To some extent, our understanding is limited by the methods used to detect and characterize multiple carriage. Ideally, a new method should detect multiple serotypes directly from the specimen (i.e., without a culture step which may alter the relative proportions of various strains) without

false positive reactions, and be quantitative, affordable, practical and capable of detecting all known serotypes. Although many potential methods have recently been developed they have not been sufficiently validated. The PneuCarriage project has compared 20 serotyping methods from 15 research groups, including their ability to detect multiple serotype carriage, using a well-characterized reference A-1210477 manufacturer bank of samples (Satzke et al., manuscript in preparation). This project will provide further information on suitable methods for detecting multiple serotype carriage with high sensitivity and specificity. Current methods routinely underestimate the prevalence of multiple serotype carriage. Although many new techniques are in development, there is insufficient evidence to make a recommendation. For studies where multiple carriage is relevant, we buy MLN0128 recommend retaining the original STGG specimens

for future assessment when optimal methods are defined. A thorough comparison of methods to detect NP carriage of multiple pneumococcal serotypes from pneumococcal cultures and directly from specimens is needed. The clinical and public health importance of multiple serotype carriage needs to be determined. Several storage methods, such as lyophilization, or ULT storage on commercially available

chemically-treated beads, are appropriate for long-term storage of pure pneumococcal isolates. However, our recommendations for storage of pneumococcal isolates in STGG media are consistent with the 2003 methods [1], but with some minor amendments to reflect the breadth of consensus practice. The storage of at least one tube of each pneumococcal isolate is recommended. To do this inoculate (using a swab or loop) a fresh, overnight, pure lawn culture into suitable media, such as STGG, under aseptic conditions. After ensuring the growth is homogenized, for example by a short vortex step, freeze at ULT. Short-term storage (<12 months) of these high-titer stocks at −20 °C in a non-defrosting freezer is acceptable, either although survival will decrease over this time [33] and [37]. To recover the isolate, a small amount of frozen material can be scraped from the surface of the STGG medium, or the entire volume thawed and an aliquot taken. The scraping or aliquot is then usually inoculated onto solid medium to check for purity of the isolate. Recovery of isolates should be undertaken aseptically, with a view to minimizing temperature fluctuations of the stored isolate by, for example, keeping tubes on dry-ice (or if necessary, and for short periods, wet ice) when handling them, and only processing a few tubes at a time.

Consistency of results was checked between different batches of assay antigen. The second batches of cCFP and TT appeared to produce slightly different cytokine responses. The second batch of cCFP was only used in a small number of samples,

which were therefore excluded from analysis. Epigenetics Compound Library cost However, the groups tested with different batches of TT were of similar size and therefore cytokine responses to TT were adjusted for TT batch to avoid loss of power. As different strains were administered during set periods of time in sequence according to their availability, there was potential for confounding by factors associated with both calendar time and cytokine responses (Table 1) [10]. Factors considered as a priori confounders were infant malaria parasitaemia, maternal Mansonella perstans and hookworm infection, and area of residence (as the recruitment area was gradually expanded to include more rural areas surrounding Entebbe and different environmental exposures may influence cytokine responses). All analyses were adjusted for the above factors as well as HIV infection, which causes severe restriction of infant cytokine responses [10] and [36]. As anthelminthic treatment allocation was randomised and was found to have no effect on NVP-BKM120 price infant immune responses [30], maternal anthelminthic was not considered as a possible confounder, or adjusted Electron transport chain for, in this analysis. Mortality

rates per 1000 person years were compared between strain groups using Cox regression hazard ratios. The numbers of BCG-related adverse events were tabulated by group and compared using Fisher’s exact test. All mothers gave informed, written consent. Ethical approval for the trial was granted from the Science and Ethics Committee of the Uganda Virus Research Institute, Uganda National Council for Science and Technology, and London School of Hygiene and

Tropical Medicine. Of 2345 livebirths, 2081 singleton babies received BCG at Entebbe Hospital within 6 months of birth. Of these, 145 infants did not have data on immunisations other than those administered at birth; 220 infants did not receive all three doses of tetanus toxoid; 60 infants died or were lost to follow-up before 1 year of age; 315 infants were still in follow-up but did not provide a blood sample within the specified time frame. Therefore 1341 samples with immunological results were eligible for this analysis. Mothers of infants not included were in earlier stages of gestation at recruitment, younger, and more likely to be first-time mothers, of lower socio-economic status and living in a more distant study area [30]. However, lack of eligibility was not associated with strain group. The three groups had similar socio-demographic characteristics (Table 1); there were however differences in maternal hookworm and M. perstans infection prevalence.

These features, together with their capacity to efficiently adsorb protein Ags, to be readily internalized by APC, and to enhance immune responses to Ag both in vitro and in vivo, make them good potential delivery systems for vaccines, and in particular that of HIV vaccines for the developing world. Manipulation of the YC-wax NP surface charge with surfactants, provides optimal flexibility to adsorb different types of Ag [30]. In this study, Ags as diverse as TT, BSA, and HIV-1 gp140 were efficiently adsorbed to both negatively and positively charged NP. In addition, the surface charge flexibility also facilitated

co-adsorption of more than one molecule onto the NP surface as shown by co-adsorption Ku-0059436 solubility dmso of Ag with CpGB and PolyI:C. After screening a large range of wax NP, three different types

were selected according to their low toxicity, Ag adsorption efficiency, and cell internalization profile, i.e., YC-SDS, YC-NaMA, and YC-Brij700-chitosan. The first two NP had a net negative charge, whereas the third one was highly positive, a characteristic defined by the presence of the carbohydrate chitosan. We determined adsorption of gp140 to these NP by three different methods: Z potential, Bradford assay, and ELISA. All three methods provided strong evidence of effective Ag adsorption to NP. In addition, the ELISA assay Selleckchem beta-catenin inhibitor suggested that antigenicity was unaffected, which may represent an advantage over Ag encapsulation as reported previously for a form of HIV-gp120 by Singh et al. [31]. Flow cytometry and confocal microscopy studies clearly showed that Ag-adsorbed YC NP were readily internalized by APC, and that these NP were subsequently tracked within endolysosomes, suggesting that the NP may have the capacity to deliver Ag into the Ag processing ADAMTS5 and presentation compartment. Naked YC-wax NP did not induce cytokine/chemokine production or up-regulation of co-stimulatory molecules on DC in vitro, nor induced visible signs of inflammation after both mucosal and systemic administration in vivo (data not shown). This lack of DC activation by naked NP is important especially if used at the urogenital tract,

because such cell activation would induce mucosal inflammation at this level that may facilitate HIV infection. Antigen-adsorbed YC-wax NP (TT in human PBMC and gp140 in mouse splenocytes) enhanced T-cell proliferation responses in vitro. The response to TT by human PBMC was greatly enhanced by co-adsorption with CpGB (Fig. 3B) but not with PolyI:C (data not shown). CpGB on its own enhanced cellular proliferation, and we speculate that CpGB induces non-specific proliferation of PBMC most likely due to polyclonal B cell activation, as has been described previously [32]. Nevertheless, the enhanced proliferation observed with co-adsorption of TT + CpGB particles was significantly greater than the additive effect of TT plus CpGB alone.

In Norway a diagnostic cut-off of anti-PT IgG level at 80 IU/ml is recommended (established with the Virion\Serion Bordetella Pertussis Toxin IgG assay). Within the first 2 years after the booster only 9 of 130 subjects had anti-PT IgG values above this level; however, 4 of these also had an anti-Prn IgG level above 50 IU/ml possibly indicating recent infection with B. pertussis. Antibodies against pertussis vaccine antigens were measured in a cross-sectional study in sera from children aged 6–12 years. Most of the children received a DTaP booster vaccine at age 7–8 years. At 6.4 geometric mean years after

primary vaccination, the pre-booster anti-PT IgG GM level was 7.3 IU/ml. In the first 100 days after the booster dose a rather moderate peak response was observed reaching up to an PS341 anti-PT IgG GM level of 45.6 IU/ml, which was followed Selleckchem Epacadostat by a subsequent decline the following years. Three years after the booster dose almost 20% of the sera contained an anti-PT

IgG level less than 5 IU/ml. These anti-PT IgG levels are lower than the corresponding levels reported in a Danish study where adults were given a booster vaccine with a single-component pertussis antigen (PT), in spite of the lower PT-antigen content in the Danish vaccine [10]. Also, in a Dutch study using an aP booster vaccine with a similar dose of PT and FHA [19], higher anti-PT IgG levels (187 EU/ml 28 days post booster) were found than we did in our study. The shorter interval between primary immunisation series and the booster dose in the Dutch study (4 years versus 6 years) and the shorter and exact blood sample timing after the booster (28 days versus 0–100 days (mean 59 days)) might possibly explain the more pronounced booster response. In line with our results they also noted a significant decline in the anti-PT IgG level 2 years after the booster.

Caution should nevertheless be taken when results from different laboratories are compared; however the methods used are similar and have been compared through inter-laboratory evaluations. The differences observed are more likely explained by different those vaccine history, different vaccines, different age groups, and possible interference from other vaccine antigens. In line with the decrease of pertussis-specific antibodies, a higher number of sera with an anti-PT IgG level ≤5 IU/ml were found with increasing time since booster. Although there is no established serological correlate of protection against pertussis, it is likely that subjects with low vaccine-induced anti-PT IgG levels are less protected than subjects with higher levels [20] and [21].

Cause of death was therefore considered as unknown, although it cannot be excluded that the animal died due to RVFV infection. Statistical comparison of the detected RVFV RNA levels between goats inoculated with Vero E6-produced virus (n = 12) and goats inoculated with C6/36 cells-produced virus (n = 16) indicated that the developed viremia was higher with faster onset in animals infected

with insect cell-derived virus (P = 0.002) ( Fig. 4A). When the dose 107 PFU/animal of virus of either origin was evaluated separately, the insect-derived virus caused faster onset of the viremia, with the significantly higher RNA levels at 1 dpi (P < 0.001) cAMP inhibitor ( Fig. 4B). Increase in rectal temperature can be used as one of the parameters in challenge studies in sheep to evaluate efficacy of the vaccine learn more candidates, but is unfortunately not applicable for goats. All RVFV inoculated lambs experienced minimum one or two days of increased rectal temperatures, with no significant differences between individual inoculation

approaches (Fig. 5). On the other hand, out of all 28 RVFV inoculated goats only 11 random animals developed increased rectal temperatures for one day. Although antibody development was not the main focus of the study, due to limited knowledge on RVFV infection in goats, the animals were kept for 28–30 dpi, and serum collected during the animal inoculation experiments was analyzed by plaque reduction neutralization assay. Development of neutralizing antibodies against RVFV in goats is summarized in Fig. 6. Significant difference in antibody titers, related to inoculation Thymidine kinase dose, was observed at 14 dpi. Animals infected with 107 PFU of either Vero E6 or C6/36 cell-produced virus developed at least four-fold higher antibody titers than goats infected with

105 PFU, however a continuous gradual increase in antibody titers until the end of the experiment was observed in serum of animals inoculated with the lower dose. Very interestingly, goats infected with high dose of mosquito cell-produced virus experienced a drop in neutralizing titers by 28 dpi, while goats infected with the Vero E6 cell-produced RVFV maintained their antibody levels at 21 dpi also at 28 dpi. A difference in the onset of antibody response was observed between goats and sheep. While serum samples collected at 4 dpi were all negative, first neutralizing antibodies were detected at 5 dpi in 92.5% of goats, and on day 6 post infection all goats seroconverted. In comparison, only 85% of sheep seroconverted at 6 dpi, with all serum samples collected at 7 dpi being positive for neutralizing antibodies. The antibody titers at 7 dpi for both, goats and sheep were about the same, in range of 20–40, for all the animals.

However, the reduction in frequency was significantly greater in the experimental Alectinib cost group, by a mean of 1.2 cramps per night (95% CI 0.6 to 1.8). The severity of nocturnal leg cramps did not improve at all in the control group. However, there was a substantial reduction in the experimental group. The mean difference in improvement in the severity of the nocturnal leg cramps was

1.3 cm on the 10-cm visual analogue scale. No adverse events were reported in either group. Our results showed that six weeks of nightly stretching of the calf and hamstring muscles significantly reduced the frequency and severity of nocturnal leg cramps in older people. The best estimate of the average effect of stretching on the frequency of cramps was a reduction of about one cramp per night. Given that participants had an average of approximately three cramps per night at the beginning of the study, this is a substantial effect and approximately equal to the effect we nominated as worthwhile. Since the stretches are quick and simple to perform, some patients may even consider the weakest effect suggested by buy Pifithrin-�� the limit of the confidence interval (a reduction of 0.6 cramps per night) to be worthwhile. The stretches reduced the severity

of the pain that occurred with the nocturnal leg cramps by 1.3 cm on a 10-cm visual analogue scale. We do not know the smallest effect on the severity of the cramps that patients typically feel would make the stretches worthwhile. In other research using the 10-cm visual analogue scale for pain, a change score of 2 cm has been proposed in chronic low back pain patients (Ostelo and de Vet, 2005). An effect of this magnitude was not achieved in our study within the 6-week intervention period. However, the confidence interval around this result is reasonably

narrow. Therefore patients can be advised that the average effect of the stretches is to reduce the severity of the pain by 1.3 cm on the 10-cm scale (or close to this value). Patients can then decide for themselves whether this effect – in addition to the reduced ALOX15 frequency of the cramps – makes the stretches worth doing. In this trial, stretching was performed at home and was patient-centred. This facilitated performance of the intervention, which may have aided adherence with the stretches and increased the effectiveness of the intervention. In this setting, however, correct execution of the stretching technique was not closely monitored. All the participants in the experimental group did two exercises, regardless of whether the cramp was located in the hamstrings or calf. Greater effects may perhaps be achievable if stretches were to be targeted at the site(s) of each participant’s cramps. This could be investigated in a future trial.

5B), likewise, an increase in CLint,P-gp resulted in a small increase on the FG ( Figs. S6–7B). These changes were dependent of both release rate and BCS classification, as the increase in fa was more prominent for IR formulations of BCS class 2 compounds ( Figs. 5B and S5B), whereas the impact of CLint,P-gp on FG was perceptible only for IR formulations of BCS class 1 compounds ( Fig. S6A). Analysis of the

relative bioavailability (Frel) of CR formulations showed that highly (CYP3A4) cleared BCS class 1 simulated compounds could display up to a 220% higher Frel compared to the IR formulations. When the trends for the simulations were compared with similar compounds derived from the literature survey, i.e., BCS class 1 and mainly CYP3A4 cleared, Nintedanib there was a very good agreement between the simulated Frel and the observed data ( Fig. 6). The back-calculated CYP3A4 clearance values (HLM)

BMN673 from the in vivo systemic clearance are reported in Table S3 of the Supplementary Material. Due to the selected inclusion criteria for the search, the analysis was limited only to 11 different compounds (Fig. 2). A larger set of drugs could have been included for this analysis if, for instance, the calculations of relative bioavailability were performed between different subjects and groups, i.e., the IR data was taken from one study whereas the CR data was taken from a separate study. However, this would have confounded the impact of the formulation with the inter-individual variability of the kinetics, leading to variable Frel. Therefore these studies were not considered. Of the total drugs investigated, only three drugs formulated as CR showed statistically significant higher relative bioavailability than their IR formulations (simvastatin, buspirone and oxybutynin). In contrast, a majority of the drugs showed either similar or lower relative bioavailability

Resminostat when formulated as CR. Judging from the BCS point of view an a priori trend for either higher of lower Frel was not clear. For instance CR formulations of fluvastatin (BCS class 1) and simvastatin (BCS class 2), both highly permeable compounds, showed opposite results in terms of Frel ( Fig. 2). Whereas CR formulations of low permeable compounds, such as propiverine and gepirone (both BCS class 3), showed similar Frel to their IR formulations. Therefore this justified the use of more mechanistic and multivariate models such as PBPK for M&S purposes in order to accommodate several factors influencing the observed differences. A general trend towards a reduction in drug exposure (AUC) was observed in simulations when varying the release rate, i.e., moving from an IR formulation to a CR formulation. These results were anticipated as, in general the CR formulations are intended to release the majority the drug content further distally in the intestine (e.g.

20 mg), C-DIM-8 (50 ± 5.36 mg), C-DIM-5 + doc (46 ± 3.47 mg) and C-DIM-8 + doc (45 ± 5.20 mg) compared to vehicle (100 ± 6.84 mg) ( Fig. 6A). Decreased tumor growth based on volumes was also significantly (p < 0.05) decreased in the treated compared to control mice ( Fig. 6B). A relative mean tumor volume of 150 ± 8.90 mm3 was observed in the control mice, and tumor volume decreased following treatment with doc (66.67%; 50 ± 4.77 mm3), C-DIM-5 (65.33%; 52 ± 4.80 mm3), C-DIM-8 (62.67%; 56 ± 5.80 mm3), C-DIM-5 + doc (74.67%; 38 ± 4.20 mm3), and C-DIM-8 + doc (70.67%; 44 ± 3.80 mm3) ( Fig. 6B). C-DIM-5 and C-DIM-8 nebulized formulations inhibited VEGF expression in A549 lung tumor when given alone and when combined

with doc ( Fig. 7A). This was observed as positive (dark brown) immunohistochemical Selleckchem Sirolimus staining for VEGF on lung sections. Quantification of VEGF-positive cells was represented as percentage of the mean normalized against control ( Fig. 7B). The results showed

a decrease in VEGF staining following treatment with doc (68 ± 5.82%; Fig. 7A-II), C-DIM-5 (49 ± 5.30%; Fig. 7A-III), C-DIM-8 (54 ± 5.83%; Fig. 7A-IV), C-DIM-5 + doc (26 ± 4.25%; Fig. 7A-V) and C-DIM-8 + doc (28 ± 4.02%; Fig. 7A-VI) compared to control ( Fig. 7A-I). The decrease in VEGF expression was significant across all treatment groups relative to control and between the single and combination treatments of the same compounds (p < 0.05). However, the differences SB203580 in VEGF expression between C-DIM-5 and C-DIM-8 and between their combinations were not significant ( Fig. 7B). Microvessel density (MVD) was determined by immunopositive staining for CD31 (Fig. 7C). Tissue sections stained dark brown for CD31 with a progressive decrease in staining observed for sections from the treatment groups compared to the control. MVD assessment of sections showed significant reduction (p < 0.05) in MVD in the groups treated with doc (182 ± 10.28 microvessels/mm2;

Fig. 7C-II and D), C-DIM-5 (164 ± 15.31 microvessels/mm2; Fig. 7 C-III and D), C-DIM-8 (158 ± 10.85 microvessels/mm2; Fig. 7 C-IV and D), C-DIM-5 + doc (106 ± 9.50 microvessels/mm2; Fig. 7 C-V and D), and C-DIM-8 + doc (118 ± 11.07 microvessels/mm2; Fig. 7C-VI and D) compared to 248 ± 25.11 microvessels/mm2 in the control ( Fig. 7C-I and D). Treatment-related already induction of apoptosis was determined by TUNEL staining which showed positive staining for DNA fragmentation as dark-brown or reddish staining (Fig. 8A). Compared to the untreated control group (Fig. 8B), there was significantly increased (p < 0.05) DNA fragmentation in mice treated with doc (38 ± 4.02%), C-DIM-5 (56 ± 6.20%) and C-DIM-8 (60 ± 5.40%), combination treatment of C-DIM-5 + doc (78 ± 8.11%) and C-DIM-8 + doc (80 ± 8.90%). Positive staining for TR3 was evident as dark-brown staining (Fig. 8C). The pattern of TR3 expression following immunostaining was similar in intensity and was evident of nuclear localization in all groups.

Renal uptake and retention of radiopharmaceuticals are dependent not only on the characteristics of the targeting molecule, but also on the

type of radionuclide and chelating agent Alectinib used. We observed that the renal uptake levels of 111In-DOTA-RAFT-c(-RGDfK-)4 and 64Cu-cyclam-RAFT-c(-RGDfK-)4 were substantially different, with biodistributions at 24 h after injection of ∼40%ID/g and ∼10%ID/g, respectively [6] and [19]. Therefore, in this study, we determined the effect of GF on the renal uptake and retention of 64Cu-cyclam-RAFT-c(-RGDfK-)4 in normal and tumor-bearing mice. In comparison with the published work on the 111In-labeled analog, the present study particularly evaluated (1) the dose–effect relationship

of GF, (2) the combined effect of GF and Lys, (3) the spatiotemporal changes in renal radioactivity caused by GF in the presence or absence of Lys (GF ± Lys), and (4) the influence Epacadostat of GF ± Lys on the metabolism of 64Cu-cyclam-RAFT-c(-RGDfK-)4. Another novelty is that the present study explored the mechanisms underlying the action of GF and Lys using the noninvasive and quantitative PET imaging technology. Cyclam-RAFT-c(-RGDfK-)4 (MW 4119.6) was synthesized as reported previously [5], and radiolabeled with 64Cu in accordance with our previous report [6] with minor modifications. In brief, 0.08 mM cyclam-RAFT-c(-RGDfK-)4 in dimethyl sulfoxide and 1.48 MBq/μL 64CuCl2 in ammonium citrate buffer (100 mM, pH 5.5) were mixed in a ratio of 1:1 (v/v) and incubated at 37 °C for 1 h. The radiolabeling efficiency, as determined by reversed phase (RP) high-performance

liquid chromatography, was >98%, and the specific radioactivity was ∼18.5 MBq/nmol. Gelofusine (Braun Medical, Oss, Netherlands), below kindly provided by Dr. Lucie Sancey (University of Lyon 1, France), consists of a 40 g/L solution of succinylated gelatin for intravenous infusion, and was diluted in normal saline (NS) for use in the present study. l-Lysine (Sigma–Aldrich, Buchs, Switzerland) was dissolved in NS and added to the injectate prior to administration. Human glioblastoma U87MG cells naturally expressing αVβ3 were cultured as previously described [6]. Animal procedures were approved by Institutional Animal Care and Use Committee of the National Institute of Radiological Sciences (NIRS; Chiba, Japan). Normal or tumor-bearing mice (female BALB/cAJcl-nu/nu; CLEA Japan, Inc., Tokyo, Japan) at 7–8 weeks of age were examined. The tumors, 7–10 mm in diameter, were developed by subcutaneous (s.c.) injection of 1 × 107 cells into the left shoulder region of the mice. Mice were injected via tail vein (i.v.) with 0.74 MBq 64Cu-cyclam-RAFT-c(-RGDfK-)4 with or without co-injection of GF, Lys, or both (GF + Lys). The biodistribution study consists of the following 3 sequential experiments.

1). In many comparisons, the difference between LAIV and placebo recipients was statistically significant. In study 3, responses were observed after a single dose but the differences compared to placebo recipients were more apparent after receipt of 2 doses of vaccine. Among subjects receiving only 1 dose of vaccine in year 1, a

greater difference versus placebo was observed at FXR agonist the second versus first sample collection (approximately 2 months versus 1 month postvaccination). When the percentage of subjects with a ≥4-fold increase was evaluated, a similar pattern was observed, although response rates were lower. For LAIV and placebo recipients respectively, response rates were 26–39% versus 12–30% for A/H1N1, 33–48% versus 20–27% for A/H3N2, and 46–59% versus 14–38% for B. When subjects were stratified by baseline

serostatus, similar IgA responses were observed among seronegative and seropositive subjects. Postvaccination GMFRs for strain-specific IgA ratios among LAIV recipients after 2 doses of vaccine in year 1 ranged from 1.4 to 6.2, compared to 0.5–2.0 among placebo recipients (Table 1). In year 2, GMFRs ranged from 1.2 to 4.6 among LAIV recipients and 0.8–2.2 among placebo recipients (Table 1). Postvaccination GMFRs in absolute strain-specific IgA, uncorrected for total IgA, trended higher than postvaccination selleck chemicals GMFRs in strain-specific IgA ratios. Among LAIV and placebo recipients, total IgA increased from prevaccination to postvaccination by 1.0- to 2.4-fold in year 1 and 0.7- to 1.2-fold in year 2 (Table 2). Year 1 of study 3 was responsible for the greatest observed responses for LAIV and placebo recipients and 4 of the 5 statistically significant GMFRs. Because of the observed increases in total IgA from prevaccination to postvaccination in both placebo and vaccine recipients in year 1 of study 3, subject-level data by site were reviewed. In study 3, but not in studies 1 and 2, the total IgA content in year 1 prevaccination samples was lower among the initial subjects enrolled

at sites and higher among subjects enrolled subsequently; the linear regression analysis controlling for site showed that total IgA content in prevaccination samples increased significantly over calendar time in study 3 (P = 0.002). Across studies, data for both HAI and IgA responses following receipt of 2 doses was available for 392 LAIV recipients and 213 placebo recipients in year 1. Four-fold increases in HAI antibody titer for A/H1N1 were observed for 61% of LAIV recipients compared to 13% of placebo recipients (P < 0.001); for A/H3N2 and B, responses were 74% versus 16% (P < 0.001) and 76% versus 12% (P < 0.001) for LAIV versus placebo recipients, respectively. Among LAIV recipients, IgA responses were more frequently seen among subjects with an HAI response. Across studies, IgA responses to A/H1N1 were observed among 48% of subjects with a 4-fold HAI response, compared to 33% of those without a 4-fold HAI response (P < 0.001).