Cold Chain Storage Research Articles

Dissipation behavior, residue dynamics, and dietary risk assessment of forchlorfenuron in postharvest kiwifruits during simulated cold chain logistics and store shelf life.

Forchlorfenuron (CPPU) is often applied during the cultivation of kiwifruit to produce larger fruit. To address degradation patterns of CPPU during simulated cold chain logistics and simulated shelf life of the fruit after harvest, appropriate storage methods and safe consumption behavior can be investigated. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry method was adopted to detect CPPU residues under different conditions. CPPU in kiwifruit stored at 6°C had a half-life of 40.8-77.0days. However, when kiwifruit was stored at 0°C under simulated cold chain storage conditions, the half-life of CPPU was 63.0-115.5days, implying that lower storage temperatures can reduce the degradation rate of CPPU. The residues of CPPU in kiwifruit pulp declined with time, and the reduction followed the first-order kinetics equation. More CPPU residues were present in the pulp of postharvest kiwifruit treated with exogenous ethylene than in the pulp of untreated kiwifruit. Thus, using exogenous ethylene for artificial ripening after harvest is not recommended. We determined that the appropriate cold chain storage temperature is 6°C. It is recommended that the public select kiwifruit stored for at least 2weeks. The estimated chronic and acute dietary risk quotients of CPPU are ≤ 0.79% and ≤ 0.11%, respectively. Therefore, it is highly unlikely that consumers will be poisoned by CPPU due to kiwifruit consumption. Our results provide scientific evidence regarding the adoption of appropriate kiwifruit storage methods and consumption behavior to enhance consumption safety.

A公司医药冷链仓储存在的问题和对策分析

A公司医药冷链仓储存在的问题和对策分析

COVID-19 vaccine and the cold chain implications for global adoption.

The COVID-19 pandemic has spread globally with 190.8 million infected cases and 4.1 million deaths as of July 18, 2021. In absence of any definite antiviral agent availability and therapeutic armamentarium, vaccines are considered critical. While 20 vaccines are in use, about 295 vaccines are underdevelopment globally using eleven technological platforms. While the vaccines have >80% efficacy, the ultracold (-70°C and -20°C) storage and logistics requirements for some raise concerns for implementation, especially in developing countries. The Ebola vaccination in African countries, which required an ultracold chain provided lessons for these COVID-19 vaccines. The existing vaccine cold chain system suffers from temperature excursions at cold chain stores and during transportations in different countries suggests careful assessment and addressing the gaps for effective vaccine introduction. Appropriate attention for cold chain storage, logistics (especially the last mile), and vaccine management and upgradation is needed to achieve optimal vaccine effectiveness for curtailing the pandemic.

Technology and Equipment for Cold-Chain Storage and Transportation of Fresh Agricultural Products

Technology and Equipment for Cold-Chain Storage and Transportation of Fresh Agricultural Products

Chilling injury in pineapple fruits: physical quality attributes and antioxidant enzyme activity

Harvested fruit have high metabolic and moisture content which leads to an active biochemical reaction that contributes to decrement of nutritional value such as vitamin, proteins and lipids. The application of low temperature as a single-effective management to prolong shelf-life of fruits is a common practice which applied to keep agriculture commodities at high quality. A matured stage pineapple is very perishable and cold storage chain is crucial in maintaining the chemical and physical quality attributes in order to assure its commercial value for market. The main objective of this study is to evaluate the effect of sub-optimum cold storage scenario on changes of pineapple fruits physical quality attributes, the activity of browning enzyme and antioxidant related enzyme in 2 pineapple cultivars (cv.), Morris (Queen-type) and Josapine (hybrid of Spanish and Smooth Cayeen). Malaysian pineapple fruit cv. with different sensitivity toward CI, Morris (Queen-type) and Josapine (Smooth-Cayenne-type) were stored at sub-optimal storage temperatures (4±2°C) for 28 days to investigate the effects of CI towards physical quality attributes and antioxidant enzyme activity. The result indicated both cv. was affected with CI towards the 28 days of sub-optimum cold storage. Overall physical quality attributes indicated CI was found positively correlated with the increase of EL and TTA and on the contrary decrease its firmness, weight (% w/w), brightness (L*) and redness (A*). Similarly, a positive correlation was also deduced between CI symptoms and the activities of PPO and APX which reflect the incident of oxidative stress. The results derived from this study may serve as a basis for evaluation of better postharvest strategies to control CI during cold chain storage of pineapple fruits and thus assure the quality and nutritional value till it reaches to consumer.

Applications of Nanovaccines for Disease Prevention in Cattle.

Vaccines are one of the most important tools available to prevent and reduce the incidence of infectious diseases in cattle. Despite their availability and widespread use to combat many important pathogens impacting cattle, several of these products demonstrate variable efficacy and safety in the field, require multiple doses, or are unstable under field conditions. Recently, nanoparticle-based vaccine platforms (nanovaccines) have emerged as promising alternatives to more traditional vaccine platforms. In particular, polymer-based nanovaccines provide sustained release of antigen payloads, stabilize such payloads, and induce enhanced antibod- and cell-mediated immune responses, both systemically and locally. To improve vaccine administrative strategies and efficacy, they can be formulated to contain multiple antigenic payloads and have the ability to protect fragile proteins from degradation. Nanovaccines are also stable at room temperature, minimizing the need for cold chain storage. Nanoparticle platforms can be synthesized for targeted delivery through intranasal, aerosol, or oral administration to induce desired mucosal immunity. In recent years, several nanovaccine platforms have emerged, based on biodegradable and biocompatible polymers, liposomes, and virus-like particles. While most nanovaccine candidates have not yet advanced beyond testing in rodent models, a growing number have shown promise for use against cattle infectious diseases. This review will highlight recent advancements in polymeric nanovaccine development and the mechanisms by which nanovaccines may interact with the bovine immune system. We will also discuss the positive implications of nanovaccines use for combating several important viral and bacterial disease syndromes and consider important future directions for nanovaccine development in beef and dairy cattle.

Optimization of UC-MSCs cold-chain storage by minimizing temperature fluctuations using an automatic cryopreservation system

The effective long-term cryopreservation of human mesenchymal stem cells is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Off-the-shelf availability of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) for regenerative medicine application requires the development of nontoxic, safe, and efficient protocols for cryopreservation. In the long-term low-temperature storage process of cells, traditional manual storage has a great impact on cell activity, recovery, and function due to repeated exposure of cells to room temperature. To minimize the effect of fluctuation in ambient temperature on stored cells, we designed an automatic cryopreservation system that handles cells under controlled temperatures. In this work, UC-MSCs were utilized to investigate and compare the influence of manual and automatic cryopreservation approaches. To simulate the manual process, the UC-MSCs were transferred back and forth repeatedly (up to 400 times) between the liquid nitrogen (LN2) tank (−150 °C) and room temperature by a robotic arm. Similarly, the UC-MSCs from the same batch were collected and transferred repeatedly between two storage units by the automatic cryopreservation system, where the cells were maintained below-150 °C throughout the cold chain process. Viability, percent recovery, adherence capability, cell proliferation, and multilineage differentiation ability were assessed for UC-MSCs. Compared to the manual approach, UC-MSCs handled by the automatic system demonstrated higher viability, percent recovery, and cell proliferation, as well as improved adherence to culture plate with greater potential in multilineage differentiation after 400 temperature cycles. The described entire cold chain system may provide a powerful tool to develop safe, reliable and efficient protocols for manufacturing and banking of UC-MSCs, improving their off-the-shelf availability for regenerative medicine applications.

Fully synthetic injectable depots with high drug content and tunable pharmacokinetics for long-acting drug delivery

Clinical studies have validated that antiretroviral (ARV) drugs can serve as an HIV pre-exposure prophylactic (PrEP) strategy. Dosing adherence remains a crucial factor determining the final efficacy outcomes, and both long-acting implants and injectable depot systems are being developed to improve patient adherence. Here, we describe an injectable depot platform that exploits a new mechanism for both formation and controlled release. The depot is a polymeric prodrug synthesized from monomers that incorporate an ARV drug tenofovir alafenamide (TAF) with degradable linkers that can be designed to control release rates. The prodrug monomers are synthetically incorporated into homopolymer or block designs that exhibit high drug weight percent (wt%) and also are hydrophobized in these prodrug segments to drive depot formation upon injection. Drug release converts those monomers to more hydrophilic pendant groups via linker cleavage, and as this drug release proceeds, the polymer chains losing hydrophobicity are then disassociated from the depot and released over time to provide a depot dissolution mechanism. We show that long-acting TAF depots can be designed as block copolymers or as homopolymers. They can also be designed with different linkers, for example with faster or slower degrading p-hydroxybenzyloxycarbonyl (Benzyl) and ethyloxycarbonyl (Alkyl) linkers, respectively. Diblock designs of p(glycerol monomethacrylate)-b-p(Alkyl-TAF-methacrylate) and p(glycerol monomethacrylate)-b-p(Benzyl-TAF-methacrylate) were first characterized in a mouse subcutaneous injection model. The alkylcarbamate linker design (TAF 51 wt%) showed excellent sustained release profiles of the key metabolite tenofovir (TFV) in skin and plasma over a 50-day period. Next, the homopolymer design with a high TAF drug wt% of 73% was characterized in the same model. The homopolymer depots with p(Alkyl-TAFMA) exhibited sustained TFV and TAF release profiles in skin and blood over 60 days, and TFV-DP concentrations in peripheral blood mononuclear cells (PBMC) were found to be at least 10-fold higher than the clinically suggested minimally EC90 protective concentration of 24 fmol/106 cells. These are the first reports of sustained parent TAF dosing observed in mouse and TFV-DP in mouse PBMC. IVIS imaging of rhodamine labeled homopolymer depots showed that degradation and release of the depot coincided with the sustained TAF release. Finally, these polymers showed excellent stability in accelerated stability studies over a six-month time period, and exceptional solubility of over 700 mg/mL in the DMSO formulation solvent. The homopolymer designs have a drug reservoir potential of well over a year at mg/day dosing and may not require cold chain storage for global health and developed world long-acting drug delivery applications.

Effects of delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots

To explore effects of different delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots (DBS), so as to provide evidence for improving accurate and reliable detection by tandem mass spectrometry. A total of 1 254 616 newborn DBS samples in Newborn Screening Center of Zhejiang Province were delivered and stored at room temperature (group A, n=338 467), delivered by cold-chain logistics system and stored at low temperature (group B, n=480 021), or delivered by cold-chain logistics system and stored at low temperature and low humidity (group C, n= 436 128), respectively. The concentrations of amino acids and carnitines in DBS were detected by tandem mass spectrometry. Data analysis was performed by SPSS 24.0 to explore the influence of temperature and humidity on the concentrations of amino acids and carnitines. The concentrations of amino acids and carnitines in the three groups were skewed, and the differences in amino acid and carnitine concentrations among groups were statistically significant (all P<0.01). The median concentration of tyrosine was lower in group A than those in group B and group C by 18%and 16%respectively, while there was no significant difference between the last two groups. The median concentrations of methionine were lower in group A and group B than that in group C by 15%and 11%, respectively. The median concentrations of arginine were lower in group A and group B than that in group C by 12%and 25%, respectively. The median concentration of free carnitine (C0) was higher in group A than that in group C by 12%, while there was no significant difference between group A and group B. The median concentrations of acetylcarnitine (C2), propionyl carnitine (C3), C3DC+C4OH, C5DC+C6OH and hexadecanoyl carnitine (C16) were lower in group A than those in group B and group C by 21%-64%. The concentrations of other amino acids and acylcarnitines differed little among three groups. The monthly median coefficients of variation of other amino acids and carnitines in group A were higher than those in group B and group C except for citrulline, C4DC+C5OH and isovalerylcarnitine (C5). Cold-chain logistics system and storage in low temperature and low humidity can effectively reduce degradation of some amino acids and carnitines in DBS, improve the accuracy and reliability of detection, and thus ensures the quality of screening for neonatal metabolic diseases.

Thermally buffering polyethylene/halloysite/phase change material nanocomposite packaging films for cold storage of foods

Abstract Nanocomposite flexible food packaging films that prolong the time that frozen or chilled food products stay cold are demonstrated. Nanohybrids of phase change materials (PCMs) and halloysite nanotubes (HNTs) were prepared as nanofillers with thermal buffering performance. HNTs were impregnated with polymeric PCMs, PEG400 and PEG600, resulting in a mixture of form-stable HNT/PCM nanohybrids that presented consecutive melting transitions in the temperature range of −22 °C – 22 °C. The incorporation of the mixture of HNT/PEG400 and HNT/PEG600 nanonybrids into polyethylene (PE) matrix by melt compounding resulted in flexible nanocomposite films that have acceptable mechanical properties for use in food packaging applications and presented a broad melting transition from −17 °C to 26 °C with a latent heat of 2.3 J/g. The thawing rate of frozen nanocomposite films at room temperature was less than half of the thawing rate of neat PE films. Furthermore, nanocomposite films delayed the warming of frozen and chilled samples for 18 min and 20 min, respectively, relative to neat PE films. Nanocomposite films composed of PCM impregnated HNTs demonstrated here are the first examples of flexible food packaging films with significant thermal buffering capacity in cold chain temperatures and have a great potential to enhance food quality and food safety in cold-chain storage and transportation.

Preservation of Quaternary Structure in Thermostable, Lyophilized Filovirus Glycoprotein Vaccines: A Search for Stability-Indicating Assays

The filoviruses Zaire ebolavirus (EBOV), Marburg marburgvirus (MARV), and Sudan ebolavirus (SUDV) are some of the most lethal infectious agents known. To date, the Zaire ebolavirus vaccine (ERVEBO®) is the only United States Food and Drug Administration (FDA) approved vaccine available for any species of filovirus. However, the ERVEBO® vaccine requires cold-chain storage not to exceed −60 °C. Such cold-chain requirements are difficult to maintain in low- and middle-income countries where filovirus outbreaks originate. To improve the thermostability of filovirus vaccines in order to potentially relax or eliminate these cold-chain requirements, monovalent subunit vaccines consisting of glycoproteins from EBOV, MARV, and SUDV were stabilized within amorphous disaccharide glasses through lyophilization. Lyophilized formulations and liquid controls were incubated for up to 12 weeks at 50 °C to accelerate degradation. To identify a stability-indicating assay appropriate for monitoring protein degradation and immunogenicity loss during these accelerated stability studies, filovirus glycoprotein secondary, tertiary, and quaternary structures and vaccine immunogenicity were measured. Size-exclusion chromatography was the most sensitive indicator of glycoprotein stability in the various formulations for all three filovirus immunogens. Degradation of the test vaccines during accelerated stability studies was reflected in changes in quaternary structure, which were discernible with size-exclusion chromatography. Filovirus glycoproteins in glassy lyophilized formulations retained secondary, tertiary, and quaternary protein structure over the incubation period, whereas the proteins within liquid controls both aggregated to form higher molecular weight species and dissociated from their native quaternary structure to form a variety of structurally-perturbed lower molecular weight species.

Controlling Human Rabies: The Development of an Effective, Inexpensive and Locally Made Passive Cooling Device for Storing Thermotolerant Animal Rabies Vaccines.

Thermotolerant vaccines greatly improved the reach and impact of large-scale vaccination programs to eliminate diseases such as smallpox, polio and rinderpest. A recent study demonstrated that the potency of the Nobivac® Canine Rabies vaccine was not impacted following experimental storage at 30 °C for three months. We conducted a study to develop a passive cooling device (PCD) that could store thermotolerant vaccines under fluctuating subambient temperatures. Through a participatory process with local communities in Northern Tanzania, we developed innovative PCD designs for local manufacture. A series of field experiments were then carried out to evaluate the effectiveness of five PCDs for vaccine storage under varying climatic conditions. Following iterative improvement, a final prototype “Zeepot Clay” was developed at the cost of US$11 per unit. During a further field-testing phase over a 12-month period, the internal temperature of the device remained below 26 °C, despite ambient temperatures exceeding 42 °C. Our study thus demonstrated that locally designed PCDs have utility for storing thermotolerant rabies vaccines at subambient temperatures. These results have application for the scaling up of mass dog vaccination programs in low-and-middle income countries, particularly for hard-to-reach populations with limited access to power and cold-chain vaccine storage.

Revaccination management of a large cohort of pediatric patients following a potential lapse in cold storage

IntroductionIn a pediatric clinic in California (US), 3823 patients were vaccinated with potentially-compromised vaccines following lapses in cold storage chain management between February 2014 and April 2015. A revaccination program was initiated in May 2015. Families were contacted by mail and encouraged to discuss follow-up options with their care team, namely: revaccination, serological testing and/or revaccination, or no further action. This study aimed: to understand which families were more likely to respond to the outreach, and to engage in any testing and/or revaccination; to determine whether or not vaccination with these potentially-compromised vaccines elicited sufficient immune response in pediatric patients; and to estimate the program cost. MethodsPatients who had received potentially-compromised vaccines were identified, and relevant data were extracted from their electronic health records. Logistic regression analyses were performed to identify factors associated with response to outreach, serological testing and/or revaccination. Results3823 patients between 0 and 21 years received an average of 3.1 potentially-compromised vaccines. 2547 revaccinations were performed (1515 patients) and 544 patients had serological testing results. Non-immune titer levels were only reported for 3–4% and 8% of the tested patients who had received potentially-compromised tetanus and hepatitis B vaccines, respectively, and only for children two years old and younger. Three years after the revaccination program started, 77% of all cases were considered resolved and 62.5% of patients (1970/3152) who were administered potentially-compromised vaccines were either revaccinated or had seroprotective titers. Response to outreach and decision to choose serological testing and/or revaccinate were affected by patient age, race/ethnicity and zip code median income (p < 0.05). ConclusionWe observed race/ethnicity, patient age and income differences in response to the outreach and decision-making. For patients vaccinated with potentially-compromised vaccines, serological testing should be considered prior to revaccination. Revaccination may not be the most appropriate course of action for all patients.

Spray dried VSV-vectored vaccine is thermally stable and immunologically active in vivo

Effective vaccine delivery and coverage to rural and resource-poor countries is hindered by the dependence on cold chain storage. As such, developments of cold chain-free technologies are highly sought. Although spray dried adenoviral vectors have shown long term stability at ambient temperatures and relatively low humidity, it remains to be determined whether similar excipient formulations are applicable to other viral vectors. To address this, we have spray dried vesicular stomatitis virus (VSV)-vectors with a panel of well-characterized sugar excipients to determine the optimal formulation for vector stabilization. Upon reconstitution, we show that trehalose conferred superior stability of VSV both in vitro and in vivo. Importantly, following cold chain-free storage at elevated temperatures at 37 °C for 15 days, we show that a VSV-vectored vaccine retains its in vivo immunogenicity, whereas a liquid control completely lost its immune-stimulating ability. Our results provide foundational evidence that spray drying with properly tested excipients can stabilize viral vectors such as VSV, allowing them to be stored long-term at elevated temperatures without dependency on cold chain conditions.

Lyophilized Cell-Free Systems Display Tolerance to Organic Solvent Exposure.

Cell-free systems offer a powerful way to deliver biochemical activity to the field without cold chain storage. These systems are capable of sensing as well as biosynthesis of useful molecules at the point of need. So far, cell-free protein synthesis (CFPS) reactions have been studied as aqueous solutions in test tubes or absorbed into paper or cloth. Embedding biological functionality into broadly used materials, such as plastic polymers, represents an attractive goal. Unfortunately, this goal has for the most part remained out of reach, presumably due to the fragility of biological systems outside of aqueous environments. Here, we describe a surprising and useful feature of lyophilized cell-free lysate systems: tolerance to a variety of organic solvents. Screens of individual CFPS reagents and different CFPS methods reveal that solvent tolerance varies by CFPS reagent composition. Tolerance to suspension in organic solvents may facilitate the use of polymers to deliver dry cell-free reactions in the form of coatings or fibers, or allow dosing of analytes or substrates dissolved in nonaqueous solvents, among other processing possibilities.

The Accuracy of Dried Blood Spots Compared to Plasma or Serum Retinol for the Diagnosis of Vitamin A Deficiency: A DTA Systematic Review and Meta-Analysis

Abstract Objectives Dried blood spots (DBS) do not require a cold chain, making them easier to store and transport compared to serum or plasma samples in resource-limited settings. Our objective was to determine the accuracy of DBS compared to serum or plasma retinol for assessing vitamin A status in individuals and populations. Methods A systematic review of diagnostic test accuracy (DTA) was performed using standard Cochrane Methods for Screening and Diagnostic Tests. All human studies were included if they determined retinol in DBS (index test) and compared results to retinol determined in either plasma or serum samples (reference standard). Index and reference methods could use either capillary or venous blood with retinol quantified by HPLC. We used the WHO threshold of 0.70 μmol/L to define low retinol concentrations. Meta-analysis determined summary estimates of sensitivity and specificity using the bivariate model, which models logit transformed sensitivities and specificities as a bivariate normal distribution including a parameter for the negative correlation between sensitivity and specificity. Rstudio (Version 1.1.456, RStudio, Inc. Boston, MA) was used for analysis. Results Our search (conducted April 10, 2019) identified 9021 records, and 285 studies were assessed in full-text for inclusion; 6 publications reported 8 studies comprising 397 participants, 50 of which had low serum retinol by the reference method. The use of DBS to determine a low retinol level had summary estimates (95% CIs) for sensitivity of 86.7% (71.4 to 94.5) and specificity of 99.5% (89.7 to 100.0). Conclusions Use of DBS to determine low retinol has been shown to have good sensitivity and high specificity compared to serum or plasma. Use of DBS can reduce the need for centrifugation and cold chain for storage and transport. The mixed use of capillary and venous blood in both index and reference methods merits further investigation for the determination of retinol in DBS. Funding Sources None declared.

Long-term stability of microbiome diversity and composition in fecal samples stored in eNAT medium.

Fecal samples collected for microbiome analyses are typically frozen to avoid postcollection changes in microbial composition. eNAT is a guanidine thiocyanate‐based medium that stabilizes microbial DNA and allows safe specimen handling and shipping by inactivating microorganisms. We collected fecal samples (n = 50) from children undergoing hematopoietic stem cell transplantation. We divided samples into three aliquots: (a) stored in RNAlater and immediately transferred to −80°C; (b) stored in eNAT medium and immediately transferred to −80°C; and (c) stored in eNAT medium at ambient temperature (~20°C) for 30 days prior to transfer to −80°C. Mean (standard deviation) Shannon diversity and Chao1 indices in sample aliquots were 2.05 (0.62) and 23.8 (16.6), respectively. Comparing samples frozen immediately in RNAlater to samples frozen immediately in eNAT, there were no differences in Shannon diversity (p = .51), Chao1 richness (p = .66), and overall microbiome composition (p = .99). Comparing eNAT samples frozen immediately to samples stored at ambient temperature, we identified no differences in Shannon diversity (p = .65), Chao1 richness (p = .87), and overall microbiome composition (p = .99). Storage of fecal samples in eNAT at ambient temperature for 30 days did not alter microbiome richness, diversity, or composition. eNAT may be a useful medium for fecal microbiome studies, particularly when cold chain storage is unavailable.

Improved Diabetic Wound Healing by EGF Encapsulation in Gelatin-Alginate Coacervates.

Topical imageplication of epidermal growth fctor (EGF) has been used to accelerate diabetic foot ulcers but with limited efficacy. In this study, we selected a complex coacervate (EGF-Coa) composed of the low molecular weight gelatin type A and sodium alginate as a novel delivery system for EGF, based on encapsulation efficiency and protection of EGF from protease. EGF-Coa enhanced in vitro migration of keratinocytes and accelerated wound healing in streptozotocin-induced diabetic mice with increased granulation and re-epithelialization. While diabetic wound sites without treatment showed downward growth of hyperproliferative epidermis along the wound edges with poor matrix formation, EGF-Coa treatment recovered horizontal migration of epidermis over the newly deposited dermal matrix. EGF-Coa treatment also resulted in reduced levels of proinflammatory cytokines IL-1, IL-6, and THF-α. Freeze-dried coacervates packaged in aluminum pouches were stable for up to 4 months at 4 and 25 °C in terms of appearance, purity by RP-HPLC, and in vitro release profiles. There were significant physical and chemical changes in relative humidity above 33% or at 37 °C, suggesting the requirement for moisture-proof packaging and cold chain storage for long term stability. We propose low molecular weight gelatin type A and sodium alginate (LWGA-SA) coacervates as a novel EGF delivery system with enhanced efficacy for chronic wounds.

In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies.

Antibody immunotherapy is revolutionizing modern medicine. The field has advanced dramatically over the past 40 years, driven in part by major advances in isolation and manufacturing technologies that have brought these important biologics to the forefront of modern medicine. However, the global uptake of monoclonal antibody (mAb) biologics is impeded by biophysical and biochemical liabilities, production limitations, the need for cold-chain storage and transport, as well as high costs of manufacturing and distribution. Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. These approaches turn the body into a biological factory for antibody production, eliminating many of the steps involved in bioprocesses and providing several other significant advantages, and differ from traditional gene therapy (permanent delivery) approaches. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others.

Novel technology for storage and distribution of live vaccines and other biological medicines at ambient temperature.

A novel, thin-film platform that preserves live viruses, bacteria, antibodies, and enzymes without refrigeration for extended periods of time is described. Studies with recombinant adenovirus in an optimized formulation that supports recovery of live virus through 16 freeze-thaw cycles revealed that production of an amorphous solid with a glass transition above room temperature and nitrogen-hydrogen bonding between virus and film components are critical determinants of stability. Administration of live influenza virus in the optimized film by the sublingual and buccal routes induced antibody-mediated immune responses as good as or better than those achieved by intramuscular injection. This work introduces the possibility of improving global access to a variety of medicines by offering a technology capable of reducing costs of production, distribution, and supply chain maintenance.