Overall these results indicate that FliC protein would be a novel potential antigen candidate for the development of a subunit vaccine against B. melitensis and B. abortus. Moreover, MCN could be used as an adjuvant and targeted vaccine delivery system.

Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium

Targeting a vaccine to the mucosal surface has recently been recognized as a promising approach to efficiently induce mucosal immune responses against enteric pathogens. However, poor uptake and inefficient transport of orally delivered subunit vaccines across the intestinal epithelium combined with weak immune responses still present important bottlenecks for mucosal vaccination. A possible strategy suggested to surmount these hurdles is to target the selected antigen to transcytotic receptors, such as aminopeptidase N (APN) present on enterocytes and antigen-presenting cells (APCs). Therefore, we aimed to identify potent and selective VHHs against porcine aminopeptidase N (pAPN), that were fused to the fragment crystallizable (Fc) domain of the murine IgG2a, resulting in dimeric VHH-MG fusions. Out of a library of 30 VHH-MG fusion candidates, two fusions displaying the best binding on pAPN-expressing cells were selected and showed in vivo internalization across the porcine gut epithelium. One of these fusions triggered systemic and intestinal IgA responses upon oral administration. Our results demonstrate the potential of bivalent VHH-MG fusions as delivery vehicles for vaccine antigens. VHH-mediated targeting of antigens to APN to generate protective immunity at the mucosal surface remains to be further validated.

Tạo dòng, biểu hiện và tái gấp cuộn prion protein (PrPc) chuột dung hợp với GST

Oral vaccine is one of the most potential strategies for gastrointestinal infection due to significant advantages over parenteral vaccines. In order to overcome exsiting hurdles in oral vaccine, namely oral tolerance and antigen dispersion, gut-associated M cell is a target for vaccine delivery. Cellular prion protein (PrPC), an M cell receptor, was experimentally proven to interact with heat shock protein Hsp60. In the previous in sillico studies, two Hsp60-deprived peptides have been predicted to be key-players in this interaction. Therefore, providing PrPC for in vitro binding assay with Hsp60 is desired to confirm the binding activity of the two predicted peptides. In this study, murine PrPC-encoding gene (mPrPc) was cloned into pET-gst to generate recombinant vector namedly pET-gst-mPrPc. Next, the vector was transformed into expression host Escherichia coli (E. coli) BL21 (DE3) for protein expression. SDS-PAGE and Western blot probed with anti-GST antibodies showed the protein expressed in inclusion bodies and hence was subsequently solubilized and refolded. After refolding, GST-mPrPC protein was harvested in soluble form with the refolding efficiency reached 88.33%.

The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery.

Nanocarriers (NC) are very promising tools for cancer immunotherapy. Whereas conventional vaccines are based on the administration of an antigen and an adjuvant in an independent fashion, nanovaccines can facilitate cell-specific co-delivery of antigen and adjuvant. Furthermore, nanovaccines can be decorated on their surface with molecules that facilitate target-specific antigen delivery to certain antigen-presenting cell types or tumor cells. However, the target cell-specific uptake of nanovaccines is highly dependent on the modifications of the nanocarrier itself. One of these is the formation of a protein corona around NC after in vivo administration, which may potently affect cell-specific targeting and uptake of the NC. Understanding the formation and composition of the protein corona is, therefore, of major importance for the use of nanocarriers in vaccine approaches. This Mini Review will give a short overview of potential non-specific interactions of NC with body fluids or cell surfaces that need to be considered for the design of NC vaccines for immunotherapy of cancer.

Development and physicochemical, toxicity and immunogenicity assessments of recombinant hepatitis B surface antigen (rHBsAg) entrapped in chitosan and mannosylated chitosan nanoparticles: as a novel vaccine delivery system and adjuvant

In this study chitosan nanoparticles (CS NPs) and mannosylated chitosan nanoparticles (MCH NPs) loaded with recombinant hepatitis B surface antigen (rHBsAg) was synthesized as a vaccine delivery system and assessed toxically and immunologically. The physicochemical properties of the nanoparticles (NPs) were determined by methods including scanning electron microscope (SEM) and dynamic light scattering (DLS). The morphology of the NPs was semi spherical and the average diameter of the loaded CS and MCH NPs was found to be 189 and 239 nm, respectively. The release studies showed that after the initial burst, both of the loaded NPs provided a continuous and slow release of the antigens. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed concentration and time dependent toxicity profile for both formulations, but rHBsAg loaded CS nanoparticle showed higher toxicity due to smaller particle size and larger zeta potential. Abnormal toxicity test (ATT) results showed no signs of toxicity in mice and guinea-pigs treated with loaded MCHNPs. Stability test for six months showed acceptable changes in size, surface charge, and antigenicity for loaded MCH nanoparticles. Finally, in vivo immunogenicity study revealed greater adjuvant capability of MCH nanoparticles than others formulations. Our results showed MCH NPs can be used as a controlled and targeted vaccine delivery system.

Novel approach to improve vaccine immunogenicity: Mannosylated chitosan nanoparticles loaded with recombinant hepatitis B antigen as a targeted vaccine delivery system

The design of effective vaccine delivery system is opening up new feasibilities for making immunization more safe and efficient. In this study, recombinant hepatitis B virus surface antigen (rHBsAg) was loaded in mannosylated chitosan (MC) nanoparticles to be used as a targeted vaccine delivery vehicles. The nanoparticles were prepared by ionic gelation method and characterized for physicochemical properties, cytotoxicity and antigenicity. The rHBsAg-loaded MC nanoparticles showed spherical shape with mean particle size of 246 ± 33 nm, zeta potential of 25.6 ± 1.7 mV, loading capacity of 12.2 ± 1.4%, and encapsulation efficiency of 90 ± 1.6%. In vitro release profile of rHBsAg-loaded MC nanoparticles exhibited an initial burst release of about 26% in the first 7 days followed by a slow release of 25% for 49 days, with release kinetic similar to Higuchi model. SDS-PAGE analysis confirmed integrity of released rHBsAg and structural stability of the antigen during entrapment process. The rHBsAg-loaded MC nanoparticles indicated time-and concentration-dependent cytotoxicity using MTT assay. It can be concluded that entrapment of rHBsAg in MC nanoparticles appears to be a suitable approach for targeting this antigen into body immune system.

Antigen-presenting cell-targeted lentiviral vectors do not support the development of productive T-cell effector responses: implications for in vivo targeted vaccine delivery.

Targeting transgene expression specifically to antigen-presenting cells (APCs) has been put forward as a promising strategy to direct the immune system towards immunity. We developed the nanobody-display technology to restrict the tropism of lentiviral vectors (LVs) to APCs. However, we observed that immunization with APC-targeted LVs (DC2.1-LVs) did not evoke strong antigen-specific T-cell immunity when compared to immunization with broad tropism LVs (VSV.G-LVs). In this study, we report that VSV.G-LVs are more immunogenic than DC2.1-LVs because they transduce stromal cells, which has a role in activating antigen-specific T cells. Moreover, VSV.G-LVs trigger a pro-inflammatory innate immune response through transduction of APCs and stromal cells, while DC2.1-LVs trigger a type I interferon response with anti-viral capacity. These findings question the rationale of targeting LVs to APCs and argue for the development of VSV.G-LVs with an improved safety profile.

Cellular requirements for systemic control of Salmonella enterica serovar Typhimurium infections in mice.

The rational design of vaccines requires an understanding of the contributions of individual immune cell subsets to immunity. With this understanding, targeted vaccine delivery approaches and adjuvants can be developed to maximize vaccine efficiency and to minimize side effects (S. H. E. Kaufmann et al., Immunity 33:555-577, 2010; T. Ben-Yedidia and R. Arnon, Hum. Vaccines 1:95-101, 2005). We have addressed the contributions of different immune cell subsets and their ability to contribute to the control and clearance of the facultative intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) in a murine model. Using a systematic and reproducible model of experimental attenuated S. Typhimurium infection, we show that distinct lymphocyte deficiencies lead to one of four different infection outcomes: clearance, chronic infection, early death, or late death. Our study demonstrates a high level of functional redundancy in the ability of different lymphocyte subsets to provide interferon gamma (IFN-γ), a critical cytokine in Salmonella immunity. Whereas early control of the infection was entirely dependent on IFN-γ but not on any particular lymphocyte subset, clearance of the infection critically required CD4(+) T cells but appeared to be independent of IFN-γ. These data reinforce the idea of a bimodal immune response against Salmonella: an early T cell-independent but IFN-γ-dependent phase and a late T cell-dependent phase that may be IFN-γ independent.

TLR3-responsive, XCR1+, CD141(BDCA-3)+/CD8α+-equivalent dendritic cells uncovered in healthy and simian immunodeficiency virus-infected rhesus macaques.

In mice, CD8α(+) myeloid dendritic cells (mDC) optimally cross-present Ags to CD8(+) T cells and respond strongly to TLR3 ligands. Although equivalent DC have been identified by comparative genomic analysis and functional studies in humans as XCR1(+)CD141 (BDCA-3)(+)Clec9A(+)cell adhesion molecule 1(+) mDC, and in sheep as CD26(+) mDC, these cells remained elusive in nonhuman primates. To remedy this situation, we delineated precisely DC and monocyte populations by 12-color flow cytometry and transcriptomic analyses in healthy rhesus macaques. We identified a new mDC population, with strong phenotypic and transcriptional homology to human CD141(+) and murine CD8α(+) mDC, including XCR1 membrane expression as a conserved specific marker. In contrast, high CD11c expression was not characteristic of mDC in macaques, but of CD16(+) monocytes. Like their human and murine homologs, simian XCR1(+) mDC had much stronger responses to TLR3 stimulation than other myeloid cells. The importance of this new mDC population was tested in SIV(mac251) infection, the most relevant animal model for pathogenic HIV-1 infection and vaccination. This population increased sharply and transiently during acute infection, but was reduced in blood and spleen during advanced disease. The identification of XCR1(+) mDC in rhesus macaques opens new avenues for future preclinical vaccinal studies and highlights XCR1 as a prime candidate for targeted vaccine delivery.

Vaccine and Needle-Free Vaccination Delivery System

Needle-free injection delivery system is a new method use a unique profile to deliver vaccine to the proper tissue depth for injection. The shift from needle-based to needle-free immunization is also catalyzed, in part, by the realization that skin, which can increase vaccine immunogenicity, is ideal target for vaccine delivery. As a promising delivery of vaccines system, it has the potential to decrease the dose of vaccine antigen, enhance immune response and may furthermore help to reduce costs.

Internalization of Poly(dG)-antigens by dendritic cells (106.14)

Abstract Effective vaccine design depends in part on the ability to target specific antigens (Ag) to Ag presenting cells (APCs), including dendritic cells (DCs). Further, to generate effective antitumor and antiviral immunity, vaccine platforms should enable efficient MHC class I and class II restricted antigen processing leading to synergistic CD4 and CD8 T-cell responses. To facilitate targeted vaccine delivery, we have developed Poly(dG)-protein Ags. These Ag conjugates have the potential to greatly increase vaccine efficiency by inducing spontaneous aggregation of Ag into particulate complexes with intrinsic adjuvant function. The resulting particulate structure includes exposed phosphate groups with affinity for scavenger receptors expressed by APCs. We have successfully conjugated Poly(dG) residues to the model Ag ovalbumin (OVA) and found that Poly(dG)-OVA can be rapidly endocytosed, and efficiently presented to class II-restricted T cells, and cross-presented to class I-restricted T cells in vitro and in vivo. We compared DCs internalization of Poly(dG) conjugated and unconjugated Ag using confocal microscopy and found that Poly(dG)-OVA bound to the cell surface of DCs with higher affinity and was internalized several times more efficiently than Ag alone. These results suggest that coupling Poly(dG) to Ags enables efficient APCs targeting. Understanding the mechanisms of internalization, processing, and presentation of Poly(dG)-Ags will contribute to future vaccine design.

Dry-coated microprojection array patches for targeted delivery of immunotherapeutics to the skin

Dry-coated microprojections (MPs) deliver vaccine to abundant immunogenic cells within the skin to induce immune responses. Success in this targeted vaccine delivery relies on overcoming the challenges of dry-coating the vaccine onto the very small (≤ 90 µm length) and densely packed (~ 20,000 cm − 2 ) MPs. In this paper, we show that a gas-jet drying coating method achieves the desired uniform coating. The coating approach is robustly demonstrated on compounds representative of a range of immunotherapeutics (e.g. DNA, proteins), with each uniformly coated on thousands of MPs. Furthermore, the dry-coating remains intact during skin insertion, and then releases within the wet skin cellular environment within 3 min. Finally, we applied ovalbumin protein coated MP patches to immunise mice, achieving comparable antibody levels ( p = 0.08) with needle and syringe intramuscular injection. In summary, this paper presents a simple, practical and versatile method to achieve uniform coating on very small and densely packed MPs for a needle-free and targeted vaccine delivery technology.