A ‘data point’ was defined as a pre- or post-introduction prevalence in a single year, age group, and population. A ‘data set’ was

defined as two data points, separated in time, from the same age group and population, typically one pre- and one post- introduction. Where possible, the ‘pre’ period was before PCV licensing in the country, excluding the year licensed unless that year’s pre-data were drawn only from months prior to introduction (Appendix B.1); the ‘post’ period began no earlier than the year following introduction. GSK126 ic50 Year of introduction was based on a compilation of data from WHO [19] and VIMS [20] databases which identified the year in which PCV was widely adopted on a national or relevant regional scale. In the few cases with significant lag time between national licensure and wide adoption, the breakpoint identified by the author was used (low-coverage vs. high-coverage, or pre-licensure vs. post-licensure.) Percentage change in outcome measures was calculated by comparing the most recent pre-introduction data available to each available post-introduction time point. For data presented as incidence rates and case counts, percentage change was calculated as

(pre-introduction – post-introduction)/pre-introduction × 100%, where negative Selleckchem MK 2206 values for percentage change denote an increase. If the study outcome was the proportion VT of all IPD cases, percentage change was transformed into a comparable measure based on incidence rates and case counts as follows: Percentage change = [1 − ((%VT IPD post) × (%NVT IPD pre))/(%VT IPD pre) × (%NVT IPD post)] × 100%. Data were stratified by elapsed years since introduction to assess trends with time, and by age group (<5, 5 to <18, 18 to <50, 50 to <65, ≥65 years) to assess differential effects across age categories. Points not fitting within a single age stratum with minimal overlap

were classified based on the oldest stratum included. Where a data point represented multiple post-introduction Amisulpride years (i.e., “2001–2003”), the midpoint was used to calculate the number of years since PCV introduction. Where possible, data were also stratified into populations receiving booster doses and those without, and indigenous versus general populations. Effects of different primary dose schedules are addressed elsewhere [21], [22], [23] and [24]. When both IPD and carriage were available, we compared their percentage changes to assess their relationship. When both VT-IPD and PCV coverage levels in the community over time were available, we evaluated the relationship between PCV uptake and VT-IPD impact. Countries that implemented a catch-up schedule in those <2 or <5 years were identified; since catch-up coverage is generally less than complete, we did not further distinguish the magnitude of indirect effects by use of catch-up but considered these mixed populations.

In contrast, although they do not represent a correlate of protection, serum antibody levels following LAIV can be more consistently evaluated as the serum compartment is not subject to the same variability in content and sampling. For this reason, serum antibody responses following LAIV are the preferred method for evaluating the immunologic comparability of vaccine formulations signaling pathway or administration

schemes [13], [21], [45], [46], [47], [48] and [49]. In the current analysis, IgA and HAI responses were correlated, as IgA responses were more frequently observed among subjects with a HAI response. The primary limitation of the current analysis is the small size of the study cohorts. Although the pooled sample enabled an examination of the relationship between IgA and the incidence of influenza illness, the analysis would have benefited from larger cohort populations.

Averaging of IgA ratios across studies can also be problematic due to variability in values across types/subtypes and across studies. However, it is reassuring that the conclusions of the pooled analyses were supported by similar and consistent trends by study and type/subtype. In the analysis of the relationship between IgA and culture-confirmed influenza illness, it is possible that subjects without culture-confirmed influenza illness still experienced influenza infection; however, identification of these cases would likely have strengthened the Luminespib supplier observed relationship. Additionally, the assay was specific to IgA and did not evaluate nasal IgM or IgG antibody, which can also contribute to mucosal immunity [1]; a postvaccination increase in nasal enough wash IgG was observed in a prior study of LAIV [36]. In study 3, significant increases in total IgA were observed between baseline and postvaccination samples. Among prevaccination samples, which would not be subject to vaccine-induced effects, subjects who enrolled later had significantly higher total IgA, suggesting that

site sample collection technique improved over time. This observation supports the practice of providing interspecimen standardization by reporting IgA values as ratios of specific to total IgA. A postvaccination rise in total IgA has also been reported following intranasal measles vaccination; however, the study lacked a placebo control and thus it was not possible to determine whether the total IgA increase was vaccine-attributable [50]. In conclusion, results from 3 clinical studies in young children demonstrated that LAIV induced measurable strain-specific IgA after vaccination and that IgA responses are associated with protection from subsequent influenza illness. However, the inherent heterogeneity in nasal antibody levels and variability in nasal specimen collection hinders the precise evaluation of mucosal antibody responses, and measured IgA responses do not fully explain LAIV-induced protection. This study was sponsored by MedImmune, LLC.

In contrast, the drug permeability in the BA direction was decreased in presence of PSC833 in all cell layers (Table 2). In addition to its inhibitory properties on various MRP carriers [32], MK571 has been recently reported to interfere with the activity of OATP1B3 and OATP2B1 at a concentration as low as 1 μM [42] and [43]. Its modulatory effects on other OATP transporters present in Calu-3 layers (Table 1) are currently unknown. Nevertheless, the compound has been shown not to interact with MDR1 [33], which we confirmed in an IUC2 shift

assay. Although PSC833 was originally developed as a specific MDR1 inhibitor, it has since been reported to inhibit other PD0332991 concentration ABC transporters, such as the bile salt extrusion pump (BSEP) [44], MRP2 [45] or the breast cancer resistance protein (BCRP, Solvo Biotech

website) and its ability to inhibit OATP transporters has been suggested [46]. Taken together, 3H-digoxin permeability data in Calu-3 layers do not support an exclusive participation of the MDR1 transporter in its apparent efflux and suggest the involvement of one or several ATP-independent transport system(s). Similarly, it has previously been demonstrated that MDR1 was not the sole transporter responsible for digoxin asymmetric transport in Autophagy high throughput screening the Caco-2 intestinal absorption model [33] and in MDR1 transfected MDCK cell layers [47]. Although this/these transporter(s) remain(s) to be identified, OATP4C1 might be a possible candidate since

digoxin is a known substrate [20] and [21], the transporter is present in Calu-3 layers and a lower gene expression Casein kinase 1 was observed at a high passage number (Table 1). Assuming protein levels are in agreement with those of mRNA transcripts, this could explain the reduced digoxin apparent efflux in high passage cell layers. This assumption implies a basolateral location of OATP4C1 in Calu-3 layers in line with the basolateral presence of OATP transporters that has been recently postulated in the airway epithelium of foals [48]. However, there remains a possibility that digoxin is transported across bronchial epithelial cell layers by a transporter yet to be characterised, as suggested in other cell culture models [22], [23] and [47]. For instance, in addition to the apical MDR1 efflux pump, a basolaterally located uptake transporter was required to account for digoxin net secretory transport in MDCKII-MDR1 cell layers but this transporter could not be identified using a panel of inhibitors [47]. As previously debated for the MDCKII-MDR1 absorption model [47], the likely involvement of multiple transporters in digoxin bidirectional transport in Calu-3 layers questions its suitability for probing MDR1 activity in the bronchial epithelium.

Therefore, the development of a vaccine to prevent Trichinella infection in domestic CX-5461 molecular weight animals and humans is a necessary approach for controlling this disease. Heat shock proteins (Hsps) are a group of proteins that are induced upon exposure to a range of environmental stresses that include heat shock, oxygen deprivation, pH extremes, and nutrient deprivation

[6]. This family of proteins is highly conserved among different species and highly immunogenic during infections [7], [8], [9] and [10]. The heat shock proteins have recently been reported to play significant roles in antigen presentation, the activation of lymphocytes, and the maturation of dendritic cells [11]. Several researchers have also reported on the protective efficacies of Hsps against various infections by Plasmodium yoelii [7], Brugia malayi [8], Leishmania donovani [9], and Hantaan virus [12]. Several www.selleckchem.com/products/AZD6244.html heat-shock proteins, such as Hsp60, Hsp70 and Hsp80, have been reported and named according to their molecular weight. Of these proteins, Hsp70 is the

most conserved among different organisms, and Hsp70 is an immunodominant antigen during infections caused by a number of pathogens [6], [13] and [14]. In our previous study, Hsp70 from Trichinella spiralis (Ts-Hsp) was cloned via the immunoscreening of a T. spiralis cDNA library with immune serum, and the recombinant Ts-Hsp70 protein (rTs-Hsp70) was expressed in an Escherichia coli expression system [15]. The rTs-Hsp70 protein was recognized not only by the sera from patients with trichinellosis but also in the sera from T. spiralis-infected rabbits, pigs, and mice. The native Ts-Hsp70 was found in the crude somatic extracts of T. spiralis muscle larvae and adult worms. Vaccination with rTs-Hsp70 induces a strong immune response and a 37% reduction in muscle

larvae upon T. spiralis larval challenge compared to PBS control groups [15]. Further investigations in our lab demonstrated that the immunization of mice with rTs-Hsp70 elicited a systemic Th1/Th2 immune response (data not shown). However, as a possible vaccine candidate antigen, the mechanism of Ts-Hsp70-mediated protection Dipeptidyl peptidase requires further clarification. One mechanisms by which an antigen is presented to the immune system is based on the antigen’s ability to alter the maturation of dendritic cells (DCs). DCs are the typical antigen presenting cells (APCs) that induce primary immune responses through the activation and differentiation of helper T cells [16] and [17] and play a crucial role in helminth infections [18] and [19]. Currently, it remains unclear whether the protective immune response against T. spiralis infection induced by rTs-Hsp70 is related to DC activation. In this study, the interaction between rTs-Hsp70 and DCs derived from mouse bone marrow was investigated.

2 and Table 4. Pain at the injection site was the most frequently reported solicited local AE. Following the first dose, it was reported by 72.7–83.8% of children in adjuvanted vaccine groups and by 44.5% of children in Metformin cost the non-adjuvanted vaccine group. Following booster vaccination, pain was again the most frequently reported solicited local symptom, reported for 61.5–79.4% of children who received the

adjuvanted vaccines and for 44.5% of children who received the non-adjuvanted vaccine. Overall, grade 3 solicited local AEs were reported for ≤3.0% of subjects following primary vaccination and ≤5.9% of subjects following booster vaccination. Following the first vaccine dose, fatigue (adjuvanted vaccines: 25.8–36.4% of children; non-adjuvanted vaccine: 26.4% of children), headache (adjuvanted vaccines: 25.8–39.7% of children; non-adjuvanted: 33.6% of children) and myalgia (adjuvanted vaccines: 24.2–32.4% of children; non-adjuvanted: 16.4% of children) were the most frequently reported solicited general AEs. The reporting of these AEs following the second vaccine dose was lowest for the non-adjuvanted vaccine (18.2%, 15.5% and 7.3% of children, respectively), and highest for the second dose of AS03B-adjuvanted 1.9 μg learn more HA vaccine (23.5%, 39.7% and 26.5% of children, respectively). Following booster vaccination, fatigue (adjuvanted vaccines:

30.8–44.6% of children; non-adjuvanted vaccine: 17.3% of children), headache (adjuvanted vaccines: 35.4–47.1% of children; non-adjuvanted: 22.7% of children) and myalgia (adjuvanted vaccines: 24.6–29.2% of children; non-adjuvanted: 18.2% of children) were the most frequently reported solicited general AE. Grade 3 solicited general AEs were reported by ≤1.5% of children after the primary and booster vaccinations. Overall, 42.4–64.7% and 30.0–55.9% of solicited general AEs reported following primary and booster vaccination were considered by the investigators to be causally related to vaccination. At least one unsolicited AE was reported for 19.7–35.5% of children following primary vaccination and 4.4–10.8% of

children following booster vaccination (42-day follow-ups). At least one MAE was reported for 30.3–32.4% of children during the entire study period. Overall, at least one SAE was reported for 1.5–4.5% of children (10 SAEs in 10 subjects); Rolziracetam none were assessed as vaccination related. No pIMDs were identified. No concerning patterns in the clinical laboratory parameters were identified. ILI was reported for 12 children (2 in the AS03A-adjuvanted 3.75 μg HA vaccine group, 1 in the group receiving 1 priming dose of AS03B-adjuvanted 1.9 μg HA vaccine, 5 in the group receiving 2 priming doses of AS03B-adjuvanted 1.9 μg HA vaccine and 4 in non-adjuvanted 15 μg HA vaccine group). None were RT-qPCR positive for H1N1/2009 infection. The primary objective of the study was met.

Y1R may not be necessary for the cued-expression of fear, as intra-amygdalar administration of NPY robustly decreases the expression of conditioned fear,

but these effects are not replicated by Y1R agonists and are not blocked by pretreatment with a Y1R antagonist (Fendt et al., 2009). In this particular study, Y1R knockout mice showed slight elevations in freezing behavior during fear conditioning, but did not show an enhanced phenotype upon testing for the cued-expression of fear compared to wildtype mice (Fendt et al., 2009). In addition, NPY was still capable of reducing the cued-expression of fear in these Y1R deficient mice, suggesting that the Y1R may not be involved in this phase (Fendt et al., 2009). NPY can suppress the long-term incubation of conditioned fear, while delivery of NPY prior to extinction training attenuates AZD8055 freezing and enhances retention of extinguished fear memories (Gutman and et al, 2008, Lach and de Lima, 2013 and Pickens and et al, 2009). Y1R antagonism blocks NPY-induced reductions in freezing and blockade of amygdalar Y1R leads to deficient extinction retention (Gutman and et al, 2008 and Lach and de Lima, 2013). Consistent with pharmacological studies, NPY knockout mice display accelerated acquisition of conditioned fear, excessive recall of fear, and impaired fear extinction (Verma et al.,

2012). Interestingly, deletion of the Y1R has moderately similar effects, whereas knockout selleck inhibitor of the Y2R has no effect on fear (Verma et al., 2012). However, double Y1R and Y2R knockout mice exhibit a remarkably similar phenotype to NPY deficient mice, indicating that both receptor subtypes do play a role in aspects of fear conditioning (Verma et al., 2012). In an inescapable footshock paradigm, interactions between the NPY and CRF systems were evident as increased amygdalar CRFR1 and decreased Y1R mRNA were found concurrently in animals

displaying enhanced freezing time, and all of these effects were reversed in parallel following re-exposure to the footshock-paired environment (Hendriksen et al., 2012). Indirect evidence for NPY interactions with norepinephrine was obtained using auditory fear conditioning, in which centrally administered NPY and a Y1R agonist blunted fear-induced tachycardia (Tovote et al., 2004). These effects were blocked by a Y1R antagonist (Tovote et al., too 2004). NPY is implicated in depression-like behavior and produces antidepressant effects. For example, central administration of NPY dose-dependently reduces immobility and increases swimming time in the forced swim test (Redrobe and et al, 2005, Stogner and Holmes, 2000 and Redrobe and et al, 2002), a screening paradigm for pharmacological anti-depressant activity. Y1R agonists and Y2R antagonists also produce anti-depressant effects in forced swim (Redrobe et al., 2002), whereas Y1R antagonists block the anti-depressant effects of NPY (Redrobe et al., 2002).

Briefly, nitrocellulose bottom 96-well plates (MILLIPORE) were coated overnight at 4 °C with anti-IFN-γ monoclonal antibody (clone R4-6A2; Apoptosis inhibitor BD Biosciences) diluted in PBS. Plates were washed and blocked for 2 h with DMEM supplemented with 10% FCS. Spleen

cells of immunized mice were prepared in DMEM supplemented with 10% FCS and recombinant IL-2 (100 U/ml). Splenocytes were seeded at a density of 5 × 105 cells/well and stimulated with F3 antigenic fraction (5 μg/ml) during 20 h at 37 °C, 5% CO2. Plates were washed and incubated for 4 h, at room temperature, with a biotin-conjugate anti-mouse IFN-γ monoclonal antibody (clone XMG1.2; BD Biosciences) and, after the next wash step, with peroxidase-labeled streptavidin, for 2 h at room temperature. Reactions were detected with a peroxidase substrate containing 3,3′-diaminobenzidine Smad inhibitor tetrahydrochloride (1 mg/ml) and 30% hydrogen peroxide solution (1 μl/ml) in 50 mM Tris–HCL buffer, pH = 7.5. Reactions were stopped under running water, and spots were counted on a S5 Core ELISPOT Analyser (CTL). Four weeks after the boost immunization, mice were infected orally with 20 cysts of P-Br strain of T. gondii, obtained from macerated brains of infected Swiss-Webster reservoirs suspended in PBS. Animals were sacrificed 8 weeks after the challenge. The brains were collected, macerated and suspended in 1 ml of PBS. Cysts were counted, in

duplicates, under light microscope, in 10 μl of brain suspensions. All results were evaluated for their statistic significance by Student’s t-test (parametric data) or by Mann–Whitney test (non-parametric data) performed with Minitab version 14. Normal distribution of samples was assessed by Anderson Darling software. The recombinant NA38-SAG2 segment was developed to carry the SAG2 sequence of T. gondii flanked by the duplicated 3′ promoter and the extended native 5′ terminal sequence of 70 nucleotides corresponding to 28 nt of the 5′ promoter and a duplication

of the below last 42 nt of the NA coding sequence, located upstream the promoter ( Fig. 1). Recombinant Influenza A viruses harboring the dicistronic NA38-SAG2 segment (FLU-SAG2) were generated using the 12 plasmid-driven reverse genetics, as previously described [41]. Recombinant FLU-SAG2 viruses displayed a slightly altered phenotype ( Fig. 2A), but showed infectious titers (9.2 ± 3.2 × 107 pfu/ml) similar to wild type vNA (1.4 × 108 pfu/ml). The presence of SAG2 in recombinant NA segments was assessed in three FLU-SAG2 clones by RT-PCR with primers that allowed the amplification of the entire region of insertion of SAG2. As shown in Fig. 2B, amplification products of the expected size (∼900 bp) were observed for all clones analyzed. Moreover, these amplicons were sequenced and showed no mutation in SAG2 sequence as well as in the internal 3′promoter (data not shown). Taking together, these results showed that FLU-SAG2 viruses are genetically stable in cell culture.

VP7(T13) is an immuno-dominant orbivirus-species/serogroup-specific antigen [51], [60] and [61]. Antibodies to VP7 can neutralise the infectivity of BTV core-particles, but do not significantly neutralise intact virus particles [62]. The incorporation of baculovirus-expressed VP7 in previously reported vaccination studies using VP2 and VP5, also failed to enhance NAb

responses in sheep [43]. However, vaccination with BTV-VP7 has been shown to induce a partially-protective Selleck SB203580 cytotoxic T-cell response that may reduce viraemia [63]. Capripoxvirus expressing VP7 was shown to confer cross-protection [51]. Although vaccination with baculovirus-expressed BTV core-like-particles (CLP – containing VP3 and VP7) did not prevent clinical signs of the disease, it did reduce their severity [44]. The addition of expressed VP7 to vaccination antigens (with VP5Δ1–100 and soluble domains of VP2) failed to increase neutralising antibody titres (against BTV-4) and failed to protect IFNAR−/− mice from lethal challenge with BTV-8. Regardless of the antigen combination which we Entinostat used, there was no protection from the heterologous BTV-8 lethal challenge. These results show that the response to immunisations is serotype-specific and that VP2 is the main protective component in the three combinations of antigens. The results presented show that soluble BTV-VP2 domains and VP5 can be expressed in

bacteria, suggesting that they adopt a native conformation/fold in this system. The aim of this study was to assess bacterially-derived BTV structural-proteins as candidates for a DIVA-compatible subunit-vaccination-strategy, using Balb/c mice and the well-established BTV animal-model, IFNAR−/− mice. DIVA-compatible BTV vaccines could be based on a subset of the viral proteins, with detection of antibodies to the remaining protein(s) as surveillance markers for previous infections. Our results demonstrate potential for a bacterial-expressed BTV-subunit DIVA vaccine, based principally

on VP2 and VP5. The exclusion of VP7, which does not seem to influence protection, provides a mean for DIVA. The two expressed VP2 domains, VP2D1 and VP2D2 and combined on equimolar basis, generated high titres of neutralising antibodies with similar titres in both Balb/c and IFNAR−/−. Although a transient viraemia was observed in mice immunised with VP2D1 + VP2D2, post-challenge with BTV-4, this was rapidly cleared and they survived without signs of infection throughout the experiment. This indicates that soluble bacterial-expressed antigens are protective and do not require more complex eukaryotic expression systems. The use of bacterial-expressed protein antigens, could provide a safe and scalable alternative to live-attenuated BTV vaccines. Bacterial expression could represent an alternative to inactivated vaccines, particularly if viruses prove to be difficult to propagate in cell culture (like BTV-25 [7]).

This is consistent with the two trials (Kjellman and Oberg

2002, Viljanen et al 2003) that reported medium- (WMD –2, 95% CI –7 to 4) and long-term (WMD –0.1, 95% CI –6 to 6) pain outcomes. Pooled results from the two trials that reported disability outcomes (Kjellman and Oberg 2002, Viljanen et al 2003) from general strength and conditioning exercise showed no significant difference compared with minimal intervention at the conclusion of treatment (WMD 1, 95% CI –3 to 5) or medium- (WMD 1, 95% CI –3 to 5) or long-term (WMD –3, 95% Target Selective Inhibitor Library CI –7 to 2) follow-up. Manual therapy: In the three included trials of manipulation, there were four sham-controlled comparisons of the immediate analgesic effect of a single high-velocity manipulation. One trial ( Cleland et al 2005) investigated the effect of thoracic spine manipulation on neck pain and two trials ( Martinez-Segura et al 2006, Pikula 1999) investigated cervical spine manipulation. The three-arm trial by Pikula

and colleagues (1999) compared two different manipulation techniques with sham. The two manipulation groups in this trial were combined to create a single pair-wise comparison. Three trials click here ( Hemmila 2005, Hoving et al 2002, 2006, Skillgate et al 2007) were identified that compared manual therapy with minimal or no intervention. Pooled outcomes from three trials (Cleland et al 2005, Martinez-Segura et al 2006, Pikula 1999) show a significant analgesic benefit from a single manipulation compared with control (WMD –22, 95% CI –32 to –11). Medium- and longterm outcomes were not reported in these trials. Disability was not assessed. Pooled outcomes from two trials (Hoving et al 2002, Skillgate

et al 2007) show that manual therapy provided better pain relief after a course of treatment than minimal treatment (WMD –12, 95% CI –16 to –7). A similar benefit was not reported in the single trial (Hoving et al 2006) that reported medium- (MD –7, 95% CI –16 to 2) and long-term (MD –1, 95% CI –11 to 9) pain outcomes. Pooled outcomes from three trials (Hemmila 2005, Hoving et al 2002, Skillgate et al 2007) show that manual therapy resulted in significantly better disability mafosfamide outcomes at the conclusion of treatment than control (WMD –6, 95% CI –11 to –2). A similar benefit was not demonstrated in the two trials (Hemmila 2005, Hoving et al 2006) that reported medium- (WMD –8, 95% CI –24 to 7) and long-term (WMD –1, 95% CI –12 to 9) disability outcomes. Multimodal physical therapies: Two trials compared multimodal physical therapies, which included exercises, massage, and various electrotherapies, with minimal treatment. One trial excluded manual therapies ( Hoving et al 2002, 2006), and one trial included manual therapies ( Palmgren et al 2006) in the range of treatments provided.

7% (3465.55 ± 763 pg/ml) less MIP-2 was measured in the FomA-immunized mice ( Fig. 5C). Besides, CD11b, a prominent marker of inflammatory cells including macrophages was used to further analyze the severity of gum inflammation. A significant decrease in CD11b positive cells in swollen gum was detected in the FomA-immunized mice Akt targets compared to the GFP-immunized mice ( Supplementary Fig. 2). These results clearly demonstrate that vaccines targeting FomA efficiently prevent gum inflammation in mice caused by co-infection of F. nucleatum and P. gingivalis. F. nucleatum is one of the predominant organisms associated with halitosis, and this bacterium produces high levels

of VSCs [7]. The plaque biofilm is considered to be the principle source generating such VSCs [3]. Results in Fig. 1 indicated that co-aggregation of F. nucleatum with P. gingivalis augments biofilm formation. Thus, we next examined if bacterial co-aggregation could increase VSC production and if inhibition of F. nucleatum FomA can efficiently suppress the co-aggregation-induced VSC production. VSC production of F. nucleatum alone, P. gingivalis alone, and F. nucleatum plus P. gingivalis (4 × 109/104 CFU) were detected on lead acetate-contained agar

plates. F. nucleatum (4 × 109 CFU), but not P. gingivalis (104 CFU), produced VSCs ( Fig. 6A). The co-culture of F. nucleatum (4 × 109 CFU) with P. gingivalis (104 CFU) markedly enhanced VSC production ( Fig. why 6A), supporting the hypothesis that bacterial co-aggregation intensifies the emission of VSCs. To explore the involvement of FomA in VSC CAL-101 clinical trial production,

F. nucleatum was neutralized with either anti-FomA or anti-GFP serum [2.5% (v/v)] ( Fig. 3 and Fig. 4) and then co-cultured with P. gingivalis. After treatment with anti-FomA or anti-GFP serum, 104 CFU of P. gingivalis alone was insufficient to produce detectable VSCs although P. gingivalis has been shown to be a VSCs-producing bacterium [31]. The VSC production of F. nucleatum was slightly reduced after treatment with anti-FomA, but not anti-GFP serum ( Fig. 6B). After treatment with anti-GFP serum, co-aggregated F. nucleatum and P. gingivalis retained the capability of producing VSCs. In contrast, bacterial co-aggregation-induced VSC production was entirely suppressed when F. nucleatum was neutralized with anti-FomA serum ( Fig. 6B). This clearly demonstrates the ability of an antibody to FomA to prevent VSC production mediated by bacterial co-aggregation. Co-aggregation initiated by interaction and/or adherence of pathogenic bacteria is often an essential first step in the infectious process. The ability of oral bacteria to interact with one another, or to co-aggregate, may be an important factor in their ability to colonize and function as pathogens in the periodontal pocket [18]P. gingivalis and F.