Evaluation of Three Vaccine Technologies to Protect White leghorn Chickens from H5N2 clade 2.3.4.4 Gs/GD High Pathogenicity Avian Influenza

USDA-ARS?s Scientific Manuscript database

During December 2014-June 2015, the USA experienced a high pathogenicity avian influenza (HPAI) outbreak caused by clade 2.3.4.4 H5Nx Goose/Guangdong lineage viruses which was the worst HPAI event for the USA’s poultry industries. Three emergency vaccines, based on updating existing registered vacc...

Altered Neural Processing to Social Exclusion in Young Adult Marijuana Users

PubMed Central

Gilman, Jodi M.; Curran, Max T.; Calderon, Vanessa; Schuster, Randi M.; Evins, A. Eden

2015-01-01

Previous studies have reported that peer groups are one of the most important predictors of adolescent and young adult marijuana use, and yet the neural correlates of social processing in marijuana users have not yet been studied. In the current study, marijuana-using young adults (n = 20) and non-using controls (n = 22) participated in a neuroimaging social exclusion task called Cyberball, a computerized ball-tossing game in which the participant is excluded from the game after a pre-determined number of ball tosses. Controls, but not marijuana users, demonstrated significant activation in the insula, a region associated with negative emotion, when being excluded from the game. Both groups demonstrated activation of the ventral anterior cingulate cortex (vACC), a region associated with affective monitoring, during peer exclusion. Only the marijuana group showed a correlation between vACC activation and scores on a self-report measure of peer conformity. This study indicates that marijuana users show atypical neural processing of social exclusion, which may be either caused by, or the result of, regular marijuana use. PMID:26977454

ADVERSE EVENTS POST-DTAP AND DTwP VACCINATION IN THAI CHILDREN.

PubMed

Fortuna, Librada; Sirivichayakul, Chukiat; Watanaveeradej, Veerachai; Soonthornworasiri, Ngamphol; Sitcharungsi, Raweerat

2015-07-01

We conducted a prospective study to compare the development of fever (axillary T ≥ 37.9 °C) within 4 hours of vaccination, determine the proportion of children who develop high fever (T ≥ 39°C) and evaluate parental days missed from work due to their children's vaccination with either the diphtheria-tetanus-whole cell pertussis (DTwP) or diphtheria-tetanus-acellular pertussis (DTaP) vaccine. The results of this study can help physicians and parents decide whether to have their child vaccinated with the DTwP or more expensive DTaP vaccine. We studied 140 healthy Thai children aged 2 months to 6 years from December 2011 to March 2012 who presented for vaccination. Parents recorded their child's temperature, local and systemic adverse reactions and missed days from work due to these adverse events on a diary card. Of the 140 participants, 72 received the DTwP vaccine and 68 received the DTaP vaccine. The median (IQR) age was 4 (2-6) months and the median weight was 7.1 (5.6-8.7) kg. Twenty children developed fever (axillary T ≥ 37.9°C) within 4 hours following vaccination, 17 (23.6%) had received the DTwP vaccine and 3 (4.4%) had received the DTaP vaccine (p = 0.040). One child (1.4%) who had received the DTwP vaccine and none who received the DTaP vaccine developed high fever (T ≥ 39°C) within 4 hours of vaccination (p = 0.329). Parents of two children who received the DTwP vaccine and one child who received the DTaP vaccine missed work following vaccination (p = 0.059). In conclusion, children who received the DTwP vaccines were more likely to have early post-vaccination fever and higher fever but there was no significant difference between the two groups in parental days lost from work.

IgE sensitization to gelatin: the probable role of gelatin-containing diphtheria-tetanus-acellular pertussis (DTaP) vaccines.

PubMed

Sakaguchi, M; Inouye, S

2000-04-03

We recently found that most events of anaphylaxis to live attenuated viral vaccines containing gelatin as a stabilizer might be caused by the gelatin. However, the mechanism that the children were sensitized to gelatin was unclear. In Japan, both diphtheria-tetanus-acellular pertussis (DTaP) vaccines with and without gelatin are available. We explored the possibility that gelatin-containing DTaP vaccines before live viral vaccines sensitize children to gelatin. We received the serum samples of 87 children who had systemic immediate-type reactions including anaphylaxis to the vaccines from both physicians and vaccine manufacturers throughout Japan. We then surveyed the DTaP vaccination histories of the children who demonstrated anti-gelatin IgE. Of the above 87 children, 79 (91%) had anti-gelatin IgE. We successfully collected DTaP vaccination histories including the manufacturers' names and numbers of doses on 55 children. Only one child had not received any DTaP vaccine, the other 54 had received gelatin-containing DTaP vaccines and none received gelatin-free DTaP vaccines. We concluded that there was a strong causal relationship between gelatin-containing DTaP vaccination, anti-gelatin IgE production, and risk of anaphylaxis following subsequent immunization with live viral vaccines which contain a larger amount of gelatin.

Incomplete Early Childhood Immunization Series and Missing Fourth DTaP Immunizations; Missed Opportunities or Missed Visits?

PubMed

Robison, Steve G

2013-01-01

The successful completion of early childhood immunizations is a proxy for overall quality of early care. Immunization statuses are usually assessed by up-to-date (UTD) rates covering combined series of different immunizations. However, series UTD rates often only bear on which single immunization is missing, rather than the success of all immunizations. In the US, most series UTD rates are limited by missing fourth DTaP-containing immunizations (diphtheria/tetanus/pertussis) due at 15 to 18 months of age. Missing 4th DTaP immunizations are associated either with a lack of visits at 15 to 18 months of age, or to visits without immunizations. Typical immunization data however cannot distinguish between these two reasons. This study compared immunization records from the Oregon ALERT IIS with medical encounter records for two-year olds in the Oregon Health Plan. Among those with 3 valid DTaPs by 9 months of age, 31.6% failed to receive a timely 4th DTaP; of those without a 4th DTaP, 42.1% did not have any provider visits from 15 through 18 months of age, while 57.9% had at least one provider visit. Those with a 4th DTaP averaged 2.45 encounters, while those with encounters but without 4th DTaPs averaged 2.23 encounters.

Immune interaction between components of acellular pertussis-diphtheria-tetanus (DTaP) vaccine and Haemophilus influenzae b (Hib) conjugate vaccine in a rat model.

PubMed

Mawas, Fatme; Dickinson, Robert; Douglas-Bardsley, Alexandra; Xing, Dorothy K L; Sesardic, Dorothea; Corbel, Michael J

2006-04-24

We have previously shown that, consistent with clinical trial results, the immune response to a Haemophilus influenzae b (Hib) conjugate vaccine in a rat model was compromised and modulated when given combined with a DTaP3 vaccine, as compared to both vaccines given separately. The present study extended our investigation to evaluate the immunogenicity of all DTaP3 components in combined versus separate administration of Hib with DTaP3 and investigated immune interactions between Hib and individual components of DTaP3. Rats were immunised with Hib and DTaP3 or with Hib and individual DTaP3 components. Cellular and humoral immune responses to Hib and DTaP3 components were evaluated. Our results indicate that the immunogenicity of DTaP3 components was similar or greater in combined versus separate administration of Hib and DTaP3. Moreover, combined administration of Hib and TT reduced immunogenicity of both Hib and TT. Hib immunogenicity was also significantly reduced when given combined with FHA and following adsorption to Al(OH)3.

Association between Genetic Polymorphisms in Cav2.3 (R-type) Ca2+ Channels and Fentanyl Sensitivity in Patients Undergoing Painful Cosmetic Surgery

PubMed Central

Fukuda, Ken-ichi; Kasai, Shinya; Hasegawa, Junko; Hayashida, Masakazu; Minami, Masabumi; Ikeda, Kazutaka

2013-01-01

Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, lead to different proper doses of fentanyl, which can hamper effective pain treatment. Voltage-activated Ca2+ channels (VACCs) play a crucial role in the nervous system by controlling membrane excitability and calcium signaling. Cav2.3 (R-type) VACCs have been especially thought to play critical roles in pain pathways and the analgesic effects of opioids. However, unknown is whether single-nucleotide polymorphisms (SNPs) of the human CACNA1E (calcium channel, voltage-dependent, R type, alpha 1E subunit) gene that encodes Cav2.3 VACCs influence the analgesic effects of opioids. Thus, the present study examined associations between fentanyl sensitivity and SNPs in the human CACNA1E gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. We first conducted linkage disequilibrium (LD) analyses of 223 SNPs in a region that contains the CACNA1E gene using genomic samples from 100 patients, and a total of 13 LD blocks with 42 Tag SNPs were observed within and around the CACNA1E gene region. In the preliminary study using the same 100 genomic samples, only the rs3845446 A/G SNP was significantly associated with perioperative fentanyl use among these 42 Tag SNPs. In a confirmatory study using the other 255 genomic samples, this SNP was also significantly associated with perioperative fentanyl use. Thus, we further analyzed associations between genotypes of this SNP and all of the clinical data using a total of 355 samples. The rs3845446 A/G SNP was associated with intraoperative fentanyl use, 24 h postoperative fentanyl requirements, and perioperative fentanyl use. Subjects who carried the minor G allele required significantly less fentanyl for pain control compared with subjects who did not carry this allele. Although further validation is needed, the present findings show the possibility of the involvement of CACNA1E gene polymorphisms

Gelatin-specific cellular immune responses persist for more than 3 years after priming with gelatin containing DTaP vaccine.

PubMed

Kumagai, T; Kamada, M; Igarashi, C; Yuri, K; Furukawa, H; Nagata, N; Saito, A; Okui, T; Yano, S

2002-10-01

Gelatin-specific cell-mediated immunity develops in subjects inoculated with gelatin containing DTaP vaccine. However, it is not yet known whether such established sensitization to gelatin disappears or persists with time. The aim of this study was to follow the patients with gelatin sensitization elicited by DTaP vaccination for their lymphocyte responsiveness and IgE, IgG antibody specific to gelatin over several years and to compare the activities with those at the time of enrollment into the study. We studied 28 subjects who developed positive lymphocyte proliferation test (LPT) after receiving gelatin containing DTaP vaccine and eight subjects who had a negative LPT after inoculation of non-gelatin DTaP. Determination of IgE, IgG antibodies and specific lymphoproliferative response directed against gelatin were performed at enrollment and on follow up. None of the subjects had antibody to gelatin at enrollment and none developed gelatin IgE or IgG during follow-up. There was no significant difference in the SIs of the subjects receiving gelatin DTaP (P = 0.150, 95% CI, -0.198-0.032), whereas lymphocyte activity to gelatin increased between enrollment and follow-up in the subjects with non-gelatin DTaP (P = 0.011, 95% CI, 0.063-0.338). Gelatin-specific lymphocyte activity persists at comparable levels for more than 3 years in subjects who acquire a positive LPT response to gelatin after receiving primary DTaP vaccine containing gelatin. Furthermore, five out of eight subjects initially with negative LPT to gelatin have been shown to acquire specific LPT with time.

Load-related brain activation predicts spatial working memory performance in youth aged 9–12 and is associated with executive function at earlier ages

PubMed Central

Huang, Anna S.; Klein, Daniel N.; Leung, Hoi-Chung

2015-01-01

Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9–12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal-parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders. PMID:26562059

Neural correlates of appetitive extinction in humans.

PubMed

Kruse, Onno; Tapia León, Isabell; Stark, Rudolf; Klucken, Tim

2017-01-01

Appetitive extinction receives attention as an important model for the treatment of psychiatric disorders. However, in humans, its underlying neural correlates remain unknown. To close this gap, we investigated appetitive acquisition and extinction with fMRI in a 2-day monetary incentive delay paradigm. During appetitive conditioning, one stimulus (CS+) was paired with monetary reward, while another stimulus (CS-) was never rewarded. Twenty-four hours later, subjects underwent extinction, in which neither CS was reinforced. Appetitive conditioning elicited stronger skin conductance responses to the CS+ as compared with the CS-. Regarding subjective ratings, the CS+ was rated more pleasant and arousing than the CS- after conditioning. Furthermore, fMRI-results (CS+ - CS-) showed activation of the reward circuitry including amygdala, midbrain and striatal areas. During extinction, conditioned responses were successfully extinguished. In the early phase of extinction, we found a significant activation of the caudate, the hippocampus, the dorsal and ventral anterior cingulate cortex (dACC and vACC). In the late phase, we found significant activation of the nucleus accumbens (NAcc) and the amygdala. Correlational analyses with subjective ratings linked extinction success to the vACC and the NAcc, while associating the dACC with reduced extinction. The results reveal neural correlates of appetitive extinction in humans and extend assumptions from models for human extinction learning. © The Author (2016). Published by Oxford University Press.

Load-related brain activation predicts spatial working memory performance in youth aged 9-12 and is associated with executive function at earlier ages.

PubMed

Huang, Anna S; Klein, Daniel N; Leung, Hoi-Chung

2016-02-01

Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9-12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal-parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neural correlates of appetitive extinction in humans

PubMed Central

Tapia León, Isabell; Stark, Rudolf; Klucken, Tim

2017-01-01

Abstract Appetitive extinction receives attention as an important model for the treatment of psychiatric disorders. However, in humans, its underlying neural correlates remain unknown. To close this gap, we investigated appetitive acquisition and extinction with fMRI in a 2-day monetary incentive delay paradigm. During appetitive conditioning, one stimulus (CS+) was paired with monetary reward, while another stimulus (CS−) was never rewarded. Twenty-four hours later, subjects underwent extinction, in which neither CS was reinforced. Appetitive conditioning elicited stronger skin conductance responses to the CS+ as compared with the CS−. Regarding subjective ratings, the CS+ was rated more pleasant and arousing than the CS− after conditioning. Furthermore, fMRI-results (CS+ − CS−) showed activation of the reward circuitry including amygdala, midbrain and striatal areas. During extinction, conditioned responses were successfully extinguished. In the early phase of extinction, we found a significant activation of the caudate, the hippocampus, the dorsal and ventral anterior cingulate cortex (dACC and vACC). In the late phase, we found significant activation of the nucleus accumbens (NAcc) and the amygdala. Correlational analyses with subjective ratings linked extinction success to the vACC and the NAcc, while associating the dACC with reduced extinction. The results reveal neural correlates of appetitive extinction in humans and extend assumptions from models for human extinction learning. PMID:27803289

DTaP Vaccine (Diphtheria, Tetanus, and Pertussis): What You Need to Know

MedlinePlus

... time as other vaccines. 3 SDoTamPevcahcicldinreenosrhsohuoludldnowtagitet • Children with minor illnesses, such as a cold, may be vaccinated. ... age and older. But older people still need protection. A vaccine called Tdap is similar to DTaP. ...

A freeze-stable formulation for DTwP and DTaP vaccines.

PubMed

Xue, Honggang; Yang, Bangling; Kristensen, Debra D; Chen, Dexiang

2014-01-01

Inadvertent vaccine freezing often occurs in the cold chain and may cause damage to freeze‑sensitive vaccines. Liquid vaccines that contain aluminum salt adjuvants are particularly vulnerable. Polyol cryoprotective excipients have been shown to prevent freeze damage to hepatitis B vaccine. In this study, we examined the freeze-protective effect of propylene glycol on diphtheria-tetanus-pertussis-whole-cell (DTwP) and acellular (DTaP) vaccines. Pilot lots of DTwP and DTaP formulated with 7.5% propylene glycol underwent 3 freeze-thaw treatments. The addition of propylene glycol had no impact on pH, particle size distribution, or potency of the vaccines prior to freeze-thaw treatment; the only change noted was an increase in osmolality. The potencies and the physical properties of the vaccines containing cryoprotectant were maintained after freeze-thawing and for 3 months in accelerated stability studies. The results from this study indicate that formulating vaccines with propylene glycol can protect diphtheria-tetanus-pertussis vaccines against freeze damages.

Immunogenicity and safety of a new hexavalent vaccine (DTaP5-IPV-HB-Hib) administered in a mixed primary series schedule with a pentavalent vaccine (DTaP5-IPV-Hib).

PubMed

Martinón-Torres, Federico; Boisnard, Florence; Thomas, Stéphane; Sadorge, Christine; Borrow, Ray

2017-06-27

DTaP5-IPV-HB-Hib vaccine is a fully-liquid, combination hexavalent vaccine. This phase III, open-label, multicentre study conducted in Spain, evaluated the immune response to all DTaP5-IPV-HB-Hib antigens when the vaccine was used in a mixed hexa/penta/hexa primary series. Infants (who had received one dose of hepatitis B vaccine at birth) received a mixed schedule including DTaP5-IPV-HB-Hib (PRP-OMP conjugate) at 2 and 6months of age, DTaP5-IPV-Hib at 4months, meningococcal serogroup C conjugate (MCC) vaccine at 2 and 4months, and routine rotavirus and pneumococcal vaccination. One month post-dose 3 of the mixed schedule, response rates were considered acceptable if the lower bound of the two-sided 95% confidence interval around the post-vaccination response rate was >90% for hepatitis B and >80% for Haemophilus influenzae type b (Hib). Secondary immunogenicity objectives included description of the antibody response to all hexavalent antigens one month after completion of the mixed schedule, and to MCC antigen one month after the second MCC dose. The safety profile after each dose of study vaccine was described. Of 385 healthy infants enrolled, 384 completed the study. The primary objective was achieved for both hepatitis B and Hib; the lower bound of the 2-sided 95% CI of the response rates (97.2% and 99.0%, respectively) were greater than the pre-specified acceptability thresholds. One month post-dose 3 of the mixed schedule, all participants were seroprotected against diphtheria, tetanus and polio. The mixed schedule induced a robust immune response to all hexavalent antigens. The co-administration of the hexavalent vaccine in a mixed schedule with MCC vaccine did not reduce the immune response to vaccine antigens. Vaccines were well tolerated. In conclusion, the acceptability of response rates against Hib and hepatitis B were demonstrated one month post-dose 3 of the mixed schedule; robust immune responses against all other hexavalent antigens were observed

Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination.

PubMed

van der Lee, Saskia; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

2018-01-04

Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations. Blood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays. At 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children. The pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis. ISRCTN65428640; ISRCTN64117538; NTR4089. Copyright © 2017

Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens

PubMed Central

Asbach, Benedikt; Kliche, Alexander; Köstler, Josef; Perdiguero, Beatriz; Esteban, Mariano; Jacobs, Bertram L.; Montefiori, David C.; LaBranche, Celia C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; Roederer, Mario; Landucci, Gary; Forthal, Donald N.; Seaman, Michael S.; Hawkins, Natalie; Self, Steven G.; Sato, Alicia; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, James; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah E.; Francis, Jesse; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L.; Pantaleo, Giuseppe

2016-01-01

ABSTRACT In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8+ and CD4+ T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. IMPORTANCE Within the EuroVacc clinical trials, we previously assessed the immunogenicity of

Three Ways in Which Midline Regions Contribute to Self-Evaluation

PubMed Central

Flagan, Taru; Beer, Jennifer S.

2013-01-01

An integration of existing research and newly conducted psychophysiological interaction (PPI) connectivity analyses suggest a new framework for understanding the contribution of midline regions to social cognition. Recent meta-analyses suggest that there are no midline regions that are exclusively associated with self-processing. Whereas medial prefrontal cortex (MPFC) is broadly modulated by self-processing, subdivisions within MPFC are differentially modulated by the evaluation of close others (ventral MPFC: BA 10/32) and the evaluation of other social targets (dorsal MPFC: BA 9/32). The role of DMPFC in social cognition may also be less uniquely social than previously thought; it may be better characterized as a region that indexes certainty about evaluation rather than previously considered social mechanisms (i.e., correction of self-projection). VMPFC, a region often described as an important mediator of socioemotional significance, may instead perform a more cognitive role by reflecting the type of information brought to bear on evaluations of people we know well. Furthermore, the new framework moves beyond MPFC and hypothesizes that two other midline regions, ventral anterior cingulate cortex (VACC: BA 25) and medial orbitofrontal cortex (MOFC: BA 11), aid motivational influences on social cognition. Despite the central role of motivation in psychological models of self-perception, neural models have largely ignored the topic. Positive connectivity between VACC and MOFC may mediate bottom-up sensitivity to information based on its potential for helping us evaluate ourselves or others the way we want. As connectivity becomes more positive with striatum and less positive with middle frontal gyrus (BA 9/44), MOFC mediates top-down motivational influences by adjusting the standards we bring to bear on evaluations of ourselves and other people. PMID:23935580

Commercial PCV2a-based vaccines are effective in protecting naturally PCV2b-infected finisher pigs against experimental challenge with a 2012 mutant PCV2.

PubMed

Opriessnig, Tanja; Gerber, Priscilla F; Xiao, Chao-Ting; Halbur, Patrick G; Matzinger, Shannon R; Meng, Xiang-Jin

2014-07-23

Current commercial PCV2 vaccines are all based on PCV2a and have been shown to be effective in reducing PCV2a and PCV2b viremia and PCV2-associated lesions and disease. The recent emergence of novel mutant PCV2 (mPCV2) strains and linkage of mPCV2 with cases of porcine circovirus associated disease (PCVAD) in vaccinated herds have raised concerns over emergence of vaccine-escape mutants and reduced efficacy of PCV2a-based vaccines. The aim of this study was to determine the ability of three commercial PCV2a-based vaccines administered in the presence of an ongoing PCV2b infection and passively-acquired anti-PCV2 antibodies to protect conventional pigs against experimental challenge with mPCV2 at 11 weeks of age. Fifty naturally PCV2b-infected 2-week-old pigs were divided into five treatment groups with 10 pigs each. Pigs were unvaccinated (positive and negative controls) or vaccinated at 3 (VAC-A, VAC-B, VAC-C) and at 5 weeks of age (VAC-C). At 11 weeks of age, all pigs except the negative controls were challenged with a 2012 U.S. strain of mPCV2. The experiment was terminated 21 days after challenge. Under the conditions of this study, vaccinated pigs were protected against PCV2 viremia and lesions whereas non-vaccinated pigs were not. Moreover, concurrent PCV2b and mPCV2 infection was demonstrated in all positive controls and 3/10 had microscopic lesions consistent with PCVAD while negative controls infected with PCV2b alone did not develop PCVAD. The results indicate that concurrent PCV2b/mPCV2 infection can trigger PCVAD development and that commercial vaccines are effective in protecting conventional pigs against emerging mPCV2 strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

DTaP5-IPV-Hib-HepB, a hexavalent vaccine for infants and toddlers.

PubMed

Lee, Andrew W; Jordanov, Emilia; Boisnard, Florence; Marshall, Gary S

2017-02-01

Combination vaccines reduce the 'shot burden' and simplify the childhood immunization schedule. Only 5-valent DTaP-based vaccines are licensed in the U.S. Areas covered: A new combination vaccine - DTaP5-IPV-Hib-HepB - is described, which induces antibody responses in infants (given in different schedules, including a 2, 4, and 6-month schedule) that are similar to the respective component vaccines. The vaccine appears to be safe and would be expected to protect against six diseases: diphtheria, tetanus, pertussis, hepatitis B, H influenzae type b, and polio. Administration is associated with higher rates of mild fever, but without significant safety signals. Expert commentary: Incorporation of this hexavalent vaccine into the U.S. schedule could improve coverage rates and timeliness, and addition to the E.U. market would add depth to the available repertoire of combination vaccines.

Immunogenicity and safety of a combined DTaP-IPV vaccine compared with separate DTaP and IPV vaccines when administered as pre-school booster doses with a second dose of MMR vaccine to healthy children aged 4-6 years.

PubMed

Black, Steven; Friedland, Leonard R; Schuind, Anne; Howe, Barbara

2006-08-28

Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. A combined DTaP-IPV (Infanrix-IPV) vaccine has been developed for use as a pre-school booster. Four hundred healthy children aged 4-6 years previously primed with 4 doses of DTaP vaccine (Infanrix), 3 doses of poliovirus vaccine and 1 dose of MMR vaccine were randomized to receive single doses of either the combined DTaP-IPV vaccine or separate DTaP and IPV vaccines in a Phase II trial (DTaP-IPV-047). All children also received a second dose of MMR vaccine. Immunogenicity was assessed in serum samples taken before and 1 month after booster administration. Safety was actively assessed for 42 days post-vaccination. Non-inferiority of the DTaP-IPV vaccine to separate DTaP and IPV vaccines was demonstrated for all DTaP antigen booster response rates and poliovirus geometric mean titers of antibody ratios. Post-vaccination, > or =99.4% of children in both groups had seroprotective levels of anti-diphtheria and anti-tetanus antibodies (> or =0.1IU/mL) and seroprotective anti-poliovirus antibody titers (> or =1:8). All children in both groups were seropositive for measles, mumps and rubella antibodies, with similar post-vaccination geometric mean concentrations/titers. No significant differences were observed in the incidence of solicited local or general symptoms, unsolicited symptoms and serious adverse events between the two groups. This combined DTaP-IPV appeared safe and immunogenic when given as a booster dose at 4-6 years of age. The DTaP-IPV vaccine had no negative effect on the response to co-administered MMR vaccine, making it well-suited for use as a pre-school booster.

Transiently increased IgE responses in infants and pre-schoolers receiving only acellular Diphtheria-Pertussis-Tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellular vaccine (DTwP) - Immunological curiosity or canary in the mine?

PubMed

Holt, Patrick G; Snelling, Tom; White, Olivia J; Sly, Peter D; DeKlerk, Nicholas; Carapetis, Jonathan; Biggelaar, Anita Van Den; Wood, Nicholas; McIntyre, Peter; Gold, Michael

2016-07-29

Several previous studies have highlighted the strong Th2-polarising and IgE-promoting activity of the DTaP vaccine, but there is no evidence that this has pathological consequences and accordingly there is no current interest amongst vaccine developers in reformulating DTaP to attenuate these properties. In light of an apparent resurgence in pertussis in many countries, and emerging evidence from other areas of paediatric immunology of IgE-mediated interference with host defence mechanisms, this issue requires more detailed clarification. We have re-evaluated the impact of DTaP-only versus mixed DTwP/DTaP vaccination on Th2-dependent "bystander" IgE responses in three cohorts of children under different priming conditions, encompassing both vaccine-targeted and unrelated antigens including food allergens. We confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants. We additionally demonstrate that use of an alternative mixed infant priming schedule encompassing an initial dose of DTwP significantly attenuates this property. Central to our interpretation of these findings are studies demonstrating: (i) mixed DTwP/DTaP priming improves resistance to pertussis disease and attenuates the IgE-stimulatory component of long term vaccine-specific memory; (ii) IgE-mediated mechanisms can interfere with innate antiviral immunity and accordingly exacerbate airway symptoms in infected children. These observations, taken together with the data presented here, suggest a plausible mechanistic link between baseline pertussis-specific IgE titres in DTaP vaccinees and susceptibility to pertussis disease, which merits testing. Retrospective IgE analyses on sera collected from children at the time of presentation with pertussis could resolve this issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Predicting Stroop Effect from Spontaneous Neuronal Activity: A Study of Regional Homogeneity

PubMed Central

Liu, Congcong; Chen, Zhencai; Wang, Ting; Tang, Dandan; Hitchman, Glenn; Sun, Jiangzhou; Zhao, Xiaoyue; Wang, Lijun; Chen, Antao

2015-01-01

The Stroop effect is one of the most robust and well-studied phenomena in cognitive psychology and cognitive neuroscience. However, little is known about the relationship between intrinsic brain activity and the individual differences of this effect. In the present study, we explored this issue by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals could predict individual differences in the Stroop effect of healthy individuals. A partial correlation analysis was calculated to examine the relationship between regional homogeneity (ReHo) and Stroop effect size, while controlling for age, sex, and framewise displacement (FD). The results showed positive correlations in the left inferior frontal gyrus (LIFG), the left insula, the ventral anterior cingulate cortex (vACC), and the medial frontal gyrus (MFG), and negative correlation in the left precentral gyrus (LPG). These results indicate the possible influences of the LIFG, the left insula, and the LPG on the efficiency of cognitive control, and demonstrate that the key nodes of default mode network (DMN) may be important in goal-directed behavior and/or mental effort during cognitive control tasks. PMID:25938442

Altered reward learning and hippocampal connectivity following psychosocial stress.

PubMed

Kruse, Onno; Tapia León, Isabell; Stalder, Tobias; Stark, Rudolf; Klucken, Tim

2018-05-01

Acute stress has a profound influence on learning, as has been demonstrated in verbal learning or fear conditioning. However, its effect on appetitive conditioning is still unclear. Fear conditioning research suggests the possibility of overgeneralization of conditioning to the CS- under acute stress due to its effect on prefrontal and hippocampal processing. In this study, participants (N = 56 males) were subjected to the Trier Social Stress Test or a placebo version. After that, all participants underwent an appetitive conditioning paradigm in the fMRI, in which one neutral cue (CS+) was repeatedly paired with reward, while another (CS-) was not. Importantly, the stress-group revealed overgeneralization of conditioning to the CS- on the behavioral level. On the neural level, stressed participants showed increased connectivity between the hippocampus and amygdala, vACC, and OFC, which maintain specificity of conditioning and also showed reduced differential activation. The results indicate overgeneralization of appetitive conditioning promoted by maladaptive balancing of pattern separation and pattern completion in the hippocampus under acute stress and are discussed with respect to clinical implications. Copyright © 2017 Elsevier Inc. All rights reserved.

In vitro assembly of semi-artificial molecular machine and its use for detection of DNA damage.

PubMed

Minchew, Candace L; Didenko, Vladimir V

2012-01-11

Naturally occurring bio-molecular machines work in every living cell and display a variety of designs. Yet the development of artificial molecular machines centers on devices capable of directional motion, i.e. molecular motors, and on their scaled-down mechanical parts (wheels, axels, pendants etc). This imitates the macro-machines, even though the physical properties essential for these devices, such as inertia and momentum conservation, are not usable in the nanoworld environments. Alternative designs, which do not follow the mechanical macromachines schemes and use mechanisms developed in the evolution of biological molecules, can take advantage of the specific conditions of the nanoworld. Besides, adapting actual biological molecules for the purposes of nano-design reduces potential dangers the nanotechnology products may pose. Here we demonstrate the assembly and application of one such bio-enabled construct, a semi-artificial molecular device which combines a naturally-occurring molecular machine with artificial components. From the enzymology point of view, our construct is a designer fluorescent enzyme-substrate complex put together to perform a specific useful function. This assembly is by definition a molecular machine, as it contains one. Yet, its integration with the engineered part - fluorescent dual hairpin - re-directs it to a new task of labeling DNA damage. Our construct assembles out of a 32-mer DNA and an enzyme vaccinia topoisomerase I (VACC TOPO). The machine then uses its own material to fabricate two fluorescently labeled detector units (Figure 1). One of the units (green fluorescence) carries VACC TOPO covalently attached to its 3'end and another unit (red fluorescence) is a free hairpin with a terminal 3'OH. The units are short-lived and quickly reassemble back into the original construct, which subsequently recleaves. In the absence of DNA breaks these two units continuously separate and religate in a cyclic manner. In tissue sections

Spontaneous onset and transplant models of the Vk*MYC mouse show immunological sequelae comparable to human multiple myeloma.

PubMed

Cooke, Rachel E; Gherardin, Nicholas A; Harrison, Simon J; Quach, Hang; Godfrey, Dale I; Prince, Miles; Koldej, Rachel; Ritchie, David S

2016-09-06

The Vk*MYC transgenic and transplant mouse models of multiple myeloma (MM) are well established as a research tool for anti-myeloma drug discovery. However, little is known of the immune response in these models. Understanding the immunological relevance of these models is of increasing importance as immunotherapeutic drugs are developed against MM. We set out to examine how cellular immunity is affected in Vk*MYC mouse models and compare that to the immunology of patients with newly diagnosed and relapsed/refractory MM. We found that there were significant immunological responses in mice developing either spontaneous (transgenic) or transplanted MM as a consequence of the degree of tumor burden. Particularly striking were the profound B cell lymphopenia and the expansion of CD8(+) effector memory T cells within the lymphocyte population that progressively developed with advancing disease burden, mirroring changes seen in human MM. High disease burden was also associated with increased inflammatory cytokine production by T lymphocytes, which is more fitting with relapsed/refractory MM in humans. These findings have important implications for the application of this mouse model in the development of MM immunotherapies. Trial registration LitVacc ANZCTR trial ID ACTRN12613000344796; RevLite ANZCTR trial ID NCT00482261.

Common and distinct neural mechanisms of the fundamental dimensions of social cognition.

PubMed

Han, Mengfei; Bi, Chongzeng; Ybarra, Oscar

2016-01-01

In the present study, we used a valence classification task to investigate the common and distinct neural basis of the two fundamental dimensions of social cognition (agency and communion) using functional magnetic resonance imaging (fMRI). The results showed that several brain areas associated with mentalizing, along with the inferior parietal gyrus in the mirror system, showed overlap in response to both agentic and communal words. These findings suggest that both content categories are related to the neural basis of social cognition; further, several areas in the default mode network (DMN) showed similar deactivations between agency and communion, reflecting task-induced deactivation (TID). In terms of distinct activations, the findings indicated greater deactivations for communal than agentic content in the ventral anterior cingulate (vACC) and medial orbitofrontal cortex (mOFC). Communion also showed greater activation in some visual areas compared to agentic content, including occipital gyrus, lingual gyrus, and fusiform gyrus. These activations may reflect greater allocation of attentional resources to visual areas when processing communal content, or inhibition of cognitive activity irrelevant to task performance. If so, this suggests greater attention and engagement with communion-related content. The present research thus suggests common and differential activations for agency- versus communion-related content.

Self-identification and empathy modulate error-related brain activity during the observation of penalty shots between friend and foe

PubMed Central

Ganesh, Shanti; van Schie, Hein T.; De Bruijn, Ellen R. A.; Bekkering, Harold

2009-01-01

The ability to detect and process errors made by others plays an important role is many social contexts. The capacity to process errors is typically found to rely on sites in the medial frontal cortex. However, it remains to be determined whether responses at these sites are driven primarily by action errors themselves or by the affective consequences normally associated with their commission. Using an experimental paradigm that disentangles action errors and the valence of their affective consequences, we demonstrate that sites in the medial frontal cortex (MFC), including the ventral anterior cingulate cortex (vACC) and pre-supplementary motor area (pre-SMA), respond to action errors independent of the valence of their consequences. The strength of this response was negatively correlated with the empathic concern subscale of the Interpersonal Reactivity Index. We also demonstrate a main effect of self-identification by showing that errors committed by friends and foes elicited significantly different BOLD responses in a separate region of the middle anterior cingulate cortex (mACC). These results suggest that the way we look at others plays a critical role in determining patterns of brain activation during error observation. These findings may have important implications for general theories of error processing. PMID:19015079

Seroepidemiologic Survey of Varicella-Zoster Virus in Korean Adults Using Glycoprotein Enzyme Immuno Assay and Fluorescent Antibody to Membrane Antigen Test

PubMed Central

Kim, Yun Hwa; Hwang, Ji Young; Lee, Kyung Min; Choi, Jin Hee; Lee, Tae Yoon; Choi, Jong Soo

2011-01-01

Background Herpes zoster (HZ) occurs mainly in the elderly and Korea is rapidly becoming an aging society. Therefore, it is important to know the immune status against varicella-zoster virus (VZV) in Korean adults to prevent the disease. Objective The aim of this study was to survey the immune status of Korean adults over 40 years of age against VZV. Methods Antibody titer was measured using a VaccZyme™ VZV glycoprotein enzyme immunoassay (gpEIA) (Binding Site, UK). Fluorescent antibody to membrane antigen (FAMA) test was performed to measure the seropositive rate. Results HZ incidence in the 214 adults enrolled in this study was 10.3%. The gpEIA geometric mean titer (GMT) was 490 mIU/ml and 90.2% of the subjects had a protective level of gpEIA antibody titer against varicella. The average gpEIA GMT of adults who previously had HZ was 1,122 mIU/ml, which was higher than the average gpEIA GMT of 457 mIU/ml in adults who had not had HZ. The FAMA positive rate was 98.6%. Conclusion Most (90.2%) Korean adults ≥40-years-of-age have a protective level of gpEIA antibody against varicella and 98.6% were FAMA seropositive. The GMT of gpEIA antibody was significantly increased with age, and was higher in adults with a history of HZ. PMID:21738361

Antibody persistence at 18-20 months of age and safety and immunogenicity of a booster dose of a combined DTaP-IPV//PRP∼T vaccine compared to separate vaccines (DTaP, PRP∼T and IPV) following primary vaccination of healthy infants in the People's Republic of China.

PubMed

Li, Rong Cheng; Li, Feng Xiang; Li, Yan Ping; Hou, Qi Ming; Li, Chang Gui; Li, Ya Nan; Chen, Fu Sheng; Hu, Xue Zhong; Su, Wen Bin; Zhang, Shu Min; Fang, Han Hua; Ye, Qiang; Zeng, Tian De; Liu, Tao Xuan; Li, Xiu Bi; Huang, Yun Neng; Deng, Man Ling; Zhang, Yan Ping; Ortiz, Esteban

2011-11-21

This study assessed the antibody persistence, and the immunogenicity and safety of a booster dose of a DTaP-IPV//PRP∼T (Pentaxim®, Sanofi Pasteur's AcXim family) combined vaccine and of standalone vaccines one year after primary vaccination in the People's Republic of China. Participants (N=719) previously primed with DTaP-IPV//PRP∼T at 2, 3, 4 months (Group A, N=255), 3, 4, 5 months (Group B, N=233), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib®) and IPV (Imovax® Polio) at 3, 4, 5 months (Group C, N=231) received boosters of the same vaccines at 18-20 months of age. Seroprotection (SP) and seroconversion (SC) were determined before and 1 month after the booster. Safety was monitored from parental reports. In all groups 87.6-100% of participants had pre-booster protective anti-PRP, -diphtheria, -tetanus and -poliovirus antibody titers; post-booster, all SP rates were 100% and SC was ≥ 80.4% for anti-pertussis titers ≥ 4-fold increase. Reactogenicity was low for each group. These data support the use of the DTaP-IPV//PRP∼T vaccine in the People's Republic of China compared to separate DTaP, IPV, and PRP∼T administration in terms of both safety and immunogenicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Phase III randomized, double-blind, clinical trial of an investigational hexavalent vaccine given at 2, 4, and 11-12 months.

PubMed

Silfverdal, Sven-Arne; Icardi, Giancarlo; Vesikari, Timo; Flores, Sheryl A; Pagnoni, Marco F; Xu, Jin; Liu, G Frank; Stek, Jon E; Boisnard, Florence; Thomas, Stéphane; Ziani, Eddy; Lee, Andrew W

2016-07-19

Combination vaccines simplify vaccination visits and improve coverage and timeliness. DTaP5-HB-IPV-Hib is a new investigational, fully-liquid, combination vaccine designed to protect against 6 infectious diseases, including 5 pertussis antigens and OMPC instead of PT as conjugated protein for Hib component. In this multicenter, double-blind, comparator-controlled, Phase III study (NCT01480258) conducted in Sweden, Italy, and Finland, healthy infants were randomized 1:1 to receive one two immunization regimens. The DTaP5-HB-IPV-Hib Group received the investigational hexavalent vaccine (DTaP5-HB-IPV-Hib) and the Control Group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 4 and 11-12months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) or Rotarix (RV1) at 2, 4months of age and PCV13 at 11-12months. Subjects administered RV5 received a 3rd dose at 5months of age. A total of 656 subjects were randomized to the DTaP5-HB-IPV-Hib Group and 659 subjects to Control Group. Immune responses to all vaccine antigens post-toddler dose were non-inferior in the DTaP5-HB-IPV-Hib Group as compared to the Control Group. Additionally, the post-dose 2 and pre-toddler DTaP5-HB-IPV-Hib anti-PRP responses were superior. The DTaP5-HB-IPV-Hib Group responses to concomitant RV1 were non-inferior compared to the Control Group. Solicited adverse event rates after any dose were similar in both groups, except for higher rates of pyrexia (6.4% difference; 95% CI: 1.5,11.3) and somnolence (5.8% difference; 95% CI: 1.7,9.8) in the DTaP5-HB-IPV-Hib Group. Vaccine-related serious adverse events occurred infrequently in the DTaP5-HB-IPV-Hib Group (0.3%) and the Control Group (0.5%). The safety and immunogenicity of DTaP5-HB-IPV-Hib is generally comparable to Control when administered in the 2, 4, 11-12month schedule. Early Hib responses were superior versus Control. DTaP5-HB-IPV-Hib could provide a new hexavalent option for pediatric combination vaccines, aligned

Timing of routine infant vaccinations and risk of food allergy and eczema at one year of age.

PubMed

Kiraly, N; Koplin, J J; Crawford, N W; Bannister, S; Flanagan, K L; Holt, P G; Gurrin, L C; Lowe, A J; Tang, M L K; Wake, M; Ponsonby, A-L; Dharmage, S C; Allen, K J

2016-04-01

Epidemiological evidence suggests that routine vaccinations can have nontargeted effects on susceptibility to infections and allergic disease. Such effects may depend on age at vaccination, and a delay in pertussis vaccination has been linked to reduced risk of allergic disease. We aimed to test the hypothesis that delay in vaccines containing diphtheria-tetanus-acellular pertussis (DTaP) is associated with reduced risk of food allergy and other allergic diseases. HealthNuts is a population-based cohort in Melbourne, Australia. Twelve-month-old infants were skin prick-tested to common food allergens, and sensitized infants were offered oral food challenges to determine food allergy status. In this data linkage study, vaccination data for children in the HealthNuts cohort were obtained from the Australian Childhood Immunisation Register. Associations were examined between age at the first dose of DTaP and allergic disease. Of 4433 children, 109 (2.5%) received the first dose of DTaP one month late (delayed DTaP). Overall, delayed DTaP was not associated with primary outcomes of food allergy (adjusted odds ratio (aOR) 0.77; 95% CI: 0.36-1.62, P = 0.49) or atopic sensitization (aOR: 0.66; 95% CI: 0.35-1.24, P = 0.19). Amongst secondary outcomes, delayed DTaP was associated with reduced eczema (aOR: 0.57; 95% CI: 0.34-0.97, P = 0.04) and reduced use of eczema medication (aOR: 0.45; 95% CI: 0.24-0.83, P = 0.01). There was no overall association between delayed DTaP and food allergy; however, children with delayed DTaP had less eczema and less use of eczema medication. Timing of routine infant immunizations may affect susceptibility to allergic disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunogenicity and reactogenicity of Infanrix™ when co-administered with meningococcal MenACWY-TT conjugate vaccine in toddlers primed with MenHibrix™ and Pediarix™.

PubMed

Leonardi, Michael; Latiolais, Thomas; Sarpong, Kwabena; Simon, Michael; Twiggs, Jerry; Lei, Paul; Rinderknecht, Stephen; Blatter, Mark; Bianco, Veronique; Baine, Yaela; Friedland, Leonard R; Baccarini, Carmen; Miller, Jacqueline M

2015-02-11

Co-administration of an investigational quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) with the fourth dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP) at age 15-18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine (HibMenCY-TT)-primed toddlers. Infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine, or Hib-TT and DTaP-HBV-IPV (Control). HibMenCY-TT+ DTaP-HBV-IPV vaccinees were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months (MenACWY-TT group); MenACWY-TT co-administered with DTaP at 15-18 months (Coad group); or HibMenCY-TT at 12-15 months and DTaP at 15-18 months (HibMenCY-TT group). Controls received DTaP at 15-18 months. Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study. DTaP immunogenicity and reactogenicity were assessed one month post-vaccination. Pre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria, tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin. Following vaccination ≥99% of children had anti-diphtheria/anti-tetanus concentrations ≥1.0 IU/ml. Pertussis GMCs were lower in all investigational groups versus Control. In post hoc analyses, pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated (Schmitt, von König, et al., 1996; Schmitt, Schuind, et al., 1996). The reactogenicity profile of the Coad group was similar to DTaP administered alone. Routine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers. These data support the

Comparison of Three Enzyme-Linked Immunosorbent Assays for Detection of Immunoglobulin G Antibodies to Tetanus Toxoid with Reference Standards and the Impact on Clinical Practice▿

PubMed Central

van Hoeven, Karen H.; Dale, Connie; Foster, Phil; Body, Barbara

2008-01-01

Accurate determination of the concentrations of immunoglobulin G (IgG) antibody to tetanus toxoid is important in order to evaluate the immunogenicity of tetanus toxoid vaccines, determine immune competence in individual patients, and measure the prevalence of immunity in populations. The performance of three commercially available enzyme-linked immunosorbent assays (ELISAs) for IgG antibodies to tetanus toxoid were evaluated. Serially diluted NIBSC 76/589 and TE-3 human tetanus IgG immunoglobulin international reference standards were analyzed in quadruplicate using ELISAs manufactured by The Binding Site, Inc. (VaccZyme); Scimedx; and Euroimmun. In addition, IgG antibodies to tetanus toxoid were measured in 83 deidentified serum specimens using each manufacturer's ELISA. Each ELISA provided linear results when evaluated with the reference preparations. The Binding Site ELISA provided results that closely corresponded to the reference preparations (y = 1.09x − 0.08), whereas the Scimedx ELISA gave results that were consistently lower (y = 0.21x − 0.07) and the Euroimmun ELISA gave results that were consistently higher (y = 1.5x + 0.30) than the reference preparation concentrations. Using the recommended cutoff for each ELISA (<0.10 IU/ml), the overall agreement of all of the ELISA methods was 78%. Three of eighty-three (3.6%) human serum samples demonstrated inadequate immunity with all three assays. The Binding Site ELISA yielded nonprotective antibody concentrations in only these 3 samples, whereas 19 samples (22.9%) according to the Scimedx ELISA and 6 samples (7.2%) according to the Euroimmun ELISA demonstrated nonprotective concentrations. The performance characteristics of ELISAs for tetanus immunoglobulin titers were manufacturer dependent, and the differences translated into important disparities in reported results. PMID:18845832

Vaccinology capacity building in Europe for innovative platforms serving emerging markets.

PubMed

Hendriks, Jan; Holleman, Marit; Hamidi, Ahd; Beurret, Michel; Boog, Claire

2013-04-01

The 2012 Terrapinn World Vaccine Congress held from 16 to 18 October in Lyon addressed in a dedicated session the transfer of innovative vaccine technologies from Europe to emerging markets. Past and recent transfers and experiences from Europe's public domain were summarized by the Netherlands' National Institute for Public Health and the Environment (RIVM) in Bilthoven. The role of capacity building through training courses for developing country partners was highlighted in several recent technology transfer programs developed in collaboration with the World Health Organisation (WHO). In another stream of the Congress, a case of human vaccine technology transfer from Europe's private sector to an emerging economy recipient in India was presented. The continuing globalization of vaccinology is further illustrated by the recent acquisition in 2012 of the Netherlands' public vaccine manufacturing capacity in Bilthoven by the Serum Institute of India Ltd, an emerging vaccine manufacturer. In a parallel development, the Netherlands' government decided to transform RIVM's vaccinology research and development capacity into a new not-for-profit entity: "the Institute for Translational Vaccinology" (see citation 1 in Note section for web address). Under a public private partnership structure, InTraVacc's mission will include the fostering of global health through international partnerships in innovative vaccinology. Projected activities will include training courses and curricula, capitalizing on various currently established platform technologies and the legacy of previous "producer -producer" collaborations between the RIVM and emerging manufacturers over the past 40 y. It is suggested to consider this as a basis for a common initiative from Europe to develop and implement a practical vaccinology course for emerging countries with particular focus to the African region.

Vaccine antigens modulate the innate response of monocytes to Al(OH)3

PubMed Central

Brummelman, Jolanda; van Els, Cécile A. C. M.; Marino, Fabio; Heck, Albert J. R.; van Riet, Elly; Metz, Bernard; Kersten, Gideon F. A.; Pennings, Jeroen L. A.; Meiring, Hugo D.

2018-01-01

Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level. PMID:29813132

Systemic allergic reactions to gelatin included in vaccines as a stabilizer.

PubMed

Sakaguchi, M; Inouye, S

2000-10-01

Most of the children who showed systemic immediate-type reactions, including anaphylactic shock, to measles, mumps, rubella, and varicella vaccines had IgE antibodies to gelatin; thus we suspected that the allergic symptoms are caused by gelatin antigen, which is usually included in these live-virus vaccines as a stabilizer. We hypothesized that the anti-gelatin IgE is elicited by immunization with DTaP (diphtheria-tetanus-acellular pertussis) vaccines, which contained a small amount of gelatin as a spillover protein after purification of pertussis toxin. To test this hypothesis, we conducted a case-control study to determine whether children with anti-gelatin IgE had received gelatin-containing DTaP vaccines, and it was indeed found that all such children in the study had immunization histories that included the gelatin-containing DTaP vaccines. Based on these findings, the vaccine manufacturers had removed gelatin from all the DTaP and live-virus vaccines produced in Japan by 2000.

A clinical analysis of gelatin allergy and determination of its causal relationship to the previous administration of gelatin-containing acellular pertussis vaccine combined with diphtheria and tetanus toxoids.

PubMed

Nakayama, T; Aizawa, C; Kuno-Sakai, H

1999-02-01

The number of patients with allergic reactions after administration of gelatin-containing live vaccines is increasingly reported in Japan. These allergic reactions appear to be caused by gelatin allergy. It is still unknown how the patients were sensitized to gelatin. To determine the incidence of gelatin allergy and to identify contributing factors to gelatin allergy, we investigated the following clinical aspects: the development of IgE antibodies to gelatin and the relationship of the patients' past history of acellular pertussis vaccine combined with diphtheria and tetanus toxoid (DTaP) to the development of gelatin allergy. We evaluated 366 patient reports, submitted from 1994 to 1997, of adverse reactions after immunization with monovalent measles, mumps, and rubella vaccines containing 0.2% gelatin as stabilizer. On the basis of physician reports, the patients were categorized as to the nature of the adverse reaction. We determined the presence of IgE antibodies to gelatin and obtained past immunization history. The 366 reported patients were categorized as follows: 34 with anaphylaxis, 76 with urticaria, 215 with nonurticarial generalized eruption, and 41 with local reactions only. In 206 patients from whom serum was available, IgE antibodies to gelatin were detected in 25 of 27 (93%) with anaphylaxis, 27 of 48 (56%) with urticaria, and 8 of 90 (9%) with a generalized eruption. None of a group of 41 patients with only local reactions at the injected site and none of a control group of 29 subjects with no adverse reaction had such antibodies. Among 202 patients for whom prior vaccine information was available, all had received DTaP vaccines. Among those for whom the prior DTaP vaccine could be determined to contain gelatin or be free of gelatin, 155 of 158 (98%) subjects had received gelatin-containing DTaP vaccines. This rate is higher than would be expected on the basis of the market share of gelatin-containing (vs gelatin-free) DTaP vaccines (75

Hydrogen sulphide facilitates exocytosis by regulating the handling of intracellular calcium by chromaffin cells.

PubMed

de Pascual, Ricardo; Baraibar, Andrés M; Méndez-López, Iago; Pérez-Ciria, Martín; Polo-Vaquero, Ignacio; Gandía, Luis; Ohia, Sunny E; García, Antonio G; de Diego, Antonio M G

2018-05-02

Gasotransmitter hydrogen sulphide (H 2 S) has emerged as a regulator of multiple physiological and pathophysiological processes throughout. Here, we have investigated the effects of NaHS (fast donor of H 2 S) and GYY4137 (GYY, slow donor of H 2 S) on the exocytotic release of catecholamines from fast-perifused bovine adrenal chromaffin cells (BCCs) challenged with sequential intermittent pulses of a K + -depolarizing solution. Both donors caused a concentration-dependent facilitation of secretion. This was not due to an augmentation of Ca 2+ entry through voltage-activated Ca 2+ channels (VACCs) because, in fact, NaHS and GYY caused a mild inhibition of whole-cell Ca 2+ currents. Rather, the facilitation of exocytosis seemed to be associated to an augmented basal [Ca 2+ ] c and the K + -elicited [Ca 2+ ] c transients; such effects of H 2 S donors are aborted by cyclopiazonic acid (CPA), that causes endoplasmic reticulum (ER) Ca 2+ depletion through sarcoendoplasmic reticulum Ca2+ ATPase inhibition and by protonophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), that impedes the ability of mitochondria to sequester cytosolic Ca 2+ during cell depolarization. Inasmuch as CPA and FCCP reversed the facilitation of secretion triggered by K + in the presence of NaHS and GYY, is seems that such facilitation is tightly coupled to Ca 2+ handling by the ER and mitochondria. On the basis of these results, we propose that H 2 S regulates catecholamine secretory responses triggered by K + in BCCs by (i) mobilisation of ER Ca 2+ and (ii) interference with mitochondrial Ca 2+ circulation. In so doing, the clearance of the [Ca 2+ ] c transient will be delayed and the Ca 2+ -dependent trafficking of secretory vesicles will be enhanced to overfill the secretory machinery with new vesicles to enhance exocytosis.

Serum anti-tetanus and measles antibody titres in Ugandan children aged 4 months to 6 years: implications for vaccine programme.

PubMed

Warrener, Lenesha; Bwogi, Josephine; Andrews, Nick; Samuel, Dhanraj; Kabaliisa, Theopista; Bukenya, Henry; Brown, Kevin; Roper, Martha H; Featherstone, David A; Brown, David

2018-05-09

To study the antibody response to tetanus toxoid and measles by age following vaccination in children aged 4 months to 6 years in Entebbe, Uganda. Serum samples were obtained from 113 children aged 4-15 months, at the Mother-Child Health Clinic (MCHC), Entebbe Hospital and from 203 of the 206 children aged between 12 and 75 months recruited through the Outpatients Department (OPD). Antibodies to measles were quantified by plaque reduction neutralisation test (PRNT) and with Siemens IgG EIA. VaccZyme IgG EIA was used to quantify anti-tetanus antibodies. Sera from 96 of 113 (85.0%) children attending the MCHC contained Measles PRNT titres below the protective level (120 mIU/ml). Sera from 24 of 203 (11.8%) children attending the OPD contained PRNT titres 0.15 IU/ml by EIA, a level considered protective. The overall concentration of anti-tetanus antibody was sixfold higher in children under 12 months compared with the older children, with geometric mean concentrations of 3.15 IU/ml and 0.49 IU/ml, respectively. For each doubling in age between 4 and 64 months, the anti-tetanus antibody concentration declined by 50%. As time since the administration of the third DTP vaccination doubled, anti-tetanus antibody concentration declined by 39%. The low measles antibody prevalence in the children presenting at the MCHC is consistent with the current measles epidemiology in Uganda, where a significant number of measles cases occur in children under 1 year of age and earlier vaccination may be indicated. The consistent fall in anti-tetanus antibody titre over time following vaccination supports the need for further vaccine boosters at age 4-5 years as recommended by the WHO.

Effects of simultaneous immunization of Haemophilus influenzae type b conjugate vaccine and diphtheria-tetanus-acellular pertussis vaccine on anti-tetanus potencies in mice, guinea pigs, and rats.

PubMed

Fukuda, Tadashi; Iwaki, Masaaki; Komiya, Takako; Shibayama, Keigo; Takahashi, Motohide; Nakashima, Hideki

2013-01-01

Haemophilus influenzae type b vaccine conjugated with tetanus toxoid (HibT) was licensed for use in childhood immunization in Japan in 2007. As adsorbed diphtheria-tetanus-acellular pertussis (DTaP) combined with HibT vaccine has not been introduced in Japan, DTaP and HibT vaccines are injected at separate sites with a similar immunization schedule. There are various interfering or stimulatory effects between components of combined vaccines contained in DTaP and HibT vaccines. In this study, we investigated the effect of HibT containing combination vaccines on anti-tetanus potencies by using animal models (mouse, guinea pig, and rat). HibT vaccine and HibT components of imported DTaP-HibT vaccine alone showed comparable or higher anti-tetanus potency than DTaP vaccine and DTaP-containing components of combination vaccines. Mixing these components before injection resulted in potencies greater than the sum of individual potencies. Injecting individual components at separate sites in animals resulted in potency roughly equivalent to the sum of the individual potencies. These results provide useful information regarding the use of HibT-containing multivalent vaccines in childhood immunization.

Quadracel: Vaccination Against Diphtheria, Tetanus, Pertussis, and Poliomyelitis in Children.

PubMed

Mosley, Juan F; Smith, Lillian L; Parke, Crystal K; Brown, Jamal A; LaFrance, Justin M; Clark, Patricia K

2016-04-01

Vaccinations in school-aged children are required by state and local law to maintain high vaccination coverage rates, as well as low rates of vaccine-preventable diseases. Diphtheria, tetanus, and pertussis are childhood diseases that can be life threatening; poliomyelitis, another childhood disease, can be disabling. In turn, vaccinations were developed to provide protection against these diseases. Today, several vaccinations are recommended for children, including but not limited to diphtheria, tetanus, and pertussis (DTaP) and poliomyelitis (IPV). DTaP requires five doses, and IPV requires four. Quadracel (diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine, Sanofi Pasteur Inc.) is a new vaccination developed to condense the last dose of both DTaP and IPV so they do not have to be given separately, thus reducing the total number of vaccinations required. The Quadracel vaccine is an option for use in children who are completing the DTaP and IPV series. In a randomized, controlled, phase 3, pivotal trial, Quadracel proved to be as efficacious and safe as Daptacel (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed, Sanofi Pasteur Inc.) and IPOL (poliovirus vaccine inactivated, Sanofi Pasteur Inc.), given separately, to children between the ages of 4 and 6 years. Quadracel should be recommended to parents who have children between the ages of 4 and 6 years who meet the necessary administration criteria and need to finalize their DTaP and IPV series. Quadracel's administration in the vaccination series replaces one additional injection, which may benefit children who are afraid of receiving shots and parents who need to schedule one less doctor's appointment.

Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine and Guidance for Use as a Booster Dose.

PubMed

Liang, Jennifer; Wallace, Greg; Mootrey, Gina

2015-09-04

On March 24, 2015, the Food and Drug Administration licensed an additional combined diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP) and inactivated poliovirus (IPV) vaccine (DTaP-IPV) (Quadracel, Sanofi Pasteur Inc.). Quadracel is the second DTaP-IPV vaccine to be licensed for use among children aged 4 through 6 years in the United States (1). Quadracel is approved for administration as a fifth dose in the DTaP series and as a fourth or fifth dose in the IPV series in children aged 4 through 6 years who have received 4 doses of DTaP-IPV-Hib (Pentacel, Sanofi Pasteur) and/or DTaP (Daptacel, Sanofi Pasteur) vaccine (2,3). This report summarizes the indications for Quadracel vaccine and provides guidance from the Advisory Committee on Immunization Practices (ACIP) for its use.

Systematic review of reporting rates of adverse events following immunization: an international comparison of post-marketing surveillance programs with reference to China.

PubMed

Guo, Biao; Page, Andrew; Wang, Huaqing; Taylor, Richard; McIntyre, Peter

2013-01-11

China is the most populous country in the world, with an annual birth cohort of approximately 16 million, requiring an average of 500 million vaccine doses administered annually. In China, over 30 domestic and less than 10 overseas vaccine manufacturers supply over 60 licensed vaccine products, representing a growing vaccine market mainly due to recent additions to the national immunization schedule, but data on post-marketing surveillance for adverse events following immunization (AEFI) are sparse. To compare reporting rates for various categories of AEFI from China with other routine post-marketing surveillance programs internationally. Systematic review of published studies reporting rates of AEFI by vaccine, category of reaction and age from post-marketing surveillance systems in English and Chinese languages. Overall AEFI reporting rates (all vaccines, all ages) in Chinese studies were consistent with those from similar international studies elsewhere, but there was substantial heterogeneity in regional reporting rates in China (range 2.3-37.8/100,000 doses). The highest AEFI reporting rates were for diphtheria-tetanus-pertussis whole-cell (DTwP) and acellular (DTaP) vaccines (range 3.3-181.1/100,000 doses for DTwP; range 3.5-92.6/100,000 doses for DTaP), with higher median rates for DTwP than DTaP, and higher than expected rates for DTaP vaccine. Similar higher rates for DTwP and DTaP containing vaccines, and relatively lower rates for vaccines against hepatitis B virus, poliovirus, and Japanese encephalitis virus were found in China and elsewhere in the world. Overall AEFI reporting rates in China were consistent with similar post-marketing surveillance systems in other countries. Sources of regional heterogeneity in AEFI reporting rates, and their relationships to differing vaccine manufacturers versus differing surveillance practices, require further exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age.

PubMed

Trofa, Andrew F; Klein, Nicola P; Paul, Ian M; Michaels, Marian G; Goessler, Mary; Chandrasekaran, Vijayalakshmi; Blatter, Mark

2011-09-01

This study (NCT00197236) evaluated the safety and immunogenicity of a hepatitis A virus (HAV) vaccine when coadministered with diphtheria-tetanus-acellular pertussis (DTaP) and Haemophilus influenzae type b (Hib) vaccines in children 15 months of age. This was an open-labeled, multicenter study with healthy subjects enrolled and randomized (1:1:1) into 3 treatment groups. A total of 394 subjects received the first study vaccinations at 15 months of age. Group HAV (N = 135) received 2 doses of HAV vaccine 6 to 9 months apart. Group HAV+DTaP+Hib (N = 127) received HAV vaccine coadministered with DTaP and Hib vaccines and the second dose of HAV vaccine, 6 to 9 months later. Group DTaP+Hib→HAV (N = 132) received the DTaP and Hib vaccines at 15 months of age, followed by HAV vaccine 30 days later and the second dose of HAV vaccine 7 to 10 months after the DTaP+Hib vaccines. Immune responses were evaluated before the first study vaccination and 30 days after each vaccine dose. Solicited, unsolicited, and serious adverse events were collected. After 2 doses of the HAV vaccine, all subjects in the 3 groups were seropositive. The geometric mean concentration of anti-HAV antibodies ranged between 1625.1 and 1904.4 mIU/mL. Coadministration of the 3 vaccines did not impact immunogenicity of the HAV, DTaP, or Hib vaccines. Vaccines were well tolerated in all groups. A 2-dose schedule of HAV vaccine was well tolerated and immunogenic when administered to children starting at 15 months of age. Immune responses to the DTaP or Hib vaccines were similar whether they were administered alone or were coadministered with the HAV vaccine.

Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status

PubMed Central

Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y.; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong

2011-01-01

This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

Poor Immune Responses to a Birth Dose of Diphtheria, Tetanus, and Acellular Pertussis Vaccine

PubMed Central

Halasa, Natasha B.; O’Shea, Alice; Shi, Jian R.; Lafleur, Bonnie J.; Edwards, Kathryn M.

2013-01-01

Objectives To evaluate the safety and immunogenicity of an additional birth dose of diphtheria, tetanus, and acellular pertussis vaccine (DTaP). Study design Fifty infants between 2 to 14 days of age were randomly assigned to receive either DTaP and hepatitis B vaccines (experimental) or hepatitis B alone (control) at birth. At 2, 4, 6, and 17 months of age, DTaP and routine vaccines were administered to both groups. Safety data were collected after each dose, and sera were obtained at birth, 6, 7, 17, and 18 months. Immune responses to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae were measured by enzyme-linked immunosorbent assay; responses to other vaccines were assessed. Results No differences were seen between the 2 groups in either local or systemic reactions; all vaccines were well tolerated. Compared with the control group, infants in the experimental group demonstrated significantly lower geometric mean antibody concentrations for pertussis toxin and pertactin 6, 7, and 18 months, for fimbrae at 6, 7, 17, and 18 months, and for FHA at 18 months, and lower geometric mean antibody concentrations for diphtheria at 7 months. Immune responses to all other vaccine antigens were comparable. Conclusion Administration of an additional dose of DTaP at birth was safe but was associated with a significantly lower response to diphtheria and 3 of 4 pertussis antigens compared with controls. PMID:18534242

[Local reactions after diphtheria-tetanus-acellular pertussis vaccines in mice; changes in histopathology at the injection site].

PubMed

Nagaoka, Chiharu; Katsuta, Tomohiro; Honjo, Ayako; Tateyama, Satoshi; Tokutake, Tadaomi; Arimoto, Yutaka; Nakajima, Natsuki; Goshima, Toshiro; Kato, Tatsuo

2006-03-01

Diphtheria-tetanus-acellular pertussis vaccine (DTaP) developed in Japan is now widely used worldwide. DTaP is safer than the diphtheria-tetanus-whole-cell pertussis vaccine (DTwP) and has fewer severe side effects, but local reactions such as redness, swelling, and induration are still reported. The pathophysiological mechanism of these reactions is controversial. To clarify the cause of local reactions, we conducted studies using the mouse model. After administering either one or two abdominal subcutaneous DTaP inoculations, we observed changes in histopathology at the injection site at 24h, 48h, and 7 days. The control group, inoculated with physiologic saline, showed no significant changes either pathologically or with the naked eye. All mice after DTaP vaccination showed indurations at the injection site. Pathologically, we watched leukocyte invasion into or around the site, especially neutrophils and eosinophils. After the first vaccination, the extent of the invasion was strong 24h and 7 days later. At 24h following the second vaccination, a dramatic leukocyte invasion seen persisted at 7days. At 7 days after the first vaccination, peripheral fibrosis had begun, and when a second vaccination was administered, it began even earlier at the second site. These histopathological changes show that local reactions are caused by both inflammatory and allergic responses. Because this mouse study resulted in the same pattern of reactions observed in humans, this method will be useful for studies focusing on local reactions.

Measurement of Typhi Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency.

PubMed

Evans, C; Bateman, E; Steven, R; Ponsford, M; Cullinane, A; Shenton, C; Duthie, G; Conlon, C; Jolles, S; Huissoon, A P; Longhurst, H J; Rahman, T; Scott, C; Wallis, G; Harding, S; Parker, A R; Ferry, B L

2018-01-29

Vaccine-specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens, but interpretation may be complicated. Typhim Vi ® , a polysaccharide vaccine for Salmonella typhoid fever, may be an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multi-centre study describing the analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) calibrated to an affinity-purified Typhi Vi IgG preparation. Intra- and interassay imprecision was low and the assay was linear, between 7·4 and 574 U/ml (slope = 0·99-1·00; R 2  > 0·99); 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations  > 7·4 U/ml, the concentration range was 7·7-167 U/ml. In antibody-deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were  < 25 U/ml. In vaccinated normal healthy volunteers, the median concentration post-vaccination was 107 U/ml (range 31-542 U/ml). Eight of eight patients (100%) had post-vaccination concentration increases of at least threefold and six of eight (75%) of at least 10-fold. In an antibody-deficient population (n = 23), only 30% had post-vaccination concentration increases of at least threefold and 10% of at least 10-fold. The antibody responses to Pneumovax II and Typhim Vi ® correlated. We conclude that IgG responses to Typhim Vi ® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies. © 2018 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Quadrivalent meningococcal (MenACWY-TT) conjugate vaccine or a fourth dose of H. influenzae-N. meningitidis C/Y conjugate vaccine (HibMenCY-TT) is immunogenic in toddlers who previously received three doses of HibMenCY-TT in infancy.

PubMed

Leonardi, Michael; Latiolais, Thomas; Sarpong, Kwabena; Simon, Michael; Twiggs, Jerry; Lei, Paul; Rinderknecht, Stephen; Blatter, Mark; Bianco, Veronique; Baine, Yaela; Friedland, Leonard R; Miller, Jacqueline M

2015-02-11

Immunogenicity and safety of a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT were evaluated in the second year of life in HibMenCY-TT-primed toddlers. Healthy infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine; or Hib-TT and DTaP-HBV-IPV (control). Recipients of HibMenCY-TT+DTaP-HBV-IPV were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months; MenACWY-TT co-administered with DTaP at 15-18 months; or HibMenCY-TT at 12-15 months and DTaP at 15-18 months. Controls received DTaP only at 15-18 months due to Hib conjugate vaccine shortage. Serum bactericidal activity using human complement (hSBA) and safety were assessed one month after meningococcal vaccination. After vaccination with MenACWY-TT at 12-15 months or MenACWY-TT+DTaP at 15-18 months, all subjects previously primed for serogroups C/Y had hSBA ≥1:8 for these serogroups. At least 96.1% also had hSBA ≥1:8 for serogroups A/W. All subjects in the HibMenCY-TT group had hSBA ≥1:8 for serogroups C/Y. All pre-defined statistical criteria for meningococcal immunogenicity were satisfied. All vaccination regimens had acceptable safety profiles. Children primed with three doses of HibMenCY-TT who then received a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT had robust increases in hSBA titers for serogroups C/Y. These data provide support that MenACWY-TT, given with or without the fourth scheduled dose of DTaP could be administered as an alternative to a fourth dose of HibMenCY-TT in the second year of life. This study (110870/110871) is registered at www.clinicaltrials.gov NCT00614614. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immunogenicity and safety of a combined diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine (DTaP-IPV) compared to separate administration of standalone DTaP and IPV vaccines: a randomized, controlled study in infants in the Republic of Korea.

PubMed

Lee, Soo Young; Hwang, Hui Sung; Kim, Jong Hyun; Kim, Hyun Hee; Lee, Hyun Seung; Chung, Eun Hee; Park, Su Eun; Ma, Sang Hyuk; Chang, Jin Keun; Guitton, Fabrice; Ortiz, Esteban; Kang, Jin Han

2011-02-11

This randomized trial enrolled 442 infants in the Republic of Korea to assess the immunogenicity and safety of a combined diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine (DTaP-IPV; Tetraxim™) for primary vaccination at 2, 4 and 6 months of age compared with DTaP and IPV vaccines given separately. Immunogenicity was high in both groups; seroprotection and seroconversion rates of the combined vaccine (Group A) were non-inferior to the control vaccines (Group B). All subjects were seroprotected against poliovirus types 1, 2 and 3 (≥ 81/dil) and anti-diphtheria (≥ 0.01 IU/mL); 99.0% were seroprotected against tetanus (≥ 0.1 IU/mL). At least 93.6% had anti-diphtheria antibody titers ≥ 0.1 IU/mL. Anti-pertussis toxoid (PT) and anti-filamentous haemagglutinin (FHA) seroconversion (≥ 4-fold increase in antibody titer) rates were 96.6% and 94.4% for Group A, 92.2% and 78.4% for Group B. Most solicited reactions occurred within 4 days of vaccination, resolved within 3 days and were mild. Severe solicited reactions occurred after ≤ 0.5% of doses in Group A and ≤ 0.9% in Group B. No withdrawals occurred because of adverse events. The DTaP-IPV combined vaccine given at 2, 4, and 6 months of age was well tolerated; immunogenicity was similar to the control vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acellular pertussis vaccine boosters combined with diphtheria and tetanus toxoid boosters for adolescents: safety and immunogenicity assessment when preceded by different 5-dose DTaP/DTwP schedules.

PubMed

Pichichero, Michael E; Casey, Janet R; Francis, Anne B; Marsocci, Steven M; Murphy, Marie; Hoeger, William; Cleary, Carolyn

2006-09-01

A sixth dose of tetanus, diphtheria, acellular pertussis (Tdap) vaccine in adolescents might produce a differing reactogenicity and/or immunogenicity response depending on the composition of the 5 prior doses of DTaP or DT-whole cell pertussis (DTwP) vaccine. Reactions and immune responses following receipt of the Sanofi Pasteur (Adacel) and GlaxoSmithKline (Boostrix) Tdap vaccines were assessed in 229 adolescents. No differences were observed for reactions to either Tdap vaccine regardless of the prior DTaP/DTwP vaccination history. Seroprotective levels and antibody concentrations were comparable regardless of prior DTaP/DTwP vaccine history. A sixth sequential dose of Tdap after 5 doses of DTaP appears safe and immunogenic.

Booster Vaccination: The Role of Reduced Antigen Content Vaccines as a Preschool Booster

PubMed Central

Conversano, Michele; Zivelonghi, Giambattista; Zoppi, Giorgio

2014-01-01

The need for boosters for tetanus, diphtheria, pertussis, and polio, starting from preschool age, is related to the waning immune protection conferred by vaccination, the elimination/reduction of natural boosters due to large-scale immunization programs, and the possibility of reintroduction of wild agents from endemic areas. Taking into account the relevance of safety/tolerability in the compliance with vaccination among the population, it have been assessed whether today enough scientific evidences are available to support the use of dTap-IPV booster in preschool age. The review of the literature was conducted using the PubMed search engine. A total of 41 works has been selected; besides, the documentation produced by the World Health Organization, the European Centre for Disease Control, and the Italian Ministry of Health has been consulted. Many recent papers confirm the opportunity to use a low antigenic dose vaccine starting from 4 to 6 years of age. There is also evidence that 10 years after immunization the rate of seroprotected subjects against diphtheria does not differ significantly between those vaccinated with paediatric dose (DTaP) or reduced dose (dTaP or dTap) product. The dTpa vaccine is highly immunogenic for diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1 schedules). PMID:24678509

Effects of a Diphtheria-Tetanus-Acellular Pertussis Vaccine on Immune Responses in Murine Local Lymph Node and Lung Allergy Models▿

PubMed Central

Vandebriel, Rob J.; Gremmer, Eric R.; van Hartskamp, Michiel; Dormans, Jan A. M. A.; Mooi, Frits R.

2007-01-01

We have previously shown that in mice, diphtheria-tetanus-acellular pertussis (DTaP) vaccination before Bordetella pertussis infection resulted in, besides effective clearance, immediate hypersensitivity (lung eosinophilia, increased total serum immunoglobulin E [IgE], and increased ex vivo Th2 cytokine production by cells from the bronchial lymph nodes). To better appreciate the extent of these findings, we measured DTaP vaccination effects in the local lymph node assay (LLNA) and an ovalbumin (OVA) lung allergy model. In the LLNA, mice were vaccinated or adjuvant treated before being sensitized with trimellitic anhydride (TMA; inducing a Th2-directed response) and dinitrochlorobenzene (DNCB; inducing a Th1-directed response). Compared to the adjuvant-treated controls, the vaccinated mice showed a decreased response to TMA and (to a much lesser extent) an increased response to DNCB. The decreased response to TMA coincided with increased transforming growth factor β levels. With the exception of filamentous hemagglutinin, all vaccine constituents contributed to the decreased response to TMA. In the lung allergy model, sensitization induced OVA-specific IgE, lung pathology (peribronchiolitis, perivasculitis, and hypertrophy of the bronchiolar mucus cells) and increased the number of eosinophils, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Vaccination failed to modulate these parameters. In conclusion, although DTaP vaccination may affect the LLNA response, we found no evidence of an effect on lung allergy. PMID:17202304

Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

PubMed

Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

2013-07-15

Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

Tetanus, Diphtheria, and Pertussis Vaccines

MedlinePlus

... nose and throat. Whooping cough causes uncontrollable coughing. Vaccines can protect you from these diseases. In the U.S., there are four combination vaccines: DTaP prevents all three diseases. It is for ...

Your Baby's First Vaccines

MedlinePlus

... Link Vaccines & Immunizations Immunization Schedules Your Child's First Vaccines Format: Select One PDF [336K] RTF [260K] Recommend ... child will get one or more of these vaccines today: DTaP Hib Hepatitis B Polio PCV13 Why ...

Your child's first vaccines

MedlinePlus

... or more of these vaccines today: [ ] DTaP [ ] Hib [ ] Hepatitis B [ ] Polio [ ] PCV13 (Provider: Check appropriate boxes) 1. Why ... are at greatest risk for Hib disease. 5. Hepatitis B Signs and symptoms include tiredness, diarrhea and vomiting, ...

Safety and Immunogenicity of Tetanus Diphtheria and Acellular Pertussis (Tdap) Immunization During Pregnancy in Mothers and Infants: A Randomized Clinical Trial

PubMed Central

Munoz, Flor M.; Bond, Nanette H.; Maccato, Maurizio; Pinell, Phillip; Hammill, Hunter A.; Swamy, Geeta K.; Walter, Emmanuel B.; Jackson, Lisa A.; Englund, Janet A.; Edwards, Morven S.; Healy, C. Mary; Petrie, Carey R.; Ferreira, Jennifer; Goll, Johannes B.; Baker, Carol J.

2015-01-01

Importance Maternal immunization with tetanus toxoid and reduced diphtheria toxoid acellular pertussis (Tdap) vaccine could prevent infant pertussis. The effect of vaccine-induced maternal antibodies on infant responses to diphtheria and tetanus toxoids acellular pertussis (DTaP) immunization is unknown. Objective To evaluate the safety and immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to DTaP. Design, Setting and Participants Phase I, randomized, double-masked, placebo-controlled clinical trial conducted in private (Houston) and academic (Durham, Seattle) obstetric practices from 2008 to 2012. Forty eight healthy 18–45 year-old pregnant women received Tdap (n=33) or placebo (n=15) at 30–32 weeks’ gestation with cross-over Tdap immunization postpartum. Interventions Tdap vaccination at 30–32 weeks’ gestation or post-partum. Outcome Measures Primary: Maternal and infant adverse events, pertussis illness and infant growth and development (Bayley-III screening test) until 13 months of age. Secondary: Antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months postpartum, and in infants at birth, 2 months, and after the third (7 months) and fourth (13 months) doses of DTaP. Results All participants delivered healthy newborns. No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 78.8% (95% CI: 61.1%, 91.0%) and 80% (CI: 51.9%, 95.7%) pregnant and postpartum women, respectively. Injection site pain was the predominant symptom. Systemic symptoms were reported in 36.4% (CI: 20.4%, 54.9%) and 73.3% (CI: 44.9%, 92.2%) pregnant and postpartum women, respectively. Malaise and myalgia were most common. Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in

72 FR 56765 - Proposed Consolidated Vaccine Information Materials for Multiple Infant Vaccines

Federal Register 2010, 2011, 2012, 2013, 2014

2007-10-04

... to meningitis (infection of the brain and spinal cord coverings); pneumonia; infections of the blood... vaccines: DTaP, Haemophilus influenzae type b, inactivated polio vaccine, pneumococcal conjugate vaccine... to administration of any of these vaccines. Hepatitis B, Haemophilus influenzae type b (Hib...

Childhood Vaccines: What They Are and Why Your Child Needs Them

MedlinePlus

... vaccine? The DTaP vaccine is 3 vaccines in 1 shot. It protects against diphtheria, tetanus and pertussis. It’s ... mumps, and rubella (MMR). It’s given as 2 shots when your child is 1 year old and again when they are 4- ...

Removal of gelatin from live vaccines and DTaP-an ultimate solution for vaccine-related gelatin allergy.

PubMed

Kuno-Sakai, Harumi; Kimura, Mikio

2003-12-01

From the early 1990s infants started to receive acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) before live vaccines such as measles, rubella, and mumps vaccines, which contained gelatin as a stabilizer. Then, an increasing number of cases of anaphylactic/allergic reactions to those live vaccines were reported. Almost all these cases had a previous history of receiving three or four doses of DTaP containing gelatin.Anaphylactic/allergic reactions to live measles vaccine were analyzed using information obtained from the Reporting System, a retrospective study, as well as from the Monitoring System, a prospective study. Dramatic decreases in anaphylactic/allergic reactions to live measles vaccines were observed immediately after each manufacturer marketed gelatin-free or gelatin (hypo-allergic)-containing live measles vaccine, and since the end of 1998 reports on anaphylactic/allergic reactions to live measles vaccine have almost ceased.

Your Baby's First Vaccines: What You Need to Know

MedlinePlus

... child will get these vaccines today:  DTaP  Hib  Hepatitis B (Provider: Check appropriate boxes.)  Polio  PCV13 1 Why ... are at greatest risk for Hib disease. 5. Hepatitis B • Signs and symptoms include tiredness, diarrhea and vomiting, ...

Mixing State and Optical Properties of Biomass Burning Aerosol during the SAMBBA 2012 Campaign

NASA Astrophysics Data System (ADS)

Brooke, Jennifer; Brooks, Barbara; McQuaid, Jim; Osborne, Simon

2013-04-01

Emissions of black carbon are a global phenomenon associated with combustion activities with an estimated 40 % of global emissions from biomass burning. These emissions are typically dominated in regional hotspots, such as along the edges of the Amazon Basin, and contribute to the regional air quality and have associated health impacts as well as the global climatic impacts of this major source of black carbon as well as other radiatively active species. New airborne measurements will be presented of biomass burning emissions across the Amazon region from the South AMerican Biomass Burning Analysis (SAMBBA) campaign based at Porto Vehlo, Rondônia, Brazil in September 2012. This airborne campaign aboard the FAAM BAe-146 coincided with the seasonal peak in South American biomass burning emissions, which make up the most dominant source of atmospheric pollutants in the region at this time. SAMBBA included dedicated flights involving in-situ measurements and remote sensing of single plume studies through to multi-plume sampling of smouldering and flaming vegetation fires, regional haze sampling, and measurements of biogenic aerosol and gases across Amazonas. This presentation summarises early findings from the SAMBBA aircraft observations focusing on the relationship between biomass burning aerosol properties; size distributions, aerosol mixing state and optical properties from a suite of instruments onboard the FAAM BAe-146. The interplay of these properties influences the regional radiative balance impacting on weather and climate. The Leeds airborne VACC (Volatile Aerosol Concentration and Composition) instrument is designed to investigate the volatility properties of different aerosol species in order to determine aerosol composition; furthermore it can be used to infer the mixing state of the aerosol. Size distributions measured with the volatility system will be compared with ambient size distribution measurements this allows information on organic coating

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due to Bordetella pertussis and Other Bordetella Subspecies

PubMed Central

Mattoo, Seema; Cherry, James D.

2005-01-01

Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation of B. pertussis. Future studies should seek to determine the cause of the unique cough which is associated with Bordetella respiratory infections. It is also hoped that data gathered from molecular Bordetella research will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines. PMID:15831828

Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

MedlinePlus

Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

73 FR 50821 - Consolidated Vaccine Information Materials for Multiple Infant Vaccines; Revised Instructions for...

Federal Register 2010, 2011, 2012, 2013, 2014

2008-08-28

... symptoms. There may be no signs or symptoms in mild cases. It can lead to meningitis (infection of the... chest pain. It can lead to meningitis (infection of the brain and spinal cord coverings), blood... information statements for the following childhood vaccines: DTaP, Haemophilus influenzae type b, inactivated...

Tetanus: Questions and Answers

MedlinePlus

... body. In recent years, a higher proportion of cases had minor wounds than had ma- jor ones, probably because severe wounds were more likely to ... the benefit of immunization outweighs the risk (for example, during a ... who developed one of these adverse events after pediatric DTaP vaccine ...

Immunogenicity and safety after booster vaccination of diphtheria, tetanus, and acellular pertussis in young adults: an open randomized controlled trial in Japan.

PubMed

Hara, Megumi; Okada, Kenji; Yamaguchi, Yuko; Uno, Shingo; Otsuka, Yasuko; Shimanoe, Chisato; Nanri, Hinako; Horita, Mikako; Ozaki, Iwata; Nishida, Yuichiro; Tanaka, Keitaro

2013-12-01

The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.).

Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness.

PubMed

Ohfuji, Satoko; Okada, Kenji; Nakano, Takashi; Ito, Hiroaki; Hara, Megumi; Kuroki, Haruo; Hirota, Yoshio

2017-08-24

When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR=0.11, 95% CI, 0.01-0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR=0.07, 95%CI, 0.01-0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR=5.67) and those with a recent contact with a lasting cough (OR=4.12). When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Influenza Vaccine, Inactivated or Recombinant

MedlinePlus

... flu vaccine. This risk has been estimated at 1 or 2 additional cases per million people vaccinated. This is much lower than the risk of severe complications from flu, which can be prevented by flu vaccine. Young children who get the flu shot along with pneumococcal vaccine (PCV13) and/or DTaP ...

Characteristics of pertussis outbreaks in Catalonia, Spain, 1997 to 2010.

PubMed

Crespo, Inma; Broner, Sonia; Soldevila, Núria; Martínez, Ana; Godoy, Pere; Sala-Farré, Maria-Rosa; Company, Maria; Rius, Cristina; Domínguez, Angela; Group Of Catalonia, The Pertussis Working

2015-01-01

In Catalonia, pertussis outbreaks must be reported to the Department of Health. This study analyzed pertussis outbreaks between 1997 and 2010 in general and according to the characteristics of the index cases. The outbreak rate, hospitalization rate and incidence of associated cases and their 95%CI were calculated. Index cases were classified in two groups according to age (<15 years and ≥15 years) and the vaccine type received: whole cell vaccine (DTwP) or acellular vaccine (DTaP). During the study period, 230 outbreaks were reported. The outbreak rate was 2.43 × 10(-6) persons-year, and outbreaks ranged from 2 to 32 cases, with a median duration of 18 days. There were 771 associated cases, with an incidence rate of 0.8 × 10(-5) persons-year.   After classifying outbreaks according to the age of the index case, 126 outbreaks (1.3 × 10(-6) persons-year) had an index case aged <15 y and 87 (0.87 × 10(-6) person-year) had an index case aged ≥15 y (RR = 1.44, 95%CI 1.10-1.90; P = 0.007). Between 2003 and 2010, after the introduction of the acellular vaccine, the index case was vaccinated with DTwP vaccine in 25 outbreaks (0.43 × 10(-6) persons-year) and with DTaP vaccine in 32 outbreaks (0.55 × 10(-6) person-year) (RR = 0.78, 95%CI 0.46-1.31; P = 0.35). Of cases, 37.2% were correctly vaccinated, suggesting waning immunity of pertussis vaccine protection and endogenous circulation of pertussis. A greater number of outbreaks had an index case aged <15 y. No changes in the disease incidence, associated cases and hospitalization rate were observed after the introduction of DTaP.

Characteristics of pertussis outbreaks in Catalonia, Spain, 1997 to 2010

PubMed Central

Crespo, Inma; Broner, Sonia; Soldevila, Núria; Martínez, Ana; Godoy, Pere; Sala-Farré, Maria-Rosa; Company, Maria; Rius, Cristina; Domínguez, Angela; Group of Catalonia, the Pertussis Working

2014-01-01

In Catalonia, pertussis outbreaks must be reported to the Department of Health. This study analyzed pertussis outbreaks between 1997 and 2010 in general and according to the characteristics of the index cases. The outbreak rate, hospitalization rate and incidence of associated cases and their 95%CI were calculated. Index cases were classified in two groups according to age (<15 years and ≥15 years) and the vaccine type received: whole cell vaccine (DTwP) or acellular vaccine (DTaP). During the study period, 230 outbreaks were reported. The outbreak rate was 2.43 × 10−6 persons-year, and outbreaks ranged from 2 to 32 cases, with a median duration of 18 days. There were 771 associated cases, with an incidence rate of 0.8 × 10−5 persons-year. After classifying outbreaks according to the age of the index case, 126 outbreaks (1.3 × 10−6 persons-year) had an index case aged <15 y and 87 (0.87 × 10−6 person-year) had an index case aged ≥15 y (RR = 1.44, 95%CI 1.10–1.90; P = 0.007). Between 2003 and 2010, after the introduction of the acellular vaccine, the index case was vaccinated with DTwP vaccine in 25 outbreaks (0.43 × 10−6 persons-year) and with DTaP vaccine in 32 outbreaks (0.55 × 10−6 person-year) (RR = 0.78, 95%CI 0.46–1.31; P = 0.35). Of cases, 37.2% were correctly vaccinated, suggesting waning immunity of pertussis vaccine protection and endogenous circulation of pertussis. A greater number of outbreaks had an index case aged <15 y. No changes in the disease incidence, associated cases and hospitalization rate were observed after the introduction of DTaP. PMID:25483541

Effectiveness of acellular pertussis vaccination during childhood (<7 years of age) for preventing pertussis in household contacts 1-9 years old in Catalonia and Navarra (Spain).

PubMed

Plans, P; Toledo, D; Sala, M R; Camps, N; Villanova, M; Rodríguez, R; Alvarez, J; Solano, R; García-Cenoz, M; Barrabeig, I; Godoy, P; Minguell, S

2016-12-01

Pertussis vaccination with 4-5 doses of acellular vaccines is recommended in Spain to all children at 2 months to 6 years of age. The effectiveness of the acellular pertussis vaccination was assessed in this study by comparing the incidence of secondary pertussis in vaccinated (4-5 doses) and unvaccinated or partially vaccinated (0-3 doses) household contacts 1-9 years old of confirmed cases of pertussis in Spain in 2012-13. Eighty-five percent of contacts had been vaccinated with 4-5 doses of acellular pertussis vaccines. During the 2-year study period, 64 cases of secondary pertussis were detected among 405 household contacts 1-9 years old: 47 among vaccinated and 17 among unvaccinated or partially vaccinated contacts. The effectiveness for preventing secondary pertussis, calculated as 1 minus the relative risk (RR) of secondary pertussis in vaccinated vs. unvaccinated/partially vaccinated contacts, was 50 % [95 % confidence interval (CI): 19-69 %, p < 0.01] when household contacts were vaccinated using DTaP, Tdap, hexavalent or heptavalent vaccines, and it was 51.3 % (95 % CI: 21-70 %, p < 0.01) when they were vaccinated using DTaP or TdaP vaccines. The effectiveness adjusted for age, sex, pertussis chemotherapy and type of household contact was 58.6 % (95 % CI: 17-79 %, p < 0.05) when contacts were vaccinated using available acellular vaccines, and it was 59.6 % (95 % CI: 18-80 %, p < 0.01) when they were vaccinated using DTaP vaccines. Acellular pertussis vaccination during childhood was effective for preventing secondary pertussis in household contacts 1-9 years old of pertussis cases in Catalonia and Navarra, Spain.

Influenza (Flu) Vaccine (Inactivated or Recombinant): What You Need to Know

MedlinePlus

... flu vaccine. This risk has been estimated at 1 or 2 additional cases per million people vaccinated. This is much lower than the risk of severe complications from flu, which can be prevented by flu vaccine. • Young children who get the flu shot along with pneumococcal vaccine (PCV13) and/or DTaP ...

[Whooping cough in Spain. Current epidemiology, prevention and control strategies. Recommendations by the Pertussis Working Group].

PubMed

Campins, Magda; Moreno-Pérez, David; Gil-de Miguel, Angel; González-Romo, Fernando; Moraga-Llop, Fernando A; Arístegui-Fernández, Javier; Goncé-Mellgren, Anna; Bayas, José M; Salleras-Sanmartí, Lluís

2013-04-01

A large increase of pertussis incidence has been observed in recent years in countries with high vaccination coverage. Outbreaks of pertussis are increasingly being reported. The age presentation has a bipolar distribution: infants younger 6months that have not initiated or completed a vaccination schedule, and adolescents and adults, due to the lost of natural or vaccine immunity over time. These epidemiological changes justify the need to adopt new vaccination strategies in order to protect young infants and to reduce pertussis incidence in all age groups. Adolescents and adults immunization must be a priority. In the first group, strategy is easy to implement, and with a very low additional cost (to replace dT vaccine by dTap one). Adult vaccination may be more difficult to implement; dT vaccine decennial booster should be replaced by dTap. The immunization of household contacts of newborn infants (cocooning) is the strategy that has a most important impact on infant pertussis. Recently, pregnant women vaccination (after 20weeks of gestation) has been recommended in some countries as the most effective way to protect the newborn. Copyright © 2012 Elsevier España, S.L. All rights reserved.

[Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar) booster dose in healthy Chinese toddlers].

PubMed

Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping

2009-06-01

To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.

Kaiser Permanente Northern California pregnancy database: Description and proof of concept study.

PubMed

Zerbo, Ousseny; Chan, Berwick; Goddard, Kristin; Lewis, Ned; Bok, Karin; Klein, Nicola P; Baxter, Roger

2016-11-04

We describe the establishment of a dynamic database linking mothers to newborns with the goal of studying vaccine safety in both pregnant women and their children and provide results of a study utilizing this database as a proof of concept. All Kaiser Permanente Northern California (KPNC) live births and their mothers were eligible for inclusion in the pregnancy database. We used the medical record number (MRN), a unique identifier, to retrieve information about events that occurred during the pregnancy and at delivery and linked this same MRN to newborns for post-partum follow up. We conducted a retrospective cohort study to evaluate the association between receipt of tetanus, diphtheria and acellular pertussis (Tdap) vaccine during pregnancy and fever 0-3days after the first dose of diphtheria tetanus and acellular pertussis (DTaP) vaccine in the infant. The study included infants who were born at ⩾37weeks gestation from January 1, 2009 - October 1, 2015 and who received their first DTaP vaccine between 6 and 10weeks of age. We utilized diagnostic codes from inpatient, emergency department, outpatient clinics, and telephone calls. We identified fever using ICD 9 code 780.6, recorded temperature ⩾101 degree Fahrenheit, or parental report. The database contained the starting and ending date of each pregnancy and basic demographic characteristics of mothers and infants. There were 859,699 women and 873,753 children in the database as of January 2016. The proof of concept study included 148,699 infants. In a multivariable logistic regression analysis, Tdap vaccination during pregnancy was not associated with infant fever 0-3daysafter first dose of DTaP (adjusted odds ratio=0.92, 95% CI 0.82-1.04). The KPNC pregnancy database can be used for studies investigating exposure during pregnancy and outcomes in mothers and/or infants, particularly monitoring vaccine safety and effectiveness. Copyright © 2016 Elsevier Ltd. All rights reserved.

An ecological analysis of pertussis disease in Minnesota, 2009-2013.

PubMed

Iroh Tam, P Y; Menk, J S; Hughes, J; Kulasingam, S L

2016-03-01

The increase in pertussis cases in Minnesota in the last decade has been mainly attributed to the switch from whole cell to acellular pertussis [as part of the diphtheria, tetanus and acellular pertussis vaccine (DTaP)]. It is unclear, however, to what degree community-level risk factors also contribute. Understanding these factors can help inform public health policy-makers about where else to target resources. We performed an ecological analysis within Minnesota to identify risk factors at the county level using a Bayesian Poisson generalized linear areal model to account for spatial dependence. Univariate analyses suggested an association between increased pertussis rates at the county level and white maternal ethnicity, being US born, urban counties and average household size. In the multivariable analysis, the rate of pertussis was 1·79 times greater for urban vs. rural counties and 4·75 times greater for counties with a one-person larger average household size. Pertussis rates in counties with higher (i.e. 4+DTaP) receipt in children were 0·97 times lower. Examining county-level factors associated with varying levels of pertussis may help identify those counties that would most benefit from targeted interventions and increased resource allocation.

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

PubMed

Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

2016-08-31

Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the

Development of a freeze-stable formulation for vaccines containing aluminum salt adjuvants.

PubMed

Braun, LaToya Jones; Tyagi, Anil; Perkins, Shalimar; Carpenter, John; Sylvester, David; Guy, Mark; Kristensen, Debra; Chen, Dexiang

2009-01-01

Vaccines containing aluminum salt adjuvants are prone to inactivation following exposure to freeze-thaw stress. Many are also prone to inactivation by heat. Thus, for maximum potency, these vaccines must be maintained at temperatures between 2 degrees C and 8 degrees C which requires the use of the cold chain. Nevertheless, the cold chain is not infallible. Vaccines are subject to freezing during both transport and storage, and frozen vaccines are discarded (under the best circumstances) or inadvertently administered despite potentially reduced potency. Here we describe an approach to minimize our reliance on the proper implementation of the cold chain to protect vaccines from freeze-thaw inactivation. By including PEG 300, propylene glycol, or glycerol in a hepatitis B vaccine, particle agglomeration, changes in the fluorescence emission spectrum--indicative of antigen tertiary structural changes--and losses of in vitro and in vivo indicators of potency were prevented following multiple exposures to -20 degrees C. The effect of propylene glycol was examined in more detail and revealed that even at concentrations too low to prevent freezing at -10 degrees C, -20 degrees C, and -80 degrees C, damage to the vaccine could be prevented. A pilot study using two commercially available diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccines suggested that the same stabilizers might protect these vaccines from freeze-thaw agglomeration as well. It remains to be determined if preventing agglomeration of DTaP vaccines preserves their antigenic activity following freeze-thaw events.

Methods for addressing "innocent bystanders" when evaluating safety of concomitant vaccines.

PubMed

Wang, Shirley V; Abdurrob, Abdurrahman; Spoendlin, Julia; Lewis, Edwin; Newcomer, Sophia R; Fireman, Bruce; Daley, Matthew F; Glanz, Jason M; Duffy, Jonathan; Weintraub, Eric S; Kulldorff, Martin

2018-04-01

The need to develop methods for studying the safety of childhood immunization schedules has been recognized by the Institute of Medicine and Department of Health and Human Services. The recommended childhood immunization schedule includes multiple vaccines in a visit. A key concern is safety of concomitant (same day) versus separate day vaccination. This paper addresses a methodological challenge for observational studies using a self-controlled design to investigate the safety of concomitant vaccination. We propose a process for distinguishing which of several concomitantly administered vaccines is responsible for increased risk of an adverse event while adjusting for confounding due to relationships between effect modifying risk factors and concomitant vaccine combinations. We illustrate the approach by re-examining the known increase in risk of seizure 7 to 10 days after measles-mumps-rubella (MMR) vaccination and evaluating potential independent or modifying effects of other vaccines. Initial analyses suggested that DTaP had both an independent and potentiating effect on seizure. After accounting for the relationship between age at vaccination and vaccine combination, there was little evidence for increased risk of seizure with same day administration of DTaP and MMR; incidence rate ratio, 95% confidence interval 1.2 (0.9-1.6), P value = θ.226. We have shown that when using a self-controlled design to investigate safety of concomitant vaccination, it can be critically important to adjust for time-invariant effect modifying risk factors, such as age at time of vaccination, which are structurally related to vaccination patterns due to recommended immunization schedules. Copyright © 2018 John Wiley & Sons, Ltd.

Coverage with Tetanus, Diphtheria, and Acellular Pertussis Vaccine and Influenza Vaccine Among Pregnant Women - Minnesota, March 2013-December 2014.

PubMed

Barber, Alexandra; Muscoplat, Miriam Halstead; Fedorowicz, Anna

2017-01-20

Pertussis and influenza infections can result in severe disease in infants. The diphtheria, tetanus, acellular pertussis (DTaP) vaccine is recommended for infants beginning at age 2 months, and influenza vaccine is recommended for infants aged ≥6 months. Vaccination of pregnant women induces the production of antibodies that are transferred across the placenta to the fetus and provide passive protection until infants are old enough to receive DTaP and influenza vaccines (1-3). To protect young infants before they are age-eligible for vaccination, the Advisory Committee on Immunization Practices (ACIP) has recommended since 2004 that all women who are or will be pregnant during influenza season receive inactivated influenza vaccine (1), and since 2013 that all pregnant women receive the tetanus, diphtheria, acellular pertussis (Tdap) vaccine (3). Tdap and influenza vaccination coverage was assessed among pregnant women in Minnesota. Vital records data containing maternal demographic characteristics, prenatal care data, and delivery payment methods were matched with vaccination data from the Minnesota Immunization Information Connection (MIIC) to assess vaccination coverage. MIIC stores vaccination records for Minnesota residents. Overall, coverage with Tdap vaccine was 58.2% and with influenza vaccine was 45.9%. Coverage was higher for each vaccine among women who received adequate prenatal care compared with those who received inadequate or intermediate care, based on the initiation of prenatal care and the number of recommended prenatal visits attended. Coverage also varied based on mother's race, country of birth or region, and other demographic characteristics. Further study is needed to better understand the maternal vaccination disparities found in this study and to inform future public health initiatives.

Immunogenicity study to investigate the interchangeability among three different types of polio vaccine: A cohort study in Japan.

PubMed

Ohfuji, Satoko; Ito, Kazuya; Ishibashi, Motoki; Shindo, Shizuo; Takasaki, Yoshio; Yokoyama, Takashi; Yokoyama, Takato; Yamashita, Yuji; Shibao, Keigo; Nakano, Takashi; Tsuru, Tomomi; Irie, Shin; Hirota, Yoshio

2017-06-01

In Japan, the routine immunization program with oral polio vaccine (OPV) has been suspended since September 2012, when a program with 4 doses of inactivated monovalent polio vaccine (IPV) or quadrivalent vaccine against diphtheria, pertussis, and tetanus with IPV (DTaP-IPV) was introduced. The aim of this study was to examine the interchangeability among these 3 types of polio vaccines.We conducted a prospective cohort study at 5 pediatric clinics in Japan. A total of 153 infants were assigned to 1 of the 4 groups by considering the vaccination history of OPV and trivalent vaccine against DTaP. Eleven infants with a history of OPV received 3 doses of DTaP-IPV; 49 infants with a history of OPV and DTaP received 3 doses of IPV; 50 polio vaccine-naïve infants received 2 doses of IPV followed by 2 doses of DTaP-IPV; and 43 polio vaccine-naive infants received 2 doses of DTaP-IPV followed by IPV. The immunogenicity after polio vaccination was evaluated among these 4 groups.After 2 doses of polio vaccination, more than 80% of the infants exhibited a neutralization antibody titer ≥1:8 for all Sabin strains and wild strains in all groups. After the third dose, the seroprotection proportion (i.e., a neutralization antibody titer ≥1:8) reached about 100%. After the fourth dose, a neutralization antibody titer exceeded the required protective levels (i.e., a neutralization antibody titer ≥1:8) considerably in all groups.Four doses of polio vaccines induced a sufficient level of immunity in Japanese infants, irrespective of vaccine combinations or order.

Vaccination coverage among children in kindergarten - United States, 2013-14 school year.

PubMed

Seither, Ranee; Masalovich, Svetlana; Knighton, Cynthia L; Mellerson, Jenelle; Singleton, James A; Greby, Stacie M

2014-10-17

State and local vaccination requirements for school entry are implemented to maintain high vaccination coverage and protect schoolchildren from vaccine-preventable diseases. Each year, to assess state and national vaccination coverage and exemption levels among kindergartners, CDC analyzes school vaccination data collected by federally funded state, local, and territorial immunization programs. This report describes vaccination coverage in 49 states and the District of Columbia (DC) and vaccination exemption rates in 46 states and DC for children enrolled in kindergarten during the 2013-14 school year. Median vaccination coverage was 94.7% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.0% for varying local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccine; and 93.3% for 2 doses of varicella vaccine among those states with a 2-dose requirement. The median total exemption rate was 1.8%. High exemption levels and suboptimal vaccination coverage leave children vulnerable to vaccine-preventable diseases. Although vaccination coverage among kindergartners for the majority of reporting states was at or near the 95% national Healthy People 2020 targets for 4 doses of DTaP, 2 doses of MMR, and 2 doses of varicella vaccine, low vaccination coverage and high exemption levels can cluster within communities. Immunization programs might have access to school vaccination coverage and exemption rates at a local level for counties, school districts, or schools that can identify areas where children are more vulnerable to vaccine-preventable diseases. Health promotion efforts in these local areas can be used to help parents understand the risks for vaccine-preventable diseases and the protection that vaccinations provide to their children.

Does closure of children's medical home impact their immunization coverage?

PubMed

Kolasa, M S; Stevenson, J; Ossa, A; Lutz, J

2014-12-01

Little is known about the impact closing a health care facility has on immunization coverage of children utilizing that facility as a medical home. The authors assessed the impact of closing a Medicaid managed care facility in Philadelphia on immunization coverage of children, primarily low income children from racial/ethnic minority groups, utilizing that facility for routine immunizations. Observational longitudinal cohort case study. Eligible children were born 03/01/05-06/30/07, present in Philadelphia's immunization information system (IIS), and were active clients of the facility before it closed in September 2007. IIS-recorded immunization coverage at ages 5, 7, 13, 16 and 19 months through January 2009 was compared between clinic children age-eligible to receive specific vaccines before clinic closing (preclosure cohorts) and children not age-eligible to receive those vaccines prior to closing (postclosure cohorts). Of 630 eligible children, 99 (16%) had no additional IIS-recorded immunizations. Third dose DTaP vaccine coverage at age seven months among preclosure cohorts was 54.4% vs. 40.3% among postclosure cohorts [risk ratio 1.31 (1.15,1.49)]. Fourth dose DTaP coverage at 19 months was 65.9% vs. 57.7% [risk ratio 1.24 (1.08,1.42)]. MMR coverage at 16 months was 79.5% vs. 69.9% [risk ratio 1.47 (1.22, 1.76)]. Coverage for the 431331 vaccination series at 19 months was 63.8% vs. 53.8% [risk ratio 1.28 (1.12,1.88)]. Immunization coverage declined at key age milestones for active clients of a Medicaid managed care that closed as compared with preclosure cohorts of clients from the same facility. When a primary health care facility closes, efforts should be made to ensure that children who had received vaccinations at that facility quickly establish a new medical home. Published by Elsevier Ltd.

Immunogenicity and safety of a second booster dose of an acellular pertussis vaccine combined with reduced antigen content diphtheria-tetanus toxoids 10 years after a first booster in adolescence: An open, phase III, non-randomized, multi-center study.

PubMed

Kovac, Martina; Kostanyan, Lusiné; Mesaros, Narcisa; Kuriyakose, Sherine; Varman, Meera

2018-04-09

Pertussis is a highly contagious disease, for which periodic peaks in incidence and an increasing number of outbreaks have been observed over the last decades. The reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine (Tdap) can be used to boost individuals aged ≥10 years, vaccinated in infancy with a diphtheria-tetanus-acellular pertussis vaccine (DTaP), to reduce pertussis morbidity and maintain protection against diphtheria and tetanus throughout adolescence and adulthood. This phase III, open-label, non-randomized, multicenter follow-up study (NCT01738477) enrolled 19-30-year-old participants from the United States who had received booster vaccination 10 years earlier with either Tdap (Tdap group) or Td (Td group). In total, 128 (Tdap group) and 37 (Td group) participants received Tdap vaccination. After administration of Tdap, all participants were seroprotected (antibody concentrations ≥0.1 international units [IU]/ml) against diphtheria and tetanus. Immune responses to a second Tdap dose in the Tdap group were shown to be non-inferior to responses elicited by a first Tdap dose in the Td group for diphtheria and tetanus and to a 3-dose DTaP vaccination during infancy for pertussis antigens (primary objectives). Post-booster vaccination, all participants in both groups had antibody concentrations above assay cut-offs and antibody geometric mean concentrations increased by 3.8-15.5-fold compared to pre-booster levels for all antigens. The incidence of adverse events was similar in the Td (80.6%) and Tdap (85.6%) groups (no serious adverse events reported). A Tdap dose administered after previous Td or Tdap vaccination was shown to be immunogenic and well-tolerated in young adults, supporting repeated vaccination with Tdap at 10-year intervals.

Characterization of Vaccination Policies for Attendance and Employment at Day/Summer Camps in New York State.

PubMed

Prescott, William A; Violanti, Kelsey C; Fusco, Nicholas M

2018-01-01

New York state requires day/summer camps to keep immunization records for all enrolled campers and strongly recommends requiring vaccination for all campers and staff. The objective of this study was to characterize immunization requirements/recommendations for children/adolescents enrolled in and staff employed at day/summer camps in New York state. An electronic hyperlink to a 9-question survey instrument was distributed via e-mail to 178 day/summer camps located in New York state cities with a population size greater than 100 000 people. A follow-up telephone survey was offered to nonresponders. The survey instrument included questions pertaining to vaccination documentation policies for campers/staff and the specific vaccines that the camp required/recommended. Fisher's exact and Chi-square tests were used to analyze categorical data. Sixty-five day/summer camps responded to the survey (36.5% response rate): 48 (73.8%) and 23 (41.8%) camps indicated having a policy/procedure for documenting vaccinations for campers and staff, respectively. Camps that had a policy/procedure for campers were more likely to have a policy/procedure for staff ( P = .0007). Age-appropriate vaccinations that were required/recommended for campers by at least 80% of camps included: measles, mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTaP), hepatitis B, inactivated/oral poliovirus (IPV/OPV), Haemophilus influenzae type b (Hib), and varicella. Age-appropriate vaccinations that were required/recommended for staff by at least 80% of camps included: DTaP, hepatitis B, IPV/OPV, MMR, meningococcus, varicella, Hib, and tetanus, diphtheria, and pertussis (Tdap). Vaccination policies at day/summer camps in New York state appear to be suboptimal. Educational outreach may encourage camps to strengthen their immunization policies, which may reduce the transmission of vaccine-preventable diseases.

Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years.

PubMed

Carlsson, R M; Gustafsson, L; Hallander, H O; Ljungman, M; Olin, P; Gothefors, L; Nilsson, L; Netterlid, E

2015-07-17

Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20μg) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5μg). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. The adolescent study was registered at ClinicalTrials.gov on 26 March 2009 (NCT00870350). Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunogenicity of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria, tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study.

PubMed

John, T; Voysey, M; Yu, L M; McCarthy, N; Baudin, M; Richard, P; Fiquet, A; Kitchin, N; Pollard, A J

2015-08-26

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hib antibody responses in infants following diphtheria, tetanus, acellular pertussis, and conjugated Haemophilus influenzae type b (Hib) combination vaccines with decreasing amounts of tetanus toxoid.

PubMed

Bernstein, Henry H; Seyferth, Elisabeth R

2017-12-04

While combination vaccines have contributed to improved vaccine uptake rates in children, studies have documented varied immunogenicity to specific vaccine components. We studied whether varying the amount of tetanus toxoid (TT) in a DTaP and Hib combination vaccine would result in immunogenicity comparable with separate, concurrent administration. We evaluated the immunogenicity of Massachusetts Biologic Laboratories (MBL) diphtheria, tetanus, and acellular pertussis (mDTaP) vaccine combined with tetanus-conjugated MBL Haemophilus influenzae type b vaccine (mHib) in a single injection (DTaPH). We compared four DTaPH vaccines containing varying concentrations of TT. We also evaluated the immune response to the DTaP vaccine manufactured by Connaught Laboratories (now known as Sanofi Pasteur) given with mHib and with Wyeth Hib-CRM 197 (HbOC) as separate injections. Vaccines were administered to 240 healthy infants at 2, 4, and 6 months of age, and blood specimens for antibody determination were obtained before each immunization and one month after the third immunization. We found no significant differences in immune response to the vaccines between the four DTaPH groups. Hib antibody responses were similar in the mHib and the HbOC groups but significantly lower in the DTaPH groups, as measured by Chinese Hamster Ovary (CHO) cell neutralization titers and filamentous hemagglutinin antigen (FHA) geometric mean concentrations (GMC) of anti-Hib antibodies. There were no significant differences between the groups in pertussis or tetanus toxoid antibody levels. Reducing tetanus toxoid amounts did not produce comparable immunogenicity for Hib. The nature of the interaction between immune responses to DTaPH components should be explored further to enable the development of better Hib-containing combination vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

PubMed

Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

2008-08-18

CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2017-18 Influenza Season.

PubMed

Grohskopf, Lisa A; Sokolow, Leslie Z; Broder, Karen R; Walter, Emmanuel B; Bresee, Joseph S; Fry, Alicia M; Jernigan, Daniel B

2017-08-25

, Connecticut); and expansion of the age indication for FluLaval Quadrivalent (IIV4; ID Biomedical Corporation of Quebec, Quebec City, Quebec, Canada), previously licensed for ≥3 years, to ≥6 months.• Pregnant women may receive any licensed, recommended, age-appropriate influenza vaccine.• Afluria (IIV3; Seqirus, Parkville, Victoria, Australia) may be used for persons aged ≥5 years, consistent with Food and Drug Administration-approved labeling.• FluMist Quadrivalent (LAIV4; MedImmune, Gaithersburg, Maryland) should not be used during the 2017-18 season due to concerns about its effectiveness against influenza A(H1N1)pdm09 viruses in the United States during the 2013-14 and 2015-16 influenza seasons.This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2017-18 season in the United States. A Background Document containing further information and a summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to licensed influenza vaccines used within Food and Drug Administration-licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC's influenza website periodically for additional information.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2017–18 Influenza Season

PubMed Central

Sokolow, Leslie Z.; Broder, Karen R.; Walter, Emmanuel B.; Bresee, Joseph S.; Fry, Alicia M.; Jernigan, Daniel B.

2017-01-01

; Protein Sciences, Meriden, Connecticut); and expansion of the age indication for FluLaval Quadrivalent (IIV4; ID Biomedical Corporation of Quebec, Quebec City, Quebec, Canada), previously licensed for ≥3 years, to ≥6 months. • Pregnant women may receive any licensed, recommended, age-appropriate influenza vaccine. • Afluria (IIV3; Seqirus, Parkville, Victoria, Australia) may be used for persons aged ≥5 years, consistent with Food and Drug Administration–approved labeling. • FluMist Quadrivalent (LAIV4; MedImmune, Gaithersburg, Maryland) should not be used during the 2017–18 season due to concerns about its effectiveness against influenza A(H1N1)pdm09 viruses in the United States during the 2013–14 and 2015–16 influenza seasons. This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2017–18 season in the United States. A Background Document containing further information and a summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to licensed influenza vaccines used within Food and Drug Administration–licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC’s influenza website periodically for additional information. PMID:28841201

National, State, and Selected Local Area Vaccination Coverage Among Children Aged 19-35 Months - United States, 2014.

PubMed

Hill, Holly A; Elam-Evans, Laurie D; Yankey, David; Singleton, James A; Kolasa, Maureen

2015-08-28

The reduction in morbidity and mortality associated with vaccine-preventable diseases in the United States has been described as one of the 10 greatest public health achievements of the first decade of the 21st century. A recent analysis concluded that routine childhood vaccination will prevent 322 million cases of disease and about 732,000 early deaths among children born during 1994-2013, for a net societal cost savings of $1.38 trillion. The National Immunization Survey (NIS) has monitored vaccination coverage among U.S. children aged 19-35 months since 1994. This report presents national, regional, state, and selected local area vaccination coverage estimates for children born from January 2011 through May 2013, based on data from the 2014 NIS. For most vaccinations, there was no significant change in coverage between 2013 and 2014. The exception was hepatitis A vaccine (HepA), for which increases were observed in coverage with both ≥1 and ≥2 doses. As in previous years, <1% of children received no vaccinations. National coverage estimates indicate that the Healthy People 2020 target* of 90% was met for ≥3 doses of poliovirus vaccine (93.3%), ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.5%), ≥3 doses of hepatitis B vaccine (HepB) (91.6%), and ≥1 dose of varicella vaccine (91.0%). Coverage was below target for ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine (DTaP), the full series of Haemophilus influenzae type b (Hib) vaccine, hepatitis B (HepB) birth dose,† ≥4 doses pneumococcal conjugate vaccine (PCV), ≥2 doses of HepA, the full series of rotavirus vaccine, and the combined vaccine series.§ Examination of coverage by child's race/ethnicity revealed lower estimated coverage among non-Hispanic black children compared with non-Hispanic white children for several vaccinations, including DTaP, the full series of Hib, PCV, rotavirus vaccine, and the combined series. Children from households classified as below the

Assessment of safety and efficacy against Bordetella pertussis of a new tetanus-reduced dose diphtheria-acellular pertussis vaccine in a murine model.

PubMed

Kwon, Hyo Jin; Han, Seung Beom; Kim, Bo Ram; Kang, Kyu Ri; Huh, Dong Ho; Choi, Gi Sub; Ahn, Dong Ho; Kang, Jin Han

2017-04-04

Tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccination during adolescence was introduced in response to the resurgence of pertussis in various countries. A new Tdap vaccine was manufactured in Korea as a countermeasure against a predicted Tdap vaccine shortage. This study was performed to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model. Four-week-old BABL/c mice were used for assessment of immunogenicity and protection efficacy. A single dose of primary diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered, followed by a single dose of Tdap booster vaccine after a 12-week interval. Anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), and anti-pertactin (PRN) IgG titers were measured before primary vaccination, and before and after booster vaccination. An intranasal challenge test was performed after booster vaccination to determine protection efficacy. To assess safety, mouse weight gain test and leukocytosis promotion test were performed using 4-week-old ddY female mice. Anti-PT and anti-FHA IgG titers after booster vaccination were significantly higher than those before booster vaccination with either the new vaccine or a commercially available Tdap vaccine (P = 0.01 for all occasions). After booster vaccination, no significant difference was observed between the two vaccines in antibody titers against pertussis antigens (P = 0.53 for anti-PT IgG, P = 0.91 for anti-FHA IgG, P = 0.39 for anti-PRN IgG). In the intranasal challenge test, inoculated B. pertussis was eradicated 7 days after infection. On days 4 and 7 after infection, colony counts of B. pertussis were not significantly different between the new and positive control vaccine groups (P = 1.00). Mean body weight changes and leukocyte counts of the new vaccine, positive control, and negative control groups were not significantly different 7 days after vaccination (P�

Crossing the Bridge: An Evaluation of the Drug Treatment Alternative-to-Prison (DTAP) Program. A CASA White Paper.

ERIC Educational Resources Information Center

Columbia Univ., New York, NY. National Center on Addiction and Substance Abuse.

Previous research has found that 80 percent of all adults incarcerated for felonies either had regularly used illegal drugs or abused alcohol, been convicted of a drug or alcohol violation, were under the influence of drugs and/or alcohol at the time of their crime, committed a crime to support their habit, or exhibited some combination of these…

Dynamic profiles of neutralizing antibody responses elicited in rhesus monkeys immunized with a combined tetravalent DTaP-Sabin IPV candidate vaccine.

PubMed

Sun, Mingbo; Ma, Yan; Xu, Yinhua; Yang, Huijuan; Shi, Li; Che, Yanchun; Liao, Guoyang; Jiang, Shude; Zhang, Shumin; Li, Qihan

2014-02-19

The World Health Organization has recommended that a Sabin inactivated polio vaccine (IPV) should gradually and synchronously replace oral polio vaccines for routine immunizations because its benefits in eliminating vaccine-associated paralytic poliomyelitis have been reported in different phases of clinical trials. It is also considered important to explore new tetravalent diphtheria, tetanus, and acellular pertussis-Sabin IPV (DTaP-sIPV) candidate vaccines for possible use in developing countries. In this study, the immunogenicity of a combined tetravalent DTaP-sIPV candidate vaccine was investigated in primates by evaluating the neutralizing antibody responses it induced. The dynamic profiles of the antibody responses to each of the separate antigenic components and serotypes of Sabin IPV were determined and their corresponding geometric mean titers were similar to those generated by the tetravalent diphtheria, tetanus, and acellular pertussis-conventional IPV (DTaP-cIPV), the tetravalent diphtheria, tetanus, and acellular pertussis (DTaP), and Sabin IPV vaccines in the control groups. This implies that protective immunogenic effects are conferred by this combined tetravalent formulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP)

PubMed Central

Tiwari, Tejpratap; Moro, Pedro; Messonnier, Nancy E.; Reingold, Arthur; Sawyer, Mark; Clark, Thomas A.

2018-01-01

Summary This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus, diphtheria, and pertussis in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations and replaces all previously published reports and policy notes; it is intended for use by clinicians and public health providers as a resource. ACIP recommends routine vaccination for tetanus, diphtheria, and pertussis. Infants and young children are recommended to receive a 5-dose series of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccines, with one adolescent booster dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Adults who have never received Tdap also are recommended to receive a booster dose of Tdap. Women are recommended to receive a dose of Tdap during each pregnancy, which should be administered from 27 through 36 weeks’ gestation, regardless of previous receipt of Tdap. After receipt of Tdap, adolescents and adults are recommended to receive a booster tetanus and diphtheria toxoids (Td) vaccine every 10 years to assure ongoing protection against tetanus and diphtheria. PMID:29702631

Additional recommendations for use of tetanus toxoid, reduced-content diphtheria toxoid, and acellular pertussis vaccine (Tdap).

PubMed

2011-10-01

The American Academy of Pediatrics and the Centers for Disease Control and Prevention are amending previous recommendations and making additional recommendations for the use of tetanus toxoid, reduced-content diphtheria toxoid, and acellular pertussis vaccine (Tdap). Review of the results from clinical trials and other studies has revealed no excess reactogenicity when Tdap is given within a short interval after other tetanus- or diphtheria-containing toxoid products, and accrual of postmarketing adverse-events reports reveals an excellent safety record for Tdap. Thus, the recommendation for caution regarding Tdap use within any interval after a tetanus- or diphtheria-containing toxoid product is removed. Tdap should be given when it is indicated and when no contraindication exists. In further efforts to protect people who are susceptible to pertussis, the American Academy of Pediatrics and Centers for Disease Control and Prevention recommend a single dose of Tdap for children 7 through 10 years of age who were underimmunized with diphtheria-tetanus-acellular pertussis (DTaP). Also, the age for recommendation for Tdap is extended to those aged 65 years and older who have or are likely to have contact with an infant younger than 12 months (eg, health care personnel, grandparents, and other caregivers).

Risk factors for adverse events after vaccinations performed during the initial hospitalization of infants born prematurely.

PubMed

Wilińska, Maria; Warakomska, Małgorzata; Głuszczak-Idziakowska, Ewa; Jackowska, Teresa

There are significant delays in implementing vaccination among preterm infants. Description of the frequency and kinds of adverse events following immunization in preterms. Establishment of the group of preterms who will distinctively be susceptible to adverse events. Demographical, clinical data and the occurrence of adverse events after DTaP, HIB and pneumococcal vaccination among preterms during their initial hospitalization were prospectively collected with the use of an electronic data form between 1st June 2011 and 31st May 2015. The analysis was conducted on 138 patients. The groups were divided according to maturity (I: ≤ GA 28w n=73 and GA 29-36 w n=65). There were no statistically significant differences between the groups in the occurrence of adverse events. Out of the total group, following vaccination apnoea developed in 6 newborns (4%) and activity dysfunctions were observed in 13 newborns (10%). The occurrence of apnoea after vaccination positively correlated with the time of non-invasive ventilation and the occurrence of late infection. There were no statistically significant demographical or clinical risk factors for the development of activity dysfunctions following vaccination. Term vaccination in clinically stable preterm infants is a safe medical procedure. However, long-term non-invasive respiratory support and late infections are risk factors for apnea following vaccinations. In these patients vaccinations should be considered during hospitalization.

Definition of Human Epitopes Recognized in Tetanus Toxoid and Development of an Assay Strategy to Detect Ex Vivo Tetanus CD4+ T Cell Responses

PubMed Central

da Silva Antunes, Ricardo; Paul, Sinu; Sidney, John; Weiskopf, Daniela; Dan, Jennifer M.; Phillips, Elizabeth; Mallal, Simon; Crotty, Shane; Sette, Alessandro; Lindestam Arlehamn, Cecilia S.

2017-01-01

Despite widespread uses of tetanus toxoid (TT) as a vaccine, model antigen and protein carrier, TT epitopes have been poorly characterized. Herein we defined the human CD4+ T cell epitope repertoire by reevaluation of previously described epitopes and evaluation of those derived from prediction of HLA Class II binding. Forty-seven epitopes were identified following in vitro TT stimulation, with 28 epitopes accounting for 90% of the total response. Despite this diverse range of epitopes, individual responses were associated with only a few immunodominant epitopes, with each donor responding on average to 3 epitopes. For the top 14 epitopes, HLA restriction could be inferred based on HLA typing of the responding donors. HLA binding predictions re-identified the vast majority of known epitopes, and identified 24 additional novel epitopes. With these epitopes, we created a TT epitope pool, which allowed us to characterize TT responses directly ex vivo using a cytokine-independent Activation Induced Marker (AIM) assay. These TT responses were highly Th1 or Th2 polarized, which was dependent upon the original priming vaccine, either the cellular DTwP or acellular DTaP formulation. This polarization remained despite the original priming having occurred decades past and a recent booster immunization with a reduced acellular vaccine formulation. While TT responses following booster vaccination were not durably increased in magnitude, they were associated with a relative expansion of CD4+ effector memory T cells. PMID:28081174

Definition of Human Epitopes Recognized in Tetanus Toxoid and Development of an Assay Strategy to Detect Ex Vivo Tetanus CD4+ T Cell Responses.

PubMed

da Silva Antunes, Ricardo; Paul, Sinu; Sidney, John; Weiskopf, Daniela; Dan, Jennifer M; Phillips, Elizabeth; Mallal, Simon; Crotty, Shane; Sette, Alessandro; Lindestam Arlehamn, Cecilia S

2017-01-01

Despite widespread uses of tetanus toxoid (TT) as a vaccine, model antigen and protein carrier, TT epitopes have been poorly characterized. Herein we defined the human CD4+ T cell epitope repertoire by reevaluation of previously described epitopes and evaluation of those derived from prediction of HLA Class II binding. Forty-seven epitopes were identified following in vitro TT stimulation, with 28 epitopes accounting for 90% of the total response. Despite this diverse range of epitopes, individual responses were associated with only a few immunodominant epitopes, with each donor responding on average to 3 epitopes. For the top 14 epitopes, HLA restriction could be inferred based on HLA typing of the responding donors. HLA binding predictions re-identified the vast majority of known epitopes, and identified 24 additional novel epitopes. With these epitopes, we created a TT epitope pool, which allowed us to characterize TT responses directly ex vivo using a cytokine-independent Activation Induced Marker (AIM) assay. These TT responses were highly Th1 or Th2 polarized, which was dependent upon the original priming vaccine, either the cellular DTwP or acellular DTaP formulation. This polarization remained despite the original priming having occurred decades past and a recent booster immunization with a reduced acellular vaccine formulation. While TT responses following booster vaccination were not durably increased in magnitude, they were associated with a relative expansion of CD4+ effector memory T cells.

Safety and Immunogenicity of Tetanus-Diphtheria-Acellular Pertussis Vaccine Administered to Children 10 or 11 Years of Age

PubMed Central

Pool, Vitali; Greenberg, David P.; Johnson, David R.; Sheng, Xiaohua; Decker, Michael D.

2014-01-01

Boosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.) PMID:25230939

Mothers' preferences regarding new combination vaccines for their children in Japan, 2014.

PubMed

Shono, Aiko; Kondo, Masahide

2017-04-03

A number of new vaccines to prevent childhood diseases have been introduced globally over the last few decades. Only four combination vaccines are currently available in Japan, DTaP/sIPV, DTaP, DT, and MR, leading to complex infant vaccine scheduling. This study aims to investigate mothers' preferences with respect to combination vaccines for their children, should new combination vaccines become available that have not yet been launched in Japan or that will be developed in the future. We conducted a web-based, cross-sectional survey of 1,243 mothers who had at least one child between 2 months and 3 y of age. Mothers were recruited from an online survey panel of registered users. Their preferences were elicited using discrete choice experiments, the analyzed main effects model, and interactions using a mixed logit model. Mothers showed a preference for vaccines that prevented multiple diseases, had fewer injections per doctor visit, lower price, and lower risk of adverse events. Respondents valued a reduced risk of adverse events the most among all attributes in this study. The estimated monetary value of the willingness to pay for a 1% reduction in the risk of adverse events was ¥ 92,557 ($ 907). Therefore, if new combination vaccines are introduced, the risk of adverse events after vaccination is an especially important factor for mothers. While the safety of the vaccines themselves is required, health professionals should also inform mothers about the benefits and risks of vaccination, to allay mothers' concerns about vaccine safety.

Vaccination Coverage Disparities Between Foreign-Born and U.S.-Born Children Aged 19-35 Months, United States, 2010-2012.

PubMed

Varan, Aiden K; Rodriguez-Lainz, Alfonso; Hill, Holly A; Elam-Evans, Laurie D; Yankey, David; Li, Qian

2017-08-01

Healthy People 2020 targets high vaccination coverage among children. Although reductions in coverage disparities by race/ethnicity have been described, data by nativity are limited. The National Immunization Survey is a random-digit-dialed telephone survey that estimates vaccination coverage among U.S. children aged 19-35 months. We assessed coverage among 52,441 children from pooled 2010-2012 data for individual vaccines and the combined 4:3:1:3*:3:1:4 series (which includes ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine/diphtheria and tetanus toxoids vaccine/diphtheria, tetanus toxoids, and pertussis vaccine, ≥3 doses of poliovirus vaccine, ≥1 dose of measles-containing vaccine, ≥3 or ≥4 doses of Haemophilus influenzae type b vaccine (depending on product type of vaccine; denoted as 3* in the series name), ≥3 doses of hepatitis B vaccine, ≥1 dose of varicella vaccine, and ≥4 doses of pneumococcal conjugate vaccine). Coverage estimates controlling for sociodemographic factors and multivariable logistic regression modeling for 4:3:1:3*:3:1:4 series completion are presented. Significantly lower coverage among foreign-born children was detected for DTaP, hepatitis A, hepatitis B, Hib, pneumococcal conjugate, and rotavirus vaccines, and for the combined series. Series completion disparities persisted after control for demographic, access-to-care, poverty, and language effects. Substantial and potentially widening disparities in vaccination coverage exist among foreign-born children. Improved immunization strategies targeting this population and continued vaccination coverage monitoring by nativity are needed.

Vaccination coverage among children in kindergarten - United States, 2012-13 school year.

PubMed

2013-08-02

State and local school vaccination requirements are implemented to maintain high vaccination coverage and minimize the risk from vaccine preventable diseases. To assess school vaccination coverage and exemptions, CDC annually analyzes school vaccination coverage data from federally funded immunization programs. These awardees include 50 states and the District of Columbia (DC), five cities, and eight U.S.-affiliated jurisdictions. This report summarizes vaccination coverage from 48 states and DC and exemption rates from 49 states and DC for children entering kindergarten for the 2012-13 school year. Forty-eight states and DC reported vaccination coverage, with medians of 94.5% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.1% for local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccination; and 93.8% for 2 doses of varicella vaccine among awardees with a 2-dose requirement. Forty-nine states and DC reported exemption rates, with the median total of 1.8%. Although school entry coverage for most awardees was at or near national Healthy People 2020 targets of maintaining 95% vaccination coverage levels for 2 doses of MMR vaccine, 4 doses of DTaP† vaccine, and 2 doses of varicella vaccine, low vaccination and high exemption levels can cluster within communities, increasing the risk for disease. Reports to CDC are aggregated at the state level; however, local reporting of school vaccination coverage might be accessible by awardees. These local-level data can be used to create evidence-based health communication strategies to help parents understand the risks for vaccine-preventable diseases and the benefits of vaccinations to the health of their children and other kindergarteners.

Vaccination of adults 65 years of age and older with tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Boostrix(®)): results of two randomized trials.

PubMed

Weston, Wayde M; Friedland, Leonard R; Wu, Xiangfeng; Howe, Barbara

2012-02-21

Pertussis can cause significant morbidity in elderly patients, who can also transmit this disease to infants and young children. There is little data available on the use of acellular pertussis vaccines in recipients ≥65 years of age. Two studies examined the safety and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine (Boostrix(®)) in healthy ≥65 year olds. In Study A subjects received single doses of Tdap and seasonal influenza vaccine either co-administered or given one month apart. In Study B subjects received either Tdap or tetanus-diphtheria (Td) vaccine. Antibodies were measured before and one month after vaccination. Reactogenicity and safety were actively assessed using diary cards. A total of 1104 subjects 65 years of age and older received a Tdap vaccination in the two studies. In study A, no differences in immune responses to Tdap or influenza vaccine were observed between co-administered or sequentially administered vaccines. In study B, Tdap was non-inferior to Td with respect to diphtheria and tetanus seroprotection, and anti-pertussis GMCs were non-inferior to those observed in infants following a 3-dose diphtheria, tetanus and acellular pertussis (DTaP) primary vaccination series, in whom efficacy against pertussis was demonstrated. Reports of adverse events were similar between Tdap and Td groups. Tdap was found to be immunogenic in subjects ≥65 years, with a safety profile comparable to US-licensed Td vaccine. Tdap and influenza vaccine may be co-administered without compromise of either the reactogenicity or immunogenicity profiles of the two vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Safety and immunogenicity of tetanus-diphtheria-acellular pertussis vaccine administered to children 10 or 11 years of age.

PubMed

Marshall, Gary S; Pool, Vitali; Greenberg, David P; Johnson, David R; Sheng, Xiaohua; Decker, Michael D

2014-11-01

Boosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Improving Immunization Rates Through Community-Based Participatory Research: Community Health Improvement for Milwaukee’s Children Program

PubMed Central

Willis, Earnestine; Sabnis, Svapna; Hamilton, Chelsea; Xiong, Fue; Coleman, Keli; Dellinger, Matt; Watts, Michelle; Cox, Richard; Harrell, Janice; Smith, Dorothy; Nugent, Melodee; Simpson, Pippa

2016-01-01

Background Nationally, immunization coverage for the DTaP/3HPV/1MMR/3HepB/3Hib/1VZV antigen series in children ages 19–35 months are near or above the Healthy People 2020 target (80%). However, children in lower socioeconomic families experience lower coverage rates. Objective Using a community-based participatory research (CBPR) approach, Community Health Improvement for Milwaukee Children (CHIMC) intervened to reduce disparities in childhood immunizations. Methods The CHIMC adopted a self-assessment to examine the effectiveness of adhering to CBPR principles. Using behavior change models, CHIMC implemented education, social marketing campaign, and theory of planned behavior interventions. Community residents and organizational representatives vetted all processes, messages, and data collection tools. Results Adherence to the principles of CBPR was consistently positive over the 8-year period. CHIMC enrolled 565 parents/caregivers with 1,533 children into educational and planned behavior change (PBC) interventions, and enrolled another 406 surveyed for the social marketing campaign. Retention rate was high (80%) with participants being predominately Black females (90%) and the unemployed (64%); children’s median age was 6.2 years. Increased knowledge about immunizations was consistently observed among parents/caregivers. Social marketing data revealed high recognition (85%) of the community-developed message (“Take Control: Protect Your Child with Immunizations”). Barriers and facilitators to immunize children revealed protective factors positively correlated with up-to-date (UTD) status (p < 0.007). Ultimately, children between the ages of 19 and 35 months whose parents/caregivers completed education sessions and benefitted from a community-wide social marketing message increased their immunization status from 45% baseline to 82% over 4 years. Conclusions Using multilayered interventions, CHIMC contributed to the elimination of immunization disparities in

Improving Immunization Rates Through Community-Based Participatory Research: Community Health Improvement for Milwaukee's Children Program.

PubMed

Willis, Earnestine; Sabnis, Svapna; Hamilton, Chelsea; Xiong, Fue; Coleman, Keli; Dellinger, Matt; Watts, Michelle; Cox, Richard; Harrell, Janice; Smith, Dorothy; Nugent, Melodee; Simpson, Pippa

2016-01-01

Nationally, immunization coverage for the DTaP/3HPV/1MMR/3HepB/3Hib/1VZV antigen series in children ages 19-35 months are near or above the Healthy People 2020 target (80%). However, children in lower socioeconomic families experience lower coverage rates. Using a community-based participatory research (CBPR) approach, Community Health Improvement for Milwaukee Children (CHIMC) intervened to reduce disparities in childhood immunizations. The CHIMC adopted a self-assessment to examine the effectiveness of adhering to CBPR principles. Using behavior change models, CHIMC implemented education, social marketing campaign, and theory of planned behavior interventions. Community residents and organizational representatives vetted all processes, messages, and data collection tools. Adherence to the principles of CBPR was consistently positive over the 8-year period. CHIMC enrolled 565 parents/caregivers with 1,533 children into educational and planned behavior change (PBC) interventions, and enrolled another 406 surveyed for the social marketing campaign. Retention rate was high (80%) with participants being predominately Black females (90%) and the unemployed (64%); children's median age was 6.2 years. Increased knowledge about immunizations was consistently observed among parents/caregivers. Social marketing data revealed high recognition (85%) of the community-developed message ("Take Control: Protect Your Child with Immunizations"). Barriers and facilitators to immunize children revealed protective factors positively correlated with up-to-date (UTD) status (p<0.007). Ultimately, children between the ages of 19 and 35 months whose parents/caregivers completed education sessions and benefitted from a community-wide social marketing message increased their immunization status from 45% baseline to 82% over 4 years. Using multilayered interventions, CHIMC contributed to the elimination of immunization disparities in children. A culturally tailored CBPR approach is effective

Lot-to-lot Consistency, Safety, Tolerability and Immunogenicity of an Investigational Hexavalent Vaccine in US Infants.

PubMed

Block, Stanley L; Klein, Nicola P; Sarpong, Kwabena; Russell, Stephen; Fling, John; Petrecz, Maria; Flores, Sheryl; Xu, Jin; Liu, Guanghan; Stek, Jon E; Foglia, Ginamarie; Lee, Andrew W

2017-02-01

This multicenter phase III study (NCT01340937) evaluated the consistency of immune responses to 3 separate lots of diphtheria-tetanus toxoids-acellular pertussis 5, inactivated poliovirus vaccine, Haemophilus influenzae type b, and hepatitis B (DTaP5-IPV-Hib-HepB), an investigational hexavalent vaccine (HV). Healthy infants were randomized (2:2:2:1) to receive HV or Pentacel (Control). Groups 1, 2 and 3 received HV at 2, 4 and 6 months, and Control at 15 months. Group 4 received Control at 2, 4, 6 and 15 months, plus Recombivax HB (HepB) at 2 and 6 months. Concomitant Prevnar 13 was given to all groups at 2, 4, 6 and 15 months; pentavalent rotavirus vaccine (RV5) was given to all groups at 2, 4 and 6 months. Blood specimens (3-5 mL) were collected immediately before administration of dose 1, postdose 3, immediately before toddler dose, and after toddler dose. Adverse events were recorded after each vaccination. The 3 manufacturing lots of HV induced consistent antibody responses to all antigens. Immunogenicity of HV was noninferior to Control for all antibodies, except for pertussis filamentous hemagglutinin geometric mean concentration postdose 3, and pertussis pertactin (PRN) geometric mean concentration after toddler dose. Postdose 3 immunogenicity of concomitantly administered Prevnar 13 was generally similar (except for serotype 6B) when given with HV or Control. Adverse events of HV were similar to Control, except for a higher rate of fever ≥38.0°C [49.2% vs. 35.4%, estimated difference 13.7% (8.4, 18.8)]. HV demonstrated lot-to-lot manufacturing consistency; safety and immunogenicity were comparable with the licensed vaccines. HV provides a new combination vaccine option within the US 2-month, 4-month and 6-month vaccine series.

[Immunisation schedule of the Spanish Association of Paediatrics: 2015 recommendations].

PubMed

Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

2015-01-01

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of current vaccines, including levels of recommendation. In our opinion, this is the optimal vaccination calendar for all children resident in Spain. Regarding the vaccines included in the official unified immunization schedule, the Committee emphasizes the administration of the first dose of hepatitis B either at birth or at 2 months of life; the recommendation of the first dose of MMR and varicella vaccine at the age of 12 months, with the second dose at the age of 2-3 years; DTaP or Tdap vaccine at the age of 6 years, followed by another Tdap booster dose at 11-12 years old; Tdap strategies for pregnant women and household contacts of the newborn, and immunization against human papillomavirus in girls aged 11-12 years old with a 2 dose scheme (0, 6 months). The Committee reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule, the same as it is being conducted in Western European countries. The recently authorised meningococcal B vaccine, currently blocked in Spain, exhibits the profile of a universal vaccine. The Committe insists on the need of having the vaccine available in communitary pharmacies. It has also proposed the free availability of varicella vaccines. Their efectiveness and safety have been confirmed when they are administred from the second year of life. Vaccination against rotavirus is recommended in all infants. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Copyright © 2014. Published by Elsevier Espana.

[Immunisation schedule of the Spanish Association of Paediatrics: 2017 recommendations].

PubMed

Moreno-Pérez, David; Álvarez García, Francisco José; Arístegui Fernández, Javier; Cilleruelo Ortega, María José; Corretger Rauet, José María; García Sánchez, Nuria; Hernández Merino, Ángel; Hernández-Sampelayo Matos, Teresa; Merino Moína, Manuel; Ortigosa Del Castillo, Luis; Ruiz-Contreras, Jesús

2017-02-01

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV- AEP) annually publishes the immunisation schedule which, in our opinion, is considered optimal for children resident in Spain, taking into account the evidence available on current vaccines. Pneumococcal and varicella immunisation in early childhood is already included in all funded vaccines present in the regional immunisation programmes. Furthermore, this committee establishes recommendations on vaccines not included in official calendars (non-funded immunisations), such as rotavirus, meningococcal B, and meningococcal ACWY. As regards funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTaP-IPV-Hib-HB) and 13-valent pneumococcal vaccines is recommended. Administration of the 6-year booster dose with DTaP is recommended, as well as a poliomyelitis dose for children who had received the 2+1 scheme, with the Tdap vaccine for adolescents and pregnant women between 27 and 32 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 12 with a two-dose scheme (0, 6 months) should be improved. Information and recommendations for male adolescents about potential beneficial effects of the tetravalent HPV vaccine should also be provided. ACWY meningococcal vaccine is the optimal choice in adolescents. For recommended unfunded immunisations, the CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish community pharmacies, with a 3+1 scheme. CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Knowledge, Attitudes and Perceptions About Routine Childhood Vaccinations Among Jewish Ultra-Orthodox Mothers Residing in Communities with Low Vaccination Coverage in the Jerusalem District.

PubMed

Stein Zamir, Chen; Israeli, Avi

2017-05-01

Background and aims Childhood vaccinations are an important component of primary prevention. Maternal and Child Health (MCH) clinics in Israel provide routine vaccinations without charge. Several vaccine-preventable-diseases outbreaks (measles, mumps) emerged in Jerusalem in the past decade. We aimed to study attitudes and knowledge on vaccinations among mothers, in communities with low immunization coverage. Methods A qualitative study including focus groups and semi-structured interviews. Results Low immunization coverage was defined below the district's mean (age 2 years, 2013) for measles-mumps-rubella-varicella 1st dose (MMR1\\MMRV1) and diphtheria-tetanus-pertussis 4th dose (DTaP4), 96 and 89%, respectively. Five communities were included, all were Jewish ultra-orthodox. The mothers' (n = 87) median age was 30 years and median number of children 4. Most mothers (94%) rated vaccinations as the main activity in the MCH clinics with overall positive attitudes. Knowledge about vaccines and vaccination schedule was inadequate. Of vaccines scheduled at ages 0-2 years (n = 13), the mean number mentioned was 3.9 ± 2.8 (median 4, range 0-9). Vaccines mentioned more often were outbreak-related (measles, mumps, polio) and HBV (given to newborns). Concerns about vaccines were obvious, trust issues and religious beliefs were not. Vaccination delay was very common and timeliness was considered insignificant. Practical difficulties in adhering to the recommended schedule prevailed. The vaccinations visits were associated with pain and stress. Overall, there was a sense of self-responsibility accompanied by inability to influence others. Conclusion Investigating maternal knowledge and attitudes on childhood vaccinations provides insights that may assist in planning tailored intervention programs aimed to increase both vaccination coverage and timeliness.

Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

NASA Astrophysics Data System (ADS)

May, J. C.; Rey, L.; Lee, Chi-Jen; Arciniega, Juan

2004-09-01

Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15-18 Months of Age in Mexico: A Randomized Trial.

PubMed

Melo, Flor Irene Rodriguez; Morales, José Juan Renteria; De Los Santos, Abiel Homero Mascareñas; Rivas, Enrique; Vigne, Claire; Noriega, Fernando

2017-06-01

The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in a number of dengue endemic countries for individuals ≥9 years of age. Before the integration of any vaccine into childhood vaccination schedules, a lack of immune interference and acceptable safety when coadministered with other recommended vaccines should be demonstrated. This randomized, multi-center phase III trial was conducted in Mexico. Healthy toddlers (n = 732) received a booster dose of a licensed pentavalent combination vaccine [diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and Haemophilus influenzae type b (DTaP-IPV//Hib)] either concomitantly or sequentially, with the second dose of CYD-TDV administered as a 3-dose schedule. Antibody titers against diphtheria toxoid, tetanus toxoid and pertussis antigens were measured by enzyme-linked immunosorbent assay. Antibodies against poliovirus and dengue serotypes were measured using a plaque reduction neutralization test. Noninferiority was demonstrated for each of the DTaP-IPV//Hib antigens if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates between the 2 groups (CYD-TDV and placebo) was ≥10%. Safety of both vaccines was assessed. Noninferiority in immune response was demonstrated for all DTaP-IPV//Hib antigens. After 3 doses of CYD-TDV, no difference was observed in the immune response for CYD-TDV between groups. There were no safety concerns during the study. Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.

Vaccination Coverage Among Children Aged 2 Years - U.S. Affiliated Pacific Islands, April-October, 2016.

PubMed

Tippins, Ashley; Murthy, Neil; Meghani, Mehreen; Solsman, Amy; Apaisam, Carter; Basilius, Merlyn; Eckert, Maribeth; Judicpa, Peter; Masunu, Yolanda; Pistotnik, Kelsey; Pedro, Daisy; Sasamoto, Jeremy; Underwood, J Michael

2018-05-25

Vaccine-preventable diseases (VPDs) cause substantial morbidity and mortality in the United States Affiliated Pacific Islands (USAPI).* CDC collaborates with USAPI immunization programs to monitor vaccination coverage. In 2016, † USAPI immunization programs and CDC piloted a method for estimating up-to-date status among children aged 2 years using medical record abstraction to ascertain regional vaccination coverage. This was the first concurrent assessment of childhood vaccination coverage across five USAPI jurisdictions (American Samoa; Chuuk State, Federated States of Micronesia [FSM]; Commonwealth of the Northern Mariana Islands [CNMI]; Republic of the Marshall Islands [RMI]; and Republic of Palau). § Differences in vaccination coverage between main and outer islands ¶ were assessed for two jurisdictions where data were adequate.** Series coverage in this report includes the following doses of vaccines: ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP); ≥3 doses of inactivated poliovirus vaccine (IPV); ≥1 dose of measles, mumps, and rubella vaccine (MMR); ≥3 doses of Haemophilus influenzae type B (Hib) vaccine; ≥3 doses of hepatitis B (HepB) vaccine; and ≥4 doses of pneumococcal conjugate vaccine (PCV); i.e., 4:3:1:3:3:4. Coverage with ≥3 doses of rotavirus vaccine was also assessed. Completion of the recommended series of each of these vaccines †† was <90% in all jurisdictions except Palau. Coverage with the full recommended six-vaccine series (4:3:1:3:3:4) ranged from 19.5% (Chuuk) to 69.1% (Palau). In RMI and Chuuk, coverage was lower in the outer islands than in the main islands for most vaccines, with differences ranging from 0.9 to 66.8 percentage points. Medical record abstraction enabled rapid vaccination coverage assessment and timely dissemination of results to guide programmatic decision-making. Effectively monitoring vaccination coverage, coupled with implementation of data-driven interventions

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial.

PubMed

Mo, Zhaojun; Mo, Yi; Li, Mingqiang; Tao, Junhui; Yang, Xu; Kong, Jilian; Wei, Dingkai; Fu, Botao; Liao, Xueyan; Chu, Jianli; Qiu, Yuanzheng; Hille, Darcy A; Nelson, Micki; Kaplan, Susan S

2017-10-13

A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE). 4040 participants aged 6-12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385). VE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related. In Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well

Analysis of the association between millennium development goals 4 & 5 and the physician workforce across international economic strata.

PubMed

Morley, Christopher P; Wang, Dongliang; Mader, Emily M; Plante, Kyle P; Kingston, Lindsey N; Rabiei, Azadeh

2017-07-18

The Millennium Development Goals (MDGs) are 8 international development goals voluntarily adopted by 189 nations. The goals included health related aims to reduce the under-five child mortality rate by two-thirds (MDG4), and to reduce the maternal mortality ratio by three-quarters (MDG5). To assess the relationship between the healthcare workforce and MDGs 4-5, we examined the physician workforces of countries around the globe, in terms of the Physician Density Level (PDL, or number of physicians per 1000 population), and compared this rate across a number of years to several indicator variables specified as markers of progress towards MDG4 and MDG5. Data for each variable of interest were obtained from the World Bank's Millennium Development Goals and World Development Indicators databases for 208 countries and territories from 2004 to 2014, representing a ten-year period for which the most information is available. We analyzed the relationships between MDG outcomes and PDL, controlling for national income levels and other covariates, using linear mixed model regression. Dependent variables were logarithmically transformed to meet assumptions necessary for multivariate analysis. In unadjusted models, an increase of every one physician per 1000 population (one unit change in PDL) lowered the risk of not being vaccinated for measles-mumps-rubella (MMR) to 29.3% (p < 0.001, 95% CI: 22.2%-38.7%) and for not receiving diphtheria-tetanus-pertussis (DTaP) vaccination rate decreased to 38.5% (p < 0.001, 95% CI: 28.7% - 51.7%). Maternal mortality rate decreased to 76.6% (p < 0.001, 95% CI: 74.3% - 79.0%), neonatal mortality decreased to 58.8% (p < 0.001, 95% CI: 54.8% - 63.2%) and under-5 mortality rate decreased to 52.1% (p < 0.001, 95% CI: 48.0% - 56.4%), with every one-unit change in PDL. Adjusted models tended to reflect unadjusted risk assessments. The maintenance and improvement of the health workforce is a vital consideration when assessing how to achieve

Vaccine information statements. Revolutionary but neglected educational advances in healthcare in the United States.

PubMed

Edlich, Richard F; Martin, Marcus L; Foley, Marni L; Gebhart, Jocelynn H; Winters, Kathryne L; Britt, L D; Long, William B; Gubler, K Dean

2005-01-01

The purpose of this report is to provide further information about vaccine information statements (VISs) that are revolutionary but neglected educational advances in the United States. Because the use of VISs is mandated by the Federal Government in every individual being immunized, it is the goal of this report to further awaken health professionals and society to the mandatory use of these superb educational statements. With the passage of the National Childhood Vaccine Injury Act of 1986, the Federal Government required that VISs would be given to all vaccine recipients. As of September 2001, the VISs that must be used are diphtheria, tetanus, pertussis, (DTaP); diphtheria, tetanus (Td); measles, mumps, rubella (MMR); polio (IPV); hepatitis B; Haemophilus influenzae type b (Hib); varicella; and pneumococcal conjugate. Copies of the VISs are available at www.cdc.gov/nip/publications/VIS. The National Childhood Vaccine Injury Act of 1986 mandated that all health care providers report certain adverse events that occur following vaccination. As a result, the Vaccine Adverse Events Reporting System (VAERS) was established by the FDA and the Centers for Disease Control and Prevention (CDC) in 1990. In order to reduce the liability of manufacturers and healthcare providers, the National Childhood Vaccine Injury Act of 1986 established the National Vaccine Injury Compensation Program (NVICP). This program is intended to compensate those individuals who have been injured by vaccines on a no-fault basis. While the use of VISs has been mandated since 1996, a national survey of private practice office settings has revealed that many immunized patients do not receive the VISs. When these forms were used, physicians rarely initiated discussions regarding contraindications to immunizations or the National Vaccine Injury Compensation Program. Fortunately, the state boards of medical examiners, like the one in Oregon, are taking a strong stand for the use of VISs, with the

Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP).

PubMed

Broder, Karen R; Cortese, Margaret M; Iskander, John K; Kretsinger, Katrina; Slade, Barbara A; Brown, Kristin H; Mijalski, Christina M; Tiwari, Tejpratap; Weston, Emily J; Cohn, Amanda C; Srivastava, Pamela U; Moran, John S; Schwartz, Benjamin; Murphy, Trudy V

2006-03-24

During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologicals, Rixensart, Belgium [licensed May 3, 2005, for use in persons aged 10-18 years], and ADACEL, sanofi pasteur, Toronto, Ontario, Canada [licensed June 10, 2005, for use in persons aged 11-64 years]). Prelicensure studies demonstrated safety and efficacy against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adolescents. To reduce pertussis morbidity in adolescents and maintain the standard of care for tetanus and diphtheria protection, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adolescents aged 11-18 years should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP)/ diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series (five doses of pediatric DTP/DTaP before the seventh birthday; if the fourth dose was administered on or after the fourth birthday, the fifth dose is not needed) and have not received Td or Tdap. The preferred age for Tdap vaccination is 11-12 years; 2) adolescents aged 11-18 years who received Td, but not Tdap, are encouraged to receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTP/DTaP vaccination series. An interval of at least 5 years between Td and Tdap is encouraged to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval less than 5 years between Td and Tdap can be used; and 3) vaccine providers should administer Tdap and tetravalent meningococcal conjugate

Prevention of pertussis among adolescents: recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.

PubMed

2006-03-01

The purpose of this statement is to provide the rationale and recommendations for adolescent use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Despite universal immunization of children with multiple doses of pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, pertussis remains endemic with a steady increase in the number of reported cases. Two peaks in the incidence of pertussis occur in pediatric patients: infants younger than 6 months of age who are inadequately protected by the current immunization schedule and adolescents 11 through 18 years of age whose vaccine-induced immunity has waned. Significant medical and public health resources are being consumed in postexposure management of adolescent cases, contacts, and outbreaks with little beneficial effect on individuals or the epidemiology of disease. Two Tdap products were licensed in 2005 for use in people 10 through 18 years of age (Boostrix) and 11 through 64 years of age (Adacel). The American Academy of Pediatrics recommends the following: 1. Adolescents 11 to 18 years of age should receive a single dose of Tdap instead of tetanus and diphtheria toxoids (Td) vaccine for booster immunization. The preferred age for Tdap immunization is 11 to 12 years. 2. Adolescents 11 to 18 years of age who have received Td but not Tdap are encouraged to receive a single dose of Tdap. An interval of at least 5 years between Td and Tdap is suggested to reduce the risk of local and systemic reactions; however, intervals of less than 5 years can be used, particularly in settings of increased risk of acquiring pertussis, having complicated disease, or transmitting infection to vulnerable contacts. Data support acceptable safety with an interval as short as approximately 2 years. 3. Tdap and tetravalent meningococcal conjugate vaccine (MCV4 [Menactra]) should be administered during the same visit if both vaccines are indicated. If this is not feasible, MCV4

[Immunisation schedule of the Spanish Association of Paediatrics: 2014 recommendations].

PubMed

Moreno-Pérez, D; Alvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

2014-01-01

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded, as routine vaccinations, those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in special situations. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Based on the latest epidemiological trends, CAV-AEP recommends the administration of the first dose of MMR and varicella vaccines at age 12 months, with the second dose at age 2-3 years; the administration of DTaP or Tdap vaccine at age 4-6 years, always followed by another Tdap dose at 11-12 years; and the three meningococcal C scheme at 2 months, 12 months and 12 years of age. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-12 years must be increased. Universal vaccination against varicella in the second year of life is an effective strategy, and the immediate public availability of the vaccine is requested in order to guarantee the right of healthy children to be vaccinated. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. The recently authorised meningococcal B vaccine has opened a chapter of hope in the

Safety and immunogenicity of a diphtheria, tetanus, acellular pertussis and Haemophilus influenzae Type b combination vaccine compared with separate administration of licensed equivalent vaccines in Chinese infants and toddlers for primary and booster immunization.

PubMed

Li, Guifan; Zhang, Huajie; Zhou, Weizhong; Ye, Qiang; Li, Fengxiang; Wang, Hua; Hou, Qiming; Xu, Yinghua; Ma, Xiao; Tan, Yajun; Wang, Lichan; Li, Yanan; Li, Hong; Meng, Fanyue; Liang, Qi; Liu, Aimin; Qin, Chengkui; Wei, Wenjin; Liu, Jiankai; Ruan, Chengmai; Tao, Wenjian; Zhang, Shumin; Zheng, Haifa; Zhu, Fengcai

2010-06-07

To evaluate the safety and immunogenicity of a diphtheria, tetanus, acellular pertussis and Haemophilus infuenzae Type b (DTaP/Hib) combination vaccine first developed by a Chinese manufacturer, a randomized, two-stage, parallel controlled, single center clinical trial was conducted in Dafeng, Jiangsu Province of China. A total of 720 infants were enrolled and randomly assigned to two groups with a 2:1 allocation. In Stage I, 480 subjects in Group T were administered with 3 doses of the DTaP/Hib vaccine at 3, 4 and 5 months of age, respectively, while 240 subjects in Group C received separate licensed DTaP vaccine and Hib conjugate vaccine on the same schedule. In Stage II, 633 primed toddlers (431 of Group T and 202 of Group C) were given a booster dose at 18 months of age. Sera samples were collected at pre-dose 1, 4 weeks post-dose 3, pre-dose 4 and 4 weeks post-dose 4, respectively. Levels of protective antibodies were measured by Enzyme Linked Immunoadsorbent Assay (ELISA). Immunogenicity was evaluated with regard to geometric mean concentrations (GMCs), seroconversion rates and seroprotection rates of the antibodies. Solicited adverse reactions were recorded for 3 days after each dose; unsolicited adverse events and serious adverse events were monitored for 28 days after vaccination. Results showed that seroconversion rates of anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA), anti-diphtheria toxoid (DT), anti-tetanus toxid (TT) and anti-polyribosyl-ribitol-phosphate (PRP) in Group T (Stage I: 98.06%, 97.33%, 100%, 100%, 98.79%; Stage II: 99.18%, 83.42%, 99.18%, 63.32%, 85.05%) were comparable to that of Group C (Stage I: 95.26%, 93.16%, 100%, 100%, 98.42%; Stage II: 98.89%, 83.89%, 98.33%, 53.89%, 76.67%). Nearly 100% of the subjects in both groups achieved seroprotective levels of anti-DT (> or = 0.1IU/ml), anti-TT (> or = 0.1IU/ml) and anti-PRP (> or = 0.15 microg/ml) after primary and booster vaccination. The frequencies of local induration