Safety of classical swine fever virus vaccine strain LOM in pregnant sows and their offspring

The present study aimed to evaluate the safety of the classical swine fever virus (CSFV) vaccine strain LOM in pregnant sows. Pregnant sows with free CSFV antibody were inoculated with a commercial LOM vaccine during early pregnancy (day 38; n = 3) or mid-pregnancy (days 49–59; n = 11). In pregnant sows vaccinated during the early stages of gestation, abortion (day 109) was observed in one case, with two stillbirths and seven mummified fetuses. The viability of live-born piglets was 34.9% in sows vaccinated during mid-pregnancy compared with 81.8% in the control group. Post-mortem examination of the organs of the sows and piglets did not reveal any pathological lesions caused by CSFV; however, CSFV RNA was detected in the organs of several vaccinated sows and their litters. The LOM strain was transmitted from sows with free CSFV antibody to their fetus, but did not appear to induce immune tolerance in the offspring from vaccinated pregnant sows. Side effects were not observed in pregnant sows with antibody to the LOM strain: transmission from sow to their litters and stillbirth or mummified fetuses. The LOM strain may induce sterile immunity and provide rapid, long-lasting, and complete protection against CSFV; however, it should be contraindicated in pregnant sows due to potential adverse effects in pregnant sows with free CSFV antibody.     

Self-administration of intranasal influenza vaccine: Immunogenicity and volunteer acceptance

BackgroundIn outbreak settings, mass vaccination strategies could maximize health protection of military personnel. Self-administration of live attenuated influenza vaccine (LAIV) may be a means to vaccinate large numbers of people and achieve deployment readiness while sparing the use of human resources.MethodsA phase IV, open-label, randomized controlled trial evaluating the immunogenicity and acceptance of self-administered (SA) LAIV was conducted from 2012 to 2014. SA subjects were randomized to either individual self-administration or self-administration in a group setting. Control randomized subjects received healthcare worker-administered (HCWA) LAIV. Anti-hemagglutinin (HAI) antibody concentrations were measured pre- and post-vaccination. The primary endpoint was immunogenicity non-inferiority between SA and HCWA groups. Subjects were surveyed on preferred administration method.ResultsA total of 1077 subjects consented and were randomized (529 SA, 548 HCWA). Subject characteristics were very similar between groups, though SA subjects were younger, more likely to be white and on active duty. The per-protocol analysis included 1024 subjects (501 SA, 523 HCWA). Post-vaccination geometric mean titers by vaccine strain and by study group (HCWA vs. SA) were: A/H1N1 (45.8 vs. 48.7, respectively; p = 0.43), A/H3N2 (45.5 vs. 46.4; p = 0.80), B/Yamagata (17.2 vs. 17.8; p = 0.55). Seroresponses to A components were high (∼67%), while seroresponses to B components were lower (∼25%). Seroresponse did not differ by administration method. Baseline preference for administration method was similar between groups, with the majority in each group expressing no preference. At follow-up, the majority (64%) of SA subjects preferred SA vaccine.ConclusionsLAIV immunogenicity was similar for HCWA and SA vaccines. SA was well-tolerated and preferred to HCWA among those who performed SA.     

An internet-delivered exercise intervention for workplace health promotion in overweight sedentary employees: A randomized trial

ObjectiveTo evaluate the effect of structured vs. non-structured internet-delivered exercise recommendations on aerobic exercise capacity and cardiovascular risk profile in overweight sedentary employees.Methods140 employees of an automobile company (11% female, median age 48 years (range 25–60), BMI 29.0 kg/m² (25.0–34.8)) were randomized in a 3:2 ratio to an intervention group receiving structured exercise schedules or a control group choosing workouts individually via an interactive website. The 12-week intervention took place in Munich, Germany, during summer 2008. Main outcome measure was performance at the lactate anaerobic threshold (P_AT/kg) during ergometry.Results77 participants completed the study. The intervention group (n = 50) improved significantly in P_AT/kg ((mean (SD)) 1.68 (0.31) vs. 1.81 (0.33) W/kg; p = 0.002), VO₂peak (3.21 (0.63) vs. 3.35 (0.74) L/min; p = 0.04), and waist circumference (100.5 (7.9) vs. 98.0 (7.8) cm; p = 0.001). The control group (n = 27) improved significantly in P_AT/kg (1.59 (0.38) vs. 1.80 (0.49); p < 0.001) and waist circumference (101.9 (8.7) vs. 98.3 (8.5) cm; p < 0.001), but not in VO₂peak. No significant between group differences in these outcome measures were noted.ConclusionStructured, internet-delivered exercise recommendations are not superior to internet-delivered non-structured exercise recommendations in a workplace setting. Both lifestyle intervention strategies are, however, limited by high dropout rates.     

Hepatitis B vaccination uptake and correlates of serologic response among HIV-infected and uninfected men who have sex with men (MSM) in Bangkok,Thailand

BackgroundVaccination against hepatitis B virus (HBV) is recommended for all HBV-susceptible men who have sex with men (MSM). There is limited information on correlates of immunity to HBV vaccination in this group. We present serologic response rates to hepatitis B vaccine and identify factors associated with impaired response among HIV-uninfected and HIV-infected Thai MSM.MethodologyHBV-susceptible volunteers were offered hepatitis B vaccination at months zero, one, and six. We measured baseline (pre-vaccination) total serum IgG and IgG subclasses (all participants), baseline CD4 count, and plasma HIV-1 viral load (PVL) (HIV+ participants). HBV serologies were retested at 12 months. Serologic responses were compared between all groups in men receiving three vaccine doses.Results511/651 HIV-negative and 64/84 HIV-positive participants completed the three-dose series. Response rates in HIV-uninfected and -infected participants were 90.1% vs. 50.0% (p < 0.0001). Median pre-vaccination IgG was higher among non-responders than responders overall (1238.9.0 vs. 1057.0 mg/dL, p = 0.003) and among HIV-infected participants (1534.0 vs. 1244.5 mg/dL, p = 0.005), but not significantly among HIV-uninfected participants (1105.5 vs. 1054.3 mg/dL, p = 0.96). Pre-vaccination IgG1 and IgG3 levels were higher among HIV-positive than HIV-negative participants (median 866.0 vs. 520.3, and 105.8 vs. 83.1 mg/dL, respectively, p < 0.0001). Among HIV-infected participants, median CD4 count in non-responders was 378 cells/μL vs. 431 cells/μL in responders (p = 0.20). Median PVL in non-responders was 64,800 copies/mL vs. 15500 copies/mL in responders (p = 0.04). Participants with pre-vaccination plasma IgG >1550 mg/dL and PVL >10,000 copies/mL were almost always non-responsive (p < 0.01).ConclusionsHIV infection was associated with poor vaccine responses. High plasma viral load, elevated pre-vaccination total serum IgG and elevated pre-vaccination IgG1 are associated with poorer response to vaccination among HIV-infected MSM. In this group, the combination of high PVL and pre-vaccination total IgG is highly predictive of vaccine failure.     

Factors affecting the causality assessment of adverse events following immunisation in paediatric clinical trials: An online survey

BackgroundSerious adverse events (SAEs) in clinical trials require reporting within 24 h, including a judgment of whether the SAE was related to the investigational product(s). Such assessments are an important component of pharmacovigilance, however classification systems for assigning relatedness vary across study protocols. This on-line survey evaluated the consistency of SAE causality assessment among professionals with vaccine clinical trial experience.MethodsMembers of the clinical advisory forum of experts (CAFÉ), a Brighton Collaboration online-forum, were emailed a survey containing SAEs from hypothetical vaccine trials which they were asked to classify. Participants were randomised to either two classification options (related/not related to study immunisation) or three options (possibly/probably/unrelated). The clinical scenarios, were (i) leukaemia diagnosed 5 months post-immunisation with a live RSV vaccine, (ii) juvenile idiopathic arthritis (JIA) 3 months post-immunisation with a group A streptococcal vaccine, (iii) developmental delay diagnosed at age 10 months after infant capsular group B meningococcal vaccine, (iv) developmental delay diagnosed at age 10 months after maternal immunisation with a group B streptococcal vaccine.ResultsThere were 140 respondents (72 two options, 68 three options). Across all respondents, SAEs were considered related to study immunisation by 28% (leukaemia), 74% (JIA), 29% (developmental delay after infant immunisation) and 42% (developmental delay after maternal immunisation). Having only two options made respondents significantly less likely to classify the SAE as immunisation-related for two scenarios (JIA p = 0.0075; and maternal immunisation p = 0.045). Amongst study investigators (n = 43) this phenomenon was observed for three of the four scenarios: (JIA p = 0.0236; developmental delay following infant immunisation p = 0.0266; and developmental delay after maternal immunisation p = 0.0495).ConclusionsSAE causality assessment is inconsistent amongst study investigators and can be influenced by the classification systems available to them. There is a pressing need for SAE classification systems to be standardised across study protocols.     

Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection

Chemokines and chemokine receptors are crucial for immune response in HIV-1 infection. Although many studies have been done to investigate the relationship between chemokines and chemokine receptor gene polymorphisms and host’s susceptibility to HIV-1 infection, the conclusions are under debate. In the present study, a cohort of 287 HIV-1 seropositive patients, 388 ethnically age-matched healthy controls and 49 intravenous drug users (IDUs) HIV-1 exposed seronegative individuals (HESN) from Chinese Han population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. Seven polymorphisms on four known chemokines/chemokine receptor genes (CCR5Δ32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES −403A/G, RANTES −28C/G and SDF1 3′-A) were screened. CCR5Δ32 and CCR5 m303 were absent or infrequent in Chinese Han population, which may not be hosts’ genetic protective factors for HIV-1 infection. Our results showed the CCR5 59029A/G, CCR2 64I and SDF1 3′-A were not associated with host’s resistance to HIV-1 infection. The frequency of RANTES −403A allele was significantly lower in HIV-1 patients than in healthy blood donors (p = 0.0005) and HESN group (p = 0.035), which implied the association between A allele and reduced HIV-1 infection risk. Different genetic models were assessed to investigate this association (AA vs. GG + AG, OR = 0.38 95% CI, 0.22–0.65 p = 0.0004; A vs. G, OR = 0.66 95% CI, 0.52–0.84 p = 0.0006), which supported this association, either. The genotype and allele distribution of RANTES −28 between HIV-1 patients and healthy controls (genotype profile: p = 0.072; allele profile: p = 0.027) or HIV-1 seronegative group (genotype profile: p = 0.036; allele profile: p = 0.383) were both at the marginal level of significance, which were not observed after Bonferroni correction. All these results suggest the RANTES −403A may be associated with reduced susceptibility to HIV-1 infection, while the RANTES −28 locus not. By lack of the patients’ clinical information, whether these polymorphisms affect AIDS disease progression and their role in different HIV-1 infection routes could not performed in present study and needs to be assessed in ongoing studies.     

Association between SNPs in miRNA-machinery genes and chronic hepatitis B in the Chinese Han population

Single nucleotide polymorphisms (SNPs) in miRNA-machinery genes can influence their generation and maturation, then expression and structure. To explore the relationship between three SNPs (rs3757 in DGCR8, rs636832 in AGO1, rs7813 in GEMIN4) in miRNA-machinery genes and chronic hepatitis B, we genotyped the SNPs by high resolution melting method (HRM) in a case-control study of 332 unrelated chronic hepatitis B patients and 352 unrelated healthy controls in Western China. Interestingly, the rs636832 was significantly associated with the susceptibility of CHB (genotype: AA/GA/GG: p = 0.010; allele: A/G: OR = 0.727, 95% CI = 0.575–0.920, p = 0.008). The minor allele A of rs636832 was significantly associated with a decreased risk of CHB. Additionally, the dominant model AG + GG vs. AA showed a risk of 1.442-fold (p = 0.018) with CHB. Further exploration for the association between rs636832 and HBV-DNA load in 329 cases showed no significant difference (genotype: p = 0.321; allele: p = 0.148). Neither did the association between rs636832 and the status of HBsAg and HbeAg (HBsAg: genotype p = 0.337, allele p = 0.436; HBeAg: genotype p = 0.861, allele p = 0.822). Our study first provided the evidence that rs636832 in AGO1 was associated with chronic HBV infection susceptibility in Chinese Han population. Further epidemiological and functional studies in larger populations are warranted to verify our results.     

Hepatitis B vaccine alone may be enough for preventing hepatitis B virus transmission in neonates of HBsAg (+)/HBeAg (−) mothers

Background and aimTo prospectively evaluate the efficacy of vaccine alone compared with vaccine plus HBIG for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (−) mothers.MethodsCombined immunization is currently recommended for neonates of HBsAg (+) mothers in China. As a result, a randomized design is infeasible due to ethical reasons. In practice, Guangxi Zhuang Autonomous Region and Jiangsu Province implement vaccine alone and vaccine plus HBIG strategies for neonates born to HBsAg (+)/HBeAg (−) mothers, respectively. We alternatively enrolled neonates of HBsAg (+)/HBeAg (−) mothers from these two regions. Three doses of a recombinant yeast-derived hepatitis B vaccine were given at 0, 1 and 6 months with or without HBIG at birth.ResultsAt 7 months, sera were collected from 132 neonates in Guangxi Zhuang Autonomous Region and 752 neonates in Jiangsu Province. Baseline characteristics of both mothers and neonates were comparable in the two regions. No differences were revealed regarding the occurrence of perinatal HBV transmission with or without HBIG at birth [0.1% (1/752) vs. 0.0% (0/132), p = 1.000]. The anti-HBs response rates were 97.7% (129/132) and 98.5% (740/751) for the neonates with vaccine alone and with HBIG (p = 0.758), respectively. Vaccine alone induced a significantly higher anti-HBs GMC as compared to vaccine plus HBIG at 7 months of age (1555.3 mIU/mL vs. 654.9 mIU/mL, p < 0.0001). At 12 months of age, protective levels of anti-HBs remained in 97.4% (596/612) and 98.3% (118/120) of the neonates receiving and not receiving HBIG, respectively (p = 0.771). The neonates receiving combined prophylaxis had a markedly lower anti-HBs GMC (210.7 mIU/mL vs. 297.0 mIU/mL, p = 0.011). Horizontal HBV transmission occurred in none of the successfully immunized neonates for both compared groups at 12 months of age.ConclusionsVaccine alone may be enough for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (−) mothers.     

Factors related to vaccine uptake by young adult women in the catch-up phase of the National HPV Vaccination Program in Australia: Results from an observational study

BackgroundAustralia commenced a publically-funded, National Human Papillomavirus (HPV) Vaccination Program in 2007 with a two year catch-up phase for females aged 12–26 years.ObjectiveTo identify the factors associated with the uptake of the HPV vaccine (which has a recommended 3-dose schedule in Australia) by young adult women vaccinated by general practitioners and community-based programs within the catch-up phase.Methods1139 women who were eligible to receive the free HPV vaccine during the catch-up period were recruited in 2008–2009 (age 20–29 years at recruitment), in New South Wales, after having a normal (negative) cervical smear result recorded on the NSW Pap Test Register. Participants completed a self-administered questionnaire providing information on vaccination status, and sociodemographic and other factors.ResultsOverall, 880 (77%) women reported receiving ≥1 dose of the vaccine and 777 women (68%) reported receiving ≥2 doses. In multivariable analysis (adjusting for the period for which each woman was eligible for free HPV vaccination), uptake of ≥1 dose of the vaccine was significantly associated with being born in Australia (p < 0.01), being single (p = 0.02), being nulliparous (p < 0.01), living in a higher socioeconomic status area (p-trend = 0.03), living in more remote areas (p = 0.03), drinking alcohol (p < 0.01) and using hormonal contraceptives (p < 0.01). Although vaccinated women were more likely to have fewer sexual partners than unvaccinated women (p-trend = 0.02), they were also more likely to report a prior sexually transmitted infection (STI) (p = 0.03). Similar factors were associated with receiving ≥2 doses.ConclusionsIn this group, women living in higher socioeconomic status areas were more likely to be vaccinated against HPV in the catch-up phase of the national program. Although vaccinated women tended to have fewer sexual partners, they also reported prior STIs, which may be a marker of increased risk of prior exposure to HPV. The findings of this study reinforce the continuing need to prioritise equitable delivery of vaccination to various population subgroups.     

What predicts postpartum pertussis booster vaccination? A controlled intervention trial

Background‘Cocooning’ aims to protect susceptible infants from pertussis via caregiver vaccination. Control trials evaluating educational interventions to promote cocooning are lacking. We evaluated the role of message-framing vs. standard health information in promoting pertussis vaccination.MethodsWe recruited postpartum women from a maternity hospital in Sydney, Australia (November 2010–July 2012). Participants self-completed a pertussis knowledge and attitudes questionnaire. We then assigned pertussis-susceptible (no pertussis vaccine ≤10 years) participants to receive a gain-framed, loss-framed pamphlet or control (Government Pertussis factsheet) using weekly sequential block allocation. Next, participants were offered a pertussis vaccine (dTpa) and completed a post-questionnaire on discharge.ResultsA baseline questionnaire was completed for 96.4% (1433/1486) of postpartum women approached. Missing data was excluded (n = 29). Next, participants (1404) were screened for vaccine status: 324 (23%) reported prior pertussis booster vaccine receipt, leaving 1080 participants requiring vaccination. Among susceptible mothers, 70% (754/1080) were vaccinated post-intervention. Rates were similar between ‘gain’, ‘loss’ or ‘control’ pamphlets (69.1% vs. 71.8% vs. 68.8%; p = 0.62). Intention to be vaccinated (OR 2.46, p < 0.001; 95% CI: 1.69–3.58), perceived vaccine benefits (OR: 1.61, p < 0.001; 95% CI: 1.25–2.15) and having received a vaccine recommendation (OR 1.68; p = 0.025; 95% CI: 1.07–2.65) were independent predictors of vaccine uptake. At discharge, overall pertussis vaccine coverage had increased from 23% to 77% among women screened (1078/1404).ConclusionA cocooning strategy for pertussis vaccination can be highly effective when partially implemented within maternity hospitals, with information accompanied by a funded vaccine. Mothers were highly receptive to vaccination in the postnatal ward: facts about pertussis were as effective as message-framing in promoting a high uptake of 70%. Perceived vaccine benefits, intentions and vaccine recommendation were important predictors of uptake. Our intervention trial increased the existing pertussis vaccine coverage of 23–77%.     

A case for preART-adjusted endpoints in HIV therapeutic vaccine trials

BackgroundIn a randomized, double-blind, placebo-controlled phase 2 clinical trial of Vacc-4x, a peptide-based therapeutic HIV-1 p24^Gag vaccine candidate, 135 HIV-infected participants (vaccine:placebo = 92:43) received a series of six immunizations while on combination antiretroviral therapy (cART). At week 28, all participants underwent an analytical treatment interruption (ATI) for up to 24 weeks. preART VL appeared to be higher among Vacc-4x recipients. Based on a previous analysis, during ATI viral load (VL) appeared to be lower in Vacc-4x recipients, but no difference in CD4 level was observed between Vacc-4x and placebo groups. We propose fold-change-based endpoints and report comparative analyses accounting for imbalanced preART VL and missing data.MethodsAll analyses included per-protocol (PP) participants who received the full immunization and underwent ATI. Linear regression models were used to identify predictors of study endpoints and to estimate the vaccine effect based on fold changes in CD4 counts or VL over preART values at week 40 or at set-point (geometric mean over weeks 48 and 52 values). We adjusted for potential baseline factors and used a multiple imputation approach to account for missing endpoints due to cART resumption or dropout. P-values were adjusted for multiple comparisons using q-values.ResultspreART VL and CD4 count were significant predictors of study endpoints. The vaccine recipients had a higher fold change in week 40 CD4 counts (vaccine vs. placebo mean fold-change difference = 0.08; p = 0.02; q = 0.03), a higher fold change in CD4 count set-point (0.06; p = 0.06; q = 0.07), a lower fold change in week 40 VL (−0.47; p = 0.03; q = 0.05), and a lower fold change in VL set-point (−0.50; p = 0.02; q = 0.03).ConclusionsThese exploratory analyses consistently suggested that Vacc-4x provided positive effects on both CD4 counts and VL. Future HIV therapeutic vaccine studies may adopt similar preART-adjusted endpoints and missing data imputation methods in vaccine effect evaluations.     

Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection

BackgroundCongenital cytomegalovirus infection can be life-threatening and often results in significant developmental deficits and/or hearing loss. Thus, there is a critical need for an effective anti-CMV vaccine.ObjectiveTo determine the efficacy of replication-defective lymphocytic choriomeningitis virus (rLCMV) vectors expressing the guinea pig CMV (GPCMV) antigens, gB and pp65, in the guinea pig model of congenital CMV infection.MethodsFemale Hartley strain guinea pigs were divided into three groups: Buffer control group (n = 9), rLCMV-gB group (n = 11), and rLCMV-pp65 (n = 11). The vaccines were administered three times IM at 1.54 × 10⁶ FFU per dose at 21-day intervals. At two weeks after vaccination, the female guinea pigs underwent breeding. Pregnant guinea pigs were challenged SQ at ∼45–55 days of gestation with 1 × 10⁵ PFU of GPCMV. Viremia in the dams, pup survival, weights of pups at delivery, and viral load in both dam and pup tissues were determined.ResultsPup survival was significantly increased in the LCMV-gB vaccine group. There was 23% pup mortality in the gB vaccine group (p = 0.044) and 26% pup mortality in the pp65 vaccine group (p = 0.054) compared to 49% control pup mortality. The gB vaccine induced high levels of gB binding and detectable neutralizing antibodies, reduced dam viremia, and significantly reduced viral load in dam tissues compared to control dams (p < 0.03). Reduced viral load and transmission in pups born to gB-vaccinated dams was observed compared to pups from pp65-vaccinated or control dams.ConclusionsThe rLCMV-gB vaccine significantly improved pup survival and also increased pup weights and gestation time. The gB vaccine was also more effective at decreasing viral load in dams and pups and limiting congenital transmission. Thus, rLCMV vectors that express CMV antigens may be an effective vaccine strategy for congenital CMV infection.     

Comparative immunogenicity of hepatitis B vaccine with different dosages and schedules in healthy young adults in China

ObjectivesTo compare immunogenicity of hepatitis B vaccine between the standard 3-dose (20 μg) and 2-dose with higher-dosage (60 μg) regimens in healthy young adults and evaluate the safety profile.MethodsA randomized, parallel-group clinical trial was conducted among healthy young adults aged 18−25 years. Subjects were randomly assigned to three groups. One group was administered hepatitis B vaccine with the standard regimen of 0−1−6 month (20 μg) and other groups were immunized with regimens of 0−1 or 0−2 month (60 μg) respectively. Serum samples were collected at 1 month after a series vaccination and 12 months after the first-dose inoculation for anti-HBs antibody measurement with a Chemiluminescent Microparticle ImmunoAssay (CMIA).ResultsThe seroprotection rates in 20 μg (0−1−6 month), 60 μg (0−1 month) and 60 μg (0−2 month) groups were 100, 93.64 and 99.19% at month 7/2/3, and 100, 96.04 and 95.90% at month 12, respectively. There were no significant differences among three vaccine groups (p > 0.05). The geometric mean concentration (GMC) of anti-HBs was significantly higher in 20 μg (0−1−6 month) group than that in 60 μg (0−1 month) group at month 7/2 (1847.99 vs. 839.27 mIU/ml, p = 0.004), but was similar to that in 60 μg (0−2 month) group at month 7/3 (1847.99 vs. 1244.80 mIU/ml, p = 0.138). At month 12, the GMC in 20 μg (0−1−6 month) group was significantly higher than those of other groups (1456.63 vs. 256.30, 235.15 mIU/ml, respectively, p < 0.001). The total incidence of injection-site or systemic adverse reactions was <3%.ConclusionsA 2-dose with higher-dosage hepatitis B vaccine regimens are comparable to the standard 3-dose regimen in terms of immunogenicity except a relatively rapid decline in GMC levels which are associated with the longevity of protection. All formulations of hepatitis B vaccine were well tolerated.Clinicaltrials.gov identifierNCT02203357.     

Impact of the 13-valent pneumococcal conjugate vaccine on Streptococcus pneumoniae multiple serotype carriage

IntroductionPneumococcal multiple serotype carriage is important for evolution of the species and to understand how the pneumococcal population is changing with vaccination. We aimed to determine the impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on multiple serotype carriage.Methods and materialsNasopharyngeal samples from fully vaccinated pneumococcal carriers (4 doses of PCV13, n = 141, aged 18–72 months) or from non-vaccinated pneumococcal carriers (0 doses of any PCV, n = 140, same age group) were analyzed. Multiple serotype carriage was evaluated by DNA hybridization with a molecular serotyping microarray that detects all known serotypes.ResultsVaccinated children had a lower prevalence of multiple serotype carriage than the non-vaccinated group (20.6% vs 29.3%, p = 0.097), and a significantly lower proportion of PCV13 serotypes (6.4% vs 38.5%, p = 0.0001). PCV13 serotypes found among vaccinated children were mostly detected as a minor serotype in co-colonization with a more abundant non-vaccine serotype. Vaccinated children were colonized by a significantly higher proportion of commensal non-pneumococcal Streptococcus spp. (58.2% vs 42.8%, p = 0.012). In vaccinated children there were significantly less non-vaccine type (NVT) co-colonization events than expected based on the distribution of these serotypes in non-vaccinated children.ConclusionsThe results suggest that vaccinated children have lower pneumococcal multiple serotype carriage prevalence due to higher competitive abilities of non-vaccine serotypes expanding after PCV13 use. This might represent an additional benefit of PCV13, as decreased co-colonization rates translate into decreased opportunities for horizontal gene transfer and might have implications for the evolution and virulence of pneumococci.     

Pertussis vaccination during pregnancy in Belgium: Follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age

Vaccination of pregnant women with a pertussis containing vaccine is a recommended strategy in some industrialized countries, to protect young infants from severe disease. One of the effects of the presence of high titers of passively acquired maternal antibodies in young infants is blunting of immune responses to infant vaccination. We present infant immune responses to a fourth pertussis containing vaccine dose at 15 months of age, as a follow-up of previously presented data.In a prospective cohort study, women were either vaccinated with an acellular pertussis vaccine (Boostrix^®) during pregnancy (vaccine group) or received no vaccine (control group).All infants were vaccinated with Infanrix Hexa^® according to the standard Belgian vaccination schedule (8/12/16 weeks, 15 months). We report results from blood samples collected before and 1 month after the fourth vaccine dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT) and diphtheria toxoid (DT) were measured using commercially available ELISA tests. Antibody levels were expressed in International Units per milliliter.Demographic characteristics were similar in the vaccine and control group. Before the fourth vaccine dose, significantly lower antibody titers were measured in the vaccine group compared to the control group for anti-Prn IgG (p = 0.003) and anti-DT IgG (p = 0.023), with a steep decay of antibody titers since post-primary vaccination. One month after the fourth dose, antibody titers were only significantly lower in the vaccine group for anti-PT IgG (p = 0.006). For all antigens, there was a rise in antibody titer after the fourth vaccine dose.The present results indicate still a minor blunting effect 1 month after a fourth vaccine dose for anti-PT antibodies. However, a good humoral immune response on all measured antigens was elicited in both groups of children. The clinical significance of such blunting effect is yet unknown.Clinicaltrials.gov identifier: NCT01698346.     

Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts,restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection

BackgroundThis randomised, open label, phase I, immunotherapeutic study investigated the effects of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human growth hormone (rhGH), and therapeutic immunisation (a Clade B DNA vaccine) on combination antiretroviral therapy (cART)-treated HIV-1-infected individuals, with the objective to reverse residual T-cell dysfunction.MethodsTwelve HIV-1⁺ patients on suppressive cART with baseline CD4 T-cell counts >400 cells/mm³ blood were randomised into one of three groups: (1) vaccine, IL-2, GM-CSF and rhGH (n = 3); (2) vaccine alone (n = 4); or (3) IL-2, GM-CSF and rhGH (n = 5). Samples were collected at weeks 0, 1, 2, 4, 6, 8, 12, 16, 24 and 48. Interferon (IFN)-γ, IL-2, IL-4 and perforin ELISpot assays performed at each time point quantified functional responses to Gag p17/p24, Nef, Rev, and Tat peptides; and detailed T-cell immunophenotyping was undertaken by flow cytometry. Proviral DNA was also measured.ResultsMedian baseline CD4 T-cell count was 757 cells/mm³ (interquartile range [IQR] 567–886 cells/mm³), median age 48 years (IQR 42–51 years), and plasma HIV-1-RNA <50 copies/ml for all subjects. Patients who received vaccine plus IL-2, GM-CSF and rhGH (group 1) showed the most marked changes. Assessing mean changes from baseline to week 48 revealed significantly elevated numbers of CD4 T cells (p = 0.0083) and improved CD4/CD8 T-cell ratios (p = 0.0033). This was accompanied by a significant reduction in expression of CD38 on CD4 T cells (p = 0.0194), significantly increased IFN-γ and IL-2 production in response to Gag (p = 0.0122) and elevated IFN-γ production in response to Tat (p = 0.041) at week 48 compared to baseline. Subjects in all treatment groups showed significantly reduced PD-1 expression at week 48 compared to baseline, with some reductions in proviral DNA.ConclusionsMultifarious immunotherapeutic approaches in the context of fully suppressive cART further reduce immune activation, and improve both CD4 T-lymphocyte counts and HIV-1-specific T-cell responses (NCT01130376).     

Promoting Tdap immunization in pregnancy: Associations between maternal perceptions and vaccination rates

ObjectiveTdap vaccine uptake among US pregnant women is low despite current recommendations. This study evaluated if a Tdap vaccine information statement (VIS) affected overall perception, vaccination intention, and components of a health behavior model associated with Tdap vaccination rates.MethodsA randomized, prospective study was conducted among pregnant women receiving care at two women's clinics in May–August 2014. Verbally consented participants were randomized to receive either the standard CDC Tdap VIS (sVIS) or a modified version (mVIS) before completing the first multi-part survey (T1). After T1, participants read their assigned VIS then completed the second part (T2). A 2015 chart review identified vaccinated participants. A health behavior model was hypothesized using the Reasoned Action Approach and Health Belief Model. Logistic regression, path analysis, and chi-square tests were used in the analysis.Results279 surveys were analyzed. Average age of the participants was 26.4 years (SD = 5.7) with average gestational age of 25.9 weeks (SD = 9.2). 13% self-reported receiving Tdap vaccine prior to the survey. Overall perception scores significantly increased (3.1–3.4, p < 0.001) after VIS review. A chart review showed that 131 (47%) received the vaccine post study. There was no significant difference in vaccination rates between the sVIS and mVIS groups (45% vs. 49%). Perceived benefits (B = 0.315) and self-efficacy (B = 0.197) were positively associated with the overall perception (T1), while perceived barriers (B = −0.191) were negatively associated with the overall perception (T1). Social norms (B = 0.230), self-efficacy (B = 0.213), and perceived benefits (B = 0.117) were positively associated with vaccination intention (T1). The vaccination intention (T2) was positively associated with participants’ decision to receive Tdap vaccine (B = 0.223).ConclusionA VIS improved overall perception of the Tdap vaccine. Vaccination intention was a predictor of Tdap vaccination. It is crucial to provide information about immunization benefits to promote maternal Tdap vaccination.     

The effect of P2X7 receptor 1513 polymorphism on susceptibility to tuberculosis: A meta-analysis

Studies of the association between the purinergic receptor P2X, ligand-gated ion channel 7 (P2X7 receptor) gene 1513A/C polymorphism and susceptibility to tuberculosis have yielded inconsistent results. We performed this meta-analysis to help clarify these inconsistencies. After systematically searching PUBMED, MEDLINE, EMBASE and ISI Web of knowledge, two of the authors independently extracted relevant data and a meta-analysis was performed by using STATA11.0 software. A total number of nine studies involving 2195 cases and 2036 controls were identified. The results indicated that P2X7 receptor gene 1513C allele (OR 1.389, 95% CI 1.161–1.660, p < 0.001) and CC genotype (1.582, 95% CI 1.129–2.217, p = 0. 012) were significantly associated with increased susceptibility to tuberculosis. Subgroup analysis indicated that this SNP greatly contributed to susceptibility to tuberculosis in Asians. The C allele of P2X7 receptor gene 1513A/C polymorphism was also associated with increased susceptibility to pulmonary tuberculosis in Asians (C vs. A: OR 1.420, 95% CI 1.163–1.733, p = 0.001; (CC + AC) vs. AA: OR 1.522, 95% CI 1.186–1.953, p = 0.001). Greater association between P2X7 receptor gene 1513A/C polymorphism and susceptibility to extra-pulmonary tuberculosis with bigger ORs were found (C vs. A, OR 2.035, 95% CI 1.236–3.352, p = 0.005; CC vs. AA, OR 3.788, 95% CI 1.434–10.009, p = 0.007; AC vs. AA, OR 2.148, 95% CI 1.252–3.684, p = 0.005; (CC + AC) vs. AA, OR 2.386, 95% CI 1.302–4.374, p = 0.005; CC vs. (AC + AA), OR 2.692, 95% CI 1.242–5.836, p = 0. 012). This meta-analysis indicates that the C allele of P2X7 receptor gene 1513A/C polymorphism is a risk factor for pulmonary tuberculosis in Asians, while not in Africans or Latinos and a risk for extra-pulmonary tuberculosis. Further well-designed, large scale studies are required to confirm this conclusion.     

Breastfeeding linked to the reduction of both rotavirus shedding and IgA levels after Rotarix® immunization in Mexican infants

We examined potential risk factors on vaccine virus shedding and antibody seroresponse to human rotavirus vaccine (Rotarix) in Mexican infants. Two doses of Rotarix were administered to infants during the first two visits for their routine childhood immunization (∼8 and 15 weeks of age) in Mexico City. Infant’s characteristics and socioeconomic indicators were obtained, including history of long-term feeding practices (exclusively/predominantly breastfed and exclusively/predominantly non-breastfed). Two serum specimens were collected, one during the second rotavirus vaccine visit and one 7 weeks later. Stool specimens were collected between days 4–7 after each of the two rotavirus vaccine doses. Rotavirus IgA and IgG titers in serum were determined by enzyme immunoassays (EIA) and rotavirus shedding in stool was assessed by EIA and confirmed by RT-PCR.The overall rotavirus IgA geometric mean titers (GMT) increased significantly post dose 2 from post dose 1 [176 (95%CI: 113–273) to 335 (238–471); p = 0.020). Infants who were exclusively/predominantly breastfed were less likely to shed vaccine virus in stool than those who were formula-fed (22% vs. 43%, p = 0.016). Infants who were breastfed had lower rotavirus IgA titers than those who were formula-fed after dose 1 [GMT: 145 (84–250) vs. 267 (126–566) p = 0.188] and dose 2 [236 (147–378) vs.578 (367–910), p = 0.007]. Infants who shed vaccine virus post dose 1 had significantly higher serum IgA GMT than those who did not shed [425 (188–965) vs. 150 (84–266), p = 0.038]. Breastfeeding was linked with the reduction of both stool vaccine shedding, and IgA seroresponse. The reduced rotavirus replication in the gut and shedding after dose 1 may explain in part the lower IgA response in serum.     

A global review of national influenza immunization policies: Analysis of the 2014 WHO/UNICEF Joint Reporting Form on immunization

IntroductionThe WHO recommends annual influenza vaccination to prevent influenza illness in high-risk groups. Little is known about national influenza immunization policies globally.Material and MethodsThe 2014 WHO/UNICEF Joint Reporting Form (JRF) on Immunization was adapted to capture data on influenza immunization policies. We combined this dataset with additional JRF information on new vaccine introductions and strength of immunization programmes, as well as publicly available data on country economic status. Data from countries that did not complete the JRF were sought through additional sources. We described data on country influenza immunization policies and used bivariate analyses to identify factors associated with having such policies.ResultsOf 194 WHO Member States, 115 (59%) reported having a national influenza immunization policy in 2014. Among countries with a national policy, programmes target specific WHO-defined risk groups, including pregnant women (42%), young children (28%), adults with chronic illnesses (46%), the elderly (45%), and health care workers (47%). The Americas, Europe, and Western Pacific were the WHO regions that had the highest percentages of countries reporting that they had national influenza immunization policies. Compared to countries without policies, countries with policies were significantly more likely to have the following characteristics: to be high or upper middle income (p < 0.0001); to have introduced birth dose hepatitis B virus vaccine (p < 0.0001), pneumococcal conjugate vaccine (p = 0.032), or human papilloma virus vaccine (p = 0.002); to have achieved global goals for diphtheria-tetanus-pertussis vaccine coverage (p < 0.0001); and to have a functioning National Immunization Technical Advisory Group (p < 0.0001).ConclusionsThe 2014 revision of the JRF permitted a global assessment of national influenza immunization policies. The 59% of countries reporting that they had policies are wealthier, use more new or under-utilized vaccines, and have stronger immunization systems. Addressing disparities in public health resources and strengthening immunization systems may facilitate influenza vaccine introduction and use.