Direct materials for restoring caries lesions: Systematic review and meta-analysis-a report of the American Dental Association Council on Scientific Affairs.

BACKGROUND: The goal of restoring caries lesions is to protect the pulp, prevent progression of the disease process, and restore the form and function of the tooth. The purpose of this systematic review was to determine the effect of different direct restorative materials for treating cavitated caries lesions on anterior and posterior primary and permanent teeth. TYPE OF STUDIES REVIEWED: The authors included parallel and split-mouth randomized controlled trials comparing the effectiveness of direct restorative materials commercially available in the United States placed in vital, nonendodontically treated primary and permanent teeth. Pairs of reviewers independently conducted study selection, data extraction, and assessments of risk of bias and certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The authors conducted pair-wise meta-analyses to summarize the evidence and calculated measures of association and their 95% CIs. RESULTS: Thirty-eight randomized controlled trials were eligible for analysis, which included data on Class I and Class II restorations on primary teeth and Class I, Class II, Class III, Class V, and root surface restorations on permanent teeth. Included studies assessed the effect of amalgam, resin composite, compomer, conventional glass ionomer cement, resin-modified glass isomer cement, and preformed metal crowns. Moderate to very low certainty evidence suggested varying levels of effectiveness across restorative materials. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Owing to a relatively low event rate across various outcomes indicating restoration failure, there was limited evidence to support important differences between direct restorative materials used in practice.

An Oral-mucosa-on-a-chip sensitively evaluates cell responses to dental monomers.

Knowledge of human gingival cell responses to dental monomers is critical for the development of new dental materials. Testing standards have been developed to provide guidelines to evaluate biological functionality of dental materials and devices. However, one shortcoming of the traditional testing platforms is that they do not recapitulate the multi-layered configuration of gingiva, and thus cannot evaluate the layer-specific cellular responses. An oral mucosa-chip with two cell layers was previously developed as an alternative platform to assess the oral mucosa responses to dental biomaterials. The mucosa-chip consists of an apical keratinocyte layer attached to a fibroblast-embedded collagen hydrogel through interconnecting pores in a three-microchannel network. Here, cell responses in the mucosa-chip were evaluated against 2-hydroxyethyl methacrylate (HEMA), a common monomer used in restorative and aesthetic dentistry. The response of mucosal cell viability was evaluated by exposing the chip to HEMA of concentrations ranging from 1.56 to 25 mM and compared to cells in conventional well-plate monoculture. The co-cultured cells were then stained and imaged with epifluorescence and confocal microscopy to determine the layer-specific responses to the treatment. Mucosa-chips were demonstrated to be more sensitive to assess HEMA-altered cell viability than well-plate cultures, especially at lower doses (1.56 and 6.25 mM). The findings suggest that the mucosa-chip is a promising alternative to traditional platforms or assays to test a variety of biomaterials by offering a multi-layered tissue geometry, accessible layer-specific information, and higher sensitivity in detecting cellular responses.

Use of Protein Repellents to Enhance the Antimicrobial Functionality of Quaternary Ammonium Containing Dental Materials.

An advancement in preventing secondary caries has been the incorporation of quaternary ammonium containing (QAC) compounds into a composite resin mixture. The permanent positive charge on the monomers allows for electrostatic-based killing of bacteria. Spontaneous adsorption of salivary proteins onto restorations dampens the antimicrobial capabilities of QAC compounds. Protein-repellent monomers can work with QAC restorations to achieve the technology's full potential. We discuss the theory behind macromolecular adsorption, direct and indirect characterization methods, and advances of protein repellent dental materials. The translation of protein adsorption to microbial colonization is covered, and the concerns and fallbacks of the state-of-the-art protein-resistant monomers are addressed. Last, we present new and exciting avenues for protein repellent monomer design that have yet to be explored in dental materials.

Physicochemical, Mechanical, and Antimicrobial Properties of Novel Dental Polymers Containing Quaternary Ammonium and Trimethoxysilyl Functionalities.

The aims of this study were to evaluate the physicochemical and mechanical properties, antimicrobial (AM) functionality, and cytotoxic potential of novel dental polymers containing quaternary ammonium and trimethoxysilyl functionalities (e.g., N-(2-(methacryloyloxy)ethyl)-N,N-dimethyl-3-(trimethoxysilyl)propan-1-aminium iodide (AMsil1) and N-(2-(methacryloyloxy)ethyl)-N,N-dimethyl-11-(trimethoxysilyl)undecan-1-aminium bromide (AMsil2)). AMsil1 or AMsil2 were incorporated into light-cured (camphorquinone + ethyl-4-N,N-dimethylamino benzoate) urethane dimethacrylate (UDMA)/polyethylene glycol-extended UDMA/ethyl 2-(hydroxymethyl)acrylate (EHMA) resins (hereafter, UPE resin) at 10 or 20 mass %. Cytotoxic potential was assessed by measuring viability and metabolic activity of immortalized mouse connective tissue and human gingival fibroblasts in direct contact with monomers. AMsil-UPE resins were evaluated for wettability by contact angle measurements and degree of vinyl conversion (DVC) by near infra-red spectroscopy analyses. Mechanical property evaluations entailed flexural strength (FS) and elastic modulus (E) testing of copolymer specimens. The AM properties were assessed using Streptococcus mutans (planktonic and biofilm forms) and Porphyromonas gingivalis biofilm. Neither AMsil exhibited significant toxicity in direct contact with cells at biologically relevant concentrations. Addition of AMsils made the UPE resin more hydrophilic. DVC values for the AMsil-UPE copolymers were 2%-31% lower than that attained in the UPE resin control. The mechanical properties (FS and E) of AMsil-UPE specimens were reduced (11%-57%) compared to the control. Compared to UPE resin, AMsil1-UPE and AMsil2-UPE (10% mass) copolymers reduced S. mutans biofilm 4.7- and 1.7-fold, respectively (p ≤ 0.005). Although not statistically different, P. gingivalis biofilm biomass on AMsil1-UPE and AM AMsil2-UPE copolymer disks were lower (71% and 85%, respectively) than that observed with a commercial AM dental material. In conclusion, the AM function of new monomers is not inundated by their toxicity towards cells. Despite the reduction in mechanical properties of the AMsil-UPE copolymers, AMsil2 is a good candidate for incorporation into multifunctional composites due to the favorable overall hydrophilicity of the resins and the satisfactory DVC values attained upon light polymerization of AMsil-containing UDMA/PEG-U/EHMA copolymers.

Oral mucosa-on-a-chip to assess layer-specific responses to bacteria and dental materials.

The human oral mucosa hosts a diverse microbiome and is exposed to potentially toxic biomaterials from dental restoratives. Mucosal health is partly determined by cell and tissue responses to challenges such as dental materials and pathogenic bacteria. An in vitro model to rapidly determine potential layer-specific responses would lead to a better understanding of mucosal homeostasis and pathology. Therefore, this study aimed to develop a co-cultured microfluidic mucosal model on-a-chip to rapidly assess mucosal remodeling and the responses of epithelial and subepithelial layers to challenges typically found in the oral environment. A gingival fibroblast-laden collagen hydrogel was assembled in the central channel of a three-channel microfluidic chamber with interconnecting pores, followed by a keratinocyte layer attached to the collagen exposed in the pores. This configuration produced apical and subepithelial side channels capable of sustaining flow. Keratinocyte, fibroblast, and collagen densities were optimized to create a co-culture tissue-like construct stable over one week. Cells were stained and imaged with epifluorescence microscopy to confirm layer characteristics. As proof-of-concept, the mucosal construct was exposed separately to a dental monomer, 2-hydroxylethyl methacrylate (HEMA), and the oral bacteria Streptococcus mutans. Exposure to HEMA lowered mucosal cell viability, while exposure to the bacteria lowered trans-epithelial electrical resistance. These findings suggest that the oral mucosa-on-a-chip is useful for studying oral mucosal interactions with bacteria and biomaterials with a histology-like view of the tissue layers.

Antimicrobial Monomers for Polymeric Dental Restoratives: Cytotoxicity and Physicochemical Properties.

A trend for the next generation of polymeric dental restoratives is to incorporate multifunctional capabilities to regulate microbial growth and remineralize tooth surfaces. Polymerizable 2-(methacryloyloxy)-N-(2-(methacryloyloxy)ethyl)-N,N-dimethylethan-1-aminium bromide (IDMA1) and N,N'-([1,1'-biphenyl]-2,2'-diylbis(methylene))bis(2-(methacryloyloxy)-N,N-dimethylethan-1-aminium) bromide (IDMA2), intended for utilization in bi-functional antimicrobial and remineralizing composites, were synthesized, purified with an ethanol-diethyl ether-hexane solvent system, and validated by nuclear magnetic resonance (¹H and 13C NMR) spectroscopy, mass spectrometry, and Fourier-transform infrared spectroscopy. When incorporated into light-curable urethane dimethacrylate (UDMA)/polyethylene glycol-extended UDMA (PEG-U)/ethyl 2-(hydroxymethyl)acrylate (EHMA) (assigned UPE) resins, IDMAs did not affect the overall resins' hydrophilicity/hydrophobicity balance (water contact angle: 60.8-65.5°). The attained degrees of vinyl conversion (DVC) were consistently higher in both IDMA-containing copolymers and their amorphous calcium phosphate (ACP) composites (up to 5% and 20%, respectively) reaching 92.5% in IDMA2 formulations. Notably, these high DVCs values were attained without an excessive increase in polymerization stress. The observed reduction in biaxial flexure strength of UPE-IDMA ACP composites should not prevent further evaluation of these materials as multifunctional Class V restoratives. In direct contact with human gingival fibroblasts, at biologically relevant concentrations, IDMAs did not adversely affect cell viability or their metabolic activity. Ion release from the composites was indicative of their strong remineralization potential. The above, early-phase biocompatibility and physicochemical tests justify further evaluation of these experimental materials to identify formulation(s) suitable for clinical testing. Successful completion is expected to yield a new class of restoratives with well-controlled bio-function, which will physicochemically, mechanically, and biologically outperform the conventional Class V restoratives.

Utility of Amorphous Calcium Phosphate-Based Scaffolds in Dental/Biomedical Applications.

Calcium phosphate (CaP) materials are important inorganic constituents in biological hard tissue. CaPs, including amorphous calcium phosphate (ACP) have been widely applied in dental and biomedical applications, such as tissue engineering. Scaffold constructs are commonly used as templates to create a biomimetic environment. This review considers ACP scaffold fabrication techniques, including tissue-engineered constructs with intrinsic incorporation of ACP as well as scaffolds formed via precipitation of mineralized solutions on a substrate. Attention is given to the approaches used to assess cellular and molecular responses elicited by ACP scaffolds, such as biocompatibility, cell conductivity, cell adhesion, cell differentiation, phenotypic profiles, and gene expression. Bioactivity of composite ACP scaffolds can be enhanced by incorporating biomolecules to create multi-functional properties. Herein we summarize the use of antibiotics, growth factors, and gene delivery systems to create multi-functional ACP scaffolds. Inasmuch as CaP materials have been investigated as drug delivery systems for many years, we briefly consider the potential of integrating these systems with existing ACP scaffold constructs and the potential for precision medicine.

Bioactive Polymeric Materials for Tissue Repair.

Bioactive polymeric materials based on calcium phosphates have tremendous appeal for hard tissue repair because of their well-documented biocompatibility. Amorphous calcium phosphate (ACP)-based ones additionally protect against unwanted demineralization and actively support regeneration of hard tissue minerals. Our group has been investigating the structure/composition/property relationships of ACP polymeric composites for the last two decades. Here, we present ACP's dispersion in a polymer matrix and the fine-tuning of the resin affects the physicochemical, mechanical, and biological properties of ACP polymeric composites. These studies illustrate how the filler/resin interface and monomer/polymer molecular structure affect the material's critical properties, such as ion release and mechanical strength. We also present evidence of the remineralization efficacy of ACP composites when exposed to accelerated acidic challenges representative of oral environment conditions. The utility of ACP has recently been extended to include airbrushing as a platform technology for fabrication of nanofiber scaffolds. These studies, focused on assessing the feasibility of incorporating ACP into various polymer fibers, also included the release kinetics of bioactive calcium and phosphate ions from nanofibers and evaluate the biorelevance of the polymeric ACP fiber networks. We also discuss the potential for future integration of the existing ACP scaffolds into therapeutic delivery systems used in the precision medicine field.

Blow-spun chitosan/PEG/PLGA nanofibers as a novel tissue engineering scaffold with antibacterial properties.

Blow spinning is continuing to gain attention in tissue engineering, as the resultant nanofibrous structures can be used to create a biomimetic environment. In this study, blow spinning was used to construct nanofiber scaffolds with up to 10 % chitosan and poly(DL-lactide-co-glycolide) in the absence or presence of poly(ethylene glycol). Scanning electron microscopy demonstrated that nanofibers were distributed randomly to form three-dimensional mats. With respect to chitosan concentration, the average fiber diameter did not differ statistically in either the absence or presence of poly(ethylene glycol). In poly(ethylene glycol)-formulations, the average fiber diameter ranged from (981.9 ± 611.3) nm to (1139.2 ± 814.2) nm. In vitro cellular metabolic activity and proliferation studies using keratinized rat squamous epithelial cells (RL-65) showed that cytocompatibility was not compromised with the addition of poly(ethylene glycol). The cell responses at lower (1 and 2.5 %) chitosan concentrations were not significantly different from the groups without chitosan or no scaffold when cultivated for 3, 6, or 9 days. However, >15 % reduction in cellular responses were observed at 10 % chitosan. In presence of poly(ethylene glycol), nearly a 1-log incremental reduction in the number of colony forming units of Streptococcus mutans occurred as the chitosan concentration increased from 0-1 to 2.5 %. Bacterial preparations tested with poly(ethylene glycol) and 5 or 10 % chitosan were not significantly different than the positive kill control. Taken together, the most favorable conditions for attaining cytocompatibility and maintaining antibacterial functionality existed in poly(ethylene glycol)/poly(DL-lactide-co-glycolide) blow-spun scaffolds with integrated 1 or 2.5 % chitosan.

Risk assessment and sensitivity meta-analysis of alveolar osteitis occurrence in oral contraceptive users.

BACKGROUND: In this study, the authors conducted an alveolar osteitis (AO) risk assessment and global sensitivity meta-analysis within populations using oral contraceptives (OCs). Sex, smoking, and timing within the menstrual cycle were considered as factors. TYPES OF STUDIES REVIEWED: Eligibility criteria for inclusion of a study in the meta-analysis were experimental or medical record survey data evaluating AO and OC use, ability to draw pairwise comparisons for factors of interest, and description of the number of AO events relative to the number of participants in the respective group. RESULTS: The risk ratio of AO in females not using OCs was 1.2 greater (P ≤ .05) than that in males. Among females, OC use significantly increased (P ≤ .05) the average risk of AO occurrence by nearly 2-fold (13.9% versus 7.5%). There was no statistical evidence of lower risk in females menstruating at the time of exodontia. In 85.7% of the studies, smokers had an overall higher rate (P ≤ .05) of AO than did nonsmokers. CONCLUSIONS AND PRACTICAL IMPLICATIONS: To mitigate the increased risk of AO occurrence in females, the dentist should be cognizant of patients using OCs and smoking tobacco.

Diagnostic accuracy of a point-of-care blood typing kit conducted by potential end users.

The usability of a rapid point-of-care ABO-Rh blood typing kit was determined by comparing the performance of individuals with extensive medical training/experience to those with a lesser extent. Subjects were asked to use the blood typing kit with their own blood. These outcomes were compared to that listed in the subject's medical record, stamped on their dog tag, and the result interpreted by a laboratorian. For all participants, there was ∼80% consistency between the result interpreted by the subject and that stated in their medical record. The participant's level of formal education (P ≤ 0.05) affected the accuracy of the blood typing kit. When comparing the subject's outcome to that stated in their medical record, the performance of individuals in the Medical Corps was approximately 10% and 25% higher (P < 0.05) than that observed with Hospital Corpsman or Medical Service Corps members, respectively. To remove bias that can occur when interpreting the blood type of oneself, the subjects also interpreted the result from cards prepared by the investigator. Taken together, a discrepancy between the potential diagnostic accuracy of the kit and that observed with potential end users was identified.

Antimicrobial activity of nanoemulsion in combination with cetylpyridinium chloride in multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii has emerged as a serious problematic pathogen due to the ever-increasing presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria, enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion preparations against four Acinetobacter baumannii isolates to identify the most suitable preparation for further evaluation. Among them, N5, which contains 10% (vol/vol) Triton X-100, 25% (vol/vol) soybean oil, and 1% (wt/vol) cetylpyridinium chloride (CPC), showed the best efficacy against A. baumannii in both its planktonic and biofilm forms and was selected for further study. Our data demonstrate that, while the killing of planktonic forms of A. baumannii was due to the 1% CPC component of our nanoemulsions, the breakdown of biofilms was achieved via the emulsified oil and detergent fractions. Furthermore, we documented the effect of ethanol and NaCl in combination with N5 on planktonic A. baumannii. In killing curves of N5 combined with other agents (ethanol or NaCl), a synergistic effect of a ≥ 2-log decrease in CFU/ml was observed. The antibiofilm activity of N5 was confirmed via a cell proliferation test and scanning electron microscopy. The effects of exposure to severe environmental conditions, which simulates the field conditions in Iraq and Afghanistan, were evaluated, and this exposure did not affect the overall antimicrobial activity of N5. These studies lay a solid foundation for the utilization of nanoemulsions against the antibiotic-resistant forms of A. baumannii.

The effect of simulated field storage conditions on the accuracy of rapid user-friendly blood pathogen detection kits.

Being able to test for the presence of blood pathogens at forward locations could reduce morbidity and mortality in the field. Rapid, user-friendly blood typing kits for detecting Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and Hepatitis B Virus (HBV) were evaluated to determine their accuracy after storage at various temperatures/humidities. Rates of positive tests of control groups, experimental groups, and industry standards were compared (Fisher's exact chi2, p < or = 0.05). Compared to the control group, 2 of 10 HIV detection devices were adversely affected by exposure to high temperature/high humidity or high temperature/low humidity. With one exception, none of the environmentally exposed HCV or HBV detection devices exhibited significant differences compared to those stored under control conditions. For HIV, HCV, and HBV devices, there were differences compared to the industry standard. Collectively, this evaluation of pathogen detection kits revealed that diagnostic performance varies among products and storage conditions, and that the tested products cannot be considered to be approved for use to screen blood, plasma, cell, or tissue donors.

Accuracy of user-friendly blood typing kits tested under simulated military field conditions.

Rapid user-friendly ABO-Rh blood typing kits (Eldon Home Kit 2511, ABO-Rh Combination Blood Typing Experiment Kit) were evaluated to determine their accuracy when used under simulated military field conditions and after long-term storage at various temperatures and humidities. Rates of positive tests between control groups, experimental groups, and industry standards were measured and analyzed using the Fisher's exact chi-square method to identify significant differences (p < or = 0.05). When Eldon Home Kits 2511 were used in various operational conditions, the results were comparable to those obtained with the control group and with the industry standard. The performance of the ABO-Rh Combination Blood Typing Experiment Kit was adversely affected by prolonged storage in temperatures above 37 degrees C. The diagnostic performance of commercial blood typing kits varies according to product and environmental storage conditions.

Stability of user-friendly blood typing kits stored under typical military field conditions.

To help preserve in-theater strength within deployed military units, commercially available, rapid, user-friendly ABO-Rh blood typing kits were evaluated to determine their stability in storage conditions commonly encountered by the warfighter. Methods for environmental exposure testing were based on MIL-STD-810F. When Eldon Home Kits 2511 were exposed to various temperature/relative humidity conditions, the results were comparable to those obtained with the control group and those obtained with industry-standard methods. For the ABO-Rh Combination Blood Typing Experiment Kits, 2 of the exposure treatments rendered them unusable. In addition, a third set of exposure treatments adversely affected the kits, resulting in approximately 30% blood type misclassifications. Collectively, this evaluation of commercial blood typing kits revealed that diagnostic performance can vary between products, lots, and environmental storage conditions.

The anthrax vaccine: no new tricks for an old dog.

The original license for production of the anthrax vaccine, Anthrax Vaccine Adsorbed (AVA), was issued in 1970. Since that time, over 8 million AVA immunizations have been administered to 2+ million individuals. In 2002, the National Academy of Sciences, Institute of Medicine, reviewed the safety and efficacy of AVA. They concluded that the vaccine is acceptably safe and effective in protecting humans against anthrax. The vaccine should protect people against all known strains of anthrax bacteria, as well as against any strains that might be created by potential terrorists or others. Although the Institute of Medicine concluded that AVA was reasonably safe, they noted that it is fairly common for people to experience local reactions (e.g., redness and swelling at the injection site) and for a smaller number to experience systemic reactions such as fever and malaise, within hours or days of vaccination. Results of animal studies done previously and subsequent to this report are generally in agreement. For instance, AVA vaccination increases the level of anthrax anti-protective antigen IgG (anti-PA IgG), which is thought to be one possible correlate of protection (although absolute protective concentrations have not been identified in humans). Anthrax lethal factor neutralization has also been identified as possibly being an important additional correlate of immunity. Future vaccine research efforts include developing a recombinant anthrax vaccine and anthrax monoclonal antibodies to block the anthrax toxin(s). It is projected that the next-generation vaccine will elicit a markedly increased anti-anthrax immune response within a shorter time period and consequently, will enable the easier inoculations of individuals working within high-risk areas.

Rapid point-of-care test to detect broad ranges of protective antigen-specific immunoglobulin G concentrations in recipients of the U.S.-licensed anthrax vaccine.

Currently, there is no routine monitoring of an immune response to the anthrax vaccine. Simple on-site tests are needed to evaluate the antibody response of anthrax-vaccinated individuals in the Armed Forces and others at high risk. Using a prototype lateral flow assay (LFA) (R. E. Biagini, D. L. Sammons, J. P. Smith, B. A. MacKenzie, C. A. F. Striley, J. E. Snawder, S. A. Robertson, and C. P. Quinn, Clin. Vaccine Immunol. 13:541-546, 2006), we investigated the agreement between a validated anthrax protective antigen (PA) immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and the LFA for 335 unvaccinated and vaccinated subjects. We also investigated the performance of the LFA under the following conditions: thermal shock (i.e., thermal cycling between temperature extremes), high temperature/high relative humidity, high temperature/low relative humidity, and low temperature/low relative humidity. With the anti-PA ELISA used as a standard, the LFA was shown to be optimally diagnostic at 11 microg/ml anti-PA-specific IgG. At this concentration, the LFA specificity and sensitivity were 98% (95% confidence interval [CI], 97% to 100%) and 92% (CI, 88% to 97%), respectively. Receiver operating characteristic curve analysis yielded an area under the curve value of 0.988 (CI, 0.976 to 1.00), suggesting that the LFA is an extremely accurate diagnostic test. For < or = 4 or > or = 50 microg/ml PA-specific IgG, the LFA results for each environmental condition were identical to those obtained in the laboratory. These data indicate that this rapid point-of-care test would be a feasible tool in monitoring the serological antibody responses of individuals that have been vaccinated against anthrax.

Detection of anti-protective antigen salivary IgG antibodies in recipients of the US licensed anthrax vaccine.

The immune response of anthrax vaccine recipients is not routinely monitored. For field use, a noninvasive test would be beneficial to evaluate the antibody response of anthrax-vaccinated individuals working within a high-risk area of possible exposure. The aim of this cross-sectional study was to determine whether whole saliva can be used as a surrogate matrix for the detection of 83 kDa protective antigen (PA)-specific immunoglobulin G (IgG). An enzyme-linked immunosorbent assay was used for the detection of PA-specific IgG in matched samples (serum and saliva) that were collected from vaccinated and unvaccinated participants. Specimens from 180 individuals revealed a positive correlation (r=0.73; P<0.0001) between the level of PA-specific antibody detected in the saliva and serum. The number of vaccinations influenced both the saliva and serum antibody response. On average, the concentration of serological PA-specific antibodies in the vaccinated group was nearly 1600-fold greater than that in saliva. The magnitude of the salivary anti-PA antibody response was not significantly affected by the consumption of food, beverage, or tobacco products or other factors, which could potentially affect oral fluid properties. These results suggest that an oral fluid-based immunoassay may be a feasible alternative to monitoring the serological antibody response of individuals that have been vaccinated against anthrax.

The impact of incomplete vaccination schedules on the magnitude and duration of protective antigen-specific IgG responses in recipients of the US licensed anthrax vaccine.

Using a cross-sectional analysis design, we measured serum anti-protective antigen (PA) concentrations in individuals receiving six or fewer US licensed anthrax vaccinations. Samples were collected from 363 individuals with a mean of 29.6+/-8.42 months after their last vaccination (range 3-57 months). An enzyme-linked immunosorbent assay (ELISA) developed and validated by the Centers for Disease Control and Prevention (CDC) was used to evaluate the range and status of anthrax vaccine-induced serum antibody concentrations. A significant correlation (r=0.73, P< or =0.001) was found to exist between the number of vaccinations received and specific anti-PA immunoglobulin G (IgG) concentrations. We observed two discrete groups comprised of one to three doses (5.9-11.7 microg/ml) and four to six doses (26.2-30.2 microg/ml). These data indicate that anti-PA IgG is present at low but detectable levels after as few as two vaccinations (5.9+/-6.43 microg/ml). These findings may have significance for anthrax vaccine recipients who are unable to complete the primary or full regimen with this licensed product.