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1.
Myroslawa Happe Devadoss J. Samuvel Jennifer A. Ohtola Jeff E. Korte M.A. Julie Westerink 《Vaccine》2019,37(12):1622-1629
Background
Both HIV positivity and African American (AA) ethnicity are associated with increased incidence of invasive pneumococcal disease (IPD). Poor immune response to pneumococcal polysaccharide-based vaccines may contribute to the race related increased frequency of IPD in African American HIV positive individuals.Methods
Caucasian and AA HIV-infected (HIV+) individuals 40–65?years old with CD4+ T cells/µl (CD4) >200 on antiretroviral therapy (ART) received either the 13-valent pneumococcal conjugate vaccine (PCV) followed by the 23-valent pneumococcal polysaccharide vaccine (PPV) or PPV only. Serum IgG, IgM and opsonophagocytic antibody responses to serotypes 14 and 23F as well as serum IgG and opsonophagocytic antibody responses to serotype 19A were measured pre- and post-vaccination. We measured serum markers of inflammation in all participants and performed single cell gene expression profiling at the baseline by HD Biomark in Caucasians and African Americans.Results
There were no significant differences in pre-immunization inflammatory markers or post-vaccination IgG and IgM concentrations between Caucasian and African American participants. However, we found significantly lower opsonophagocytic activity in response to serotypes 14 and 19A in the AA group compared to the Caucasian group. There was no association between inflammatory markers and immune response to vaccination, however we found extensive biomodal variation in gene expression levels in single IgM+ memory B cells. Differentially expressed genes may be related to differences in the immune response between ethnic groups.Conclusions
Distinct racial differences were found in the functional immune response following either PPV and/or PCV/PPV immunization in HIV-positive adults, although these differences were serotype dependent. Decreased ability to respond to vaccination may in part explain racial disparities in pneumococcal disease epidemiology.ClinicalTrials.gov ID: NCT03039491. 相似文献2.
Aderonke Odutola Martin O.C. Ota Martin Antonio Ezra O. Ogundare Yauba Saidu Patrick K. Owiafe Archibald Worwui Olubukola T. Idoko Olumuyiwa Owolabi Beate Kampmann Brian M. Greenwood Mark Alderson Magali Traskine Kristien Swinnen Vincent Verlant Kurt Dobbelaere Dorota Borys 《Vaccine》2019,37(19):2586-2599
Background
Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines.Methods
In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 8–10?weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4?months [M]) of PHiD-CV/dPly/PhtD (10 or 30?µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9?M) of PHiD-CV/dPly/PhtD (30?µg of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4?M, and measles, yellow fever, and OPV vaccines at 9?M. We evaluated immune responses at 2-5-9-12?M; and reactogenicity 0–3?days post-vaccination.Results
1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1?M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, ≥97.4% (3+0 schedule) and ≥96.4% (2+1 schedule) of infants had antibody concentrations ≥0.2?μg/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1?M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns.Conclusion
Immune responses to the 10 PHiD-CV polysaccharide conjugates and co-administered vaccines were not altered by addition of dPly and PhtD. ClinicalTrials.gov identifier NCT01262872. 相似文献3.
Lisa A. Jackson Alejandra Gurtman Martin van Cleeff Kathrin U. Jansen Deepthi Jayawardene Carmel Devlin Daniel A. Scott Emilio A. Emini William C. Gruber Beate Schmoele-Thoma 《Vaccine》2013
Background
Streptococcus pneumoniae is a major cause of morbidity and mortality among adults 50 years of age and older in the United States. Pneumococcal conjugate vaccines are efficacious against pneumococcal disease in children and may also offer advantages in adults.Methods
We performed a randomized, modified double-blind trial that compared a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in 831 pneumococcal vaccine naive adults 60–64 years of age. An additional group of 403 adults 50–59 years of age received open-label PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured at baseline, and at 1 month and 1 year after vaccination.Results
In the randomized trial, the month 1 post-vaccination OPA geometric mean titers in the PCV13 group were statistically significantly higher than in the PPSV23 group for 8 of the 12 serotypes common to both vaccines and for serotype 6A, a serotype unique to PCV13, and were comparable for the other 4 common serotypes. The immune response to PCV13 was generally greater in adults 50–59 years of age compared to adults 60–64 years of age. OPA titers declined from 1 month to 1 year after PCV13 administration but remained higher than pre-vaccination baseline titers.Conclusions
PCV13 induces a greater functional immune response than PPSV23 for the majority of serotypes covered by PCV13, suggesting that PCV13 could offer immunological advantages over PPSV23 for prevention of vaccine-type pneumococcal infection. 相似文献4.
Shalom Ben-Shimol Noga Givon-Lavi Eugene Leibovitz David Greenberg Ron Dagan 《Vaccine》2019,37(1):1-6
Background
Complex otitis media (OM) may present with intact tympanic membrane or spontaneous otorrhea. We compared dynamics of intact tympanic membrane and spontaneous otorrhea OM following 7- and 13-valent conjugated vaccines (PCV7, PCV13) implementation, since differences in dynamics may imply different underlying mechanisms.Methods
A prospective, population-based, active surveillance. Episodes with middle-ear fluid cultures in children?<?3?years were included. Defined sub-periods were: pre-pneumococcal conjugated vaccines (PCV) (2004–2008); PCV7 (2009–2011); PCV13 (2014–2016).Results
Of 7705 episodes, 57.2% had intact tympanic membrane, 16.8% spontaneous otorrhea, 26.0% unknown.In the pre-PCV period, the spontaneous otorrhea group was older and had higher proportions of factors associated with recurrence/chronicity.During the PCV7 period, spontaneous otorrhea and intact tympanic membrane episodes caused by PCV13 serotypes decreased significantly (43% and 51%, respectively) and those caused by non-PCV13 serotypes and culture-negative episodes increased significantly. However, rates increases were steeper in the spontaneous otorrhea group for both non-PCV13 serotypes (117% vs. 38%) and culture-negative (720% vs. 69%). In the spontaneous otorrhea group, nontypeable Haemophilus influenzae rates increased non-significantly by 10% and all-cause OM rates increased significantly by 56%, while in the intact tympanic membrane group the respective rates decreased significantly by 22% and 11%. These trends were especially pronounced in ages 24–35?months.Despite these differences, after PCV13 introduction, both spontaneous otorrhea and intact tympanic membrane rates declined for all outcomes.Conclusions
Spontaneous otorrhea was associated with older age, frequent history of complex OM and delayed PCV impact, suggesting a higher proportion of advanced-stage complex OM. 相似文献5.
Alexandre C. Fortanier Roderick P. Venekamp Arno W. Hoes Anne G.M. Schilder 《Vaccine》2019,37(11):1528-1532
Background
It has been hypothesized that widespread implementation of pneumococcal conjugate vaccination (PCV) in infancy reduces early AOM and thereby prevents further AOM episodes and associated health care resource use.Methods
We tested this hypothesis by applying an extension of the original Cox proportional hazards model (Prentice, Williams and Petersons’ total time) to individual AOM episodes recorded in pseudonymised primary care electronic health records of 18,237 Dutch children born between 2004 and 2015. Children were assigned to three groups: no-PCV (January 2004-March 2006), PCV7 (April 2006-February 2011) and PCV10 (March 2011-February 2015).Results
Of the 18,237 newborns, 6967 (38%) experienced at least one GP-diagnosed AOM episode up to the age of four years (median age at first AOM: 12?months, interquartile range: 12; total number of AOM episodes: 14,689). Time-to-first AOM was longest in the PCV10 group compared with the PCV7 and no-PCV groups (log rank test: P?<?0.001); in these groups 30% had experienced a first AOM at 20, 17 and 15?months, respectively. Children in the PCV10 group had a 21% lower risk of experiencing a first AOM episode than those in the no-PCV group (hazard ratio (HR): 0.79, 95% confidence interval (CI): 0.72–0.86), while the effect was less pronounced for the PCV7 group (HR: 0.94, 95% CI: 0.87–1.02). Neither PCV7 nor PCV10 reduced the risk of AOM recurrences. Compared to no-PCV, HRs for overall AOM were 1.00 (95% CI: 0.95–1.06) and 0.89 (95% CI: 0.84–0.95) for PCV7 and PCV10, respectively.Conclusion
Our cohort study suggests that PCV postpones the onset and reduces the risk of first AOM without affecting recurrences. The impact of PCV on overall AOM in children up to the age of four years seems therefore largely attributable to the prevention of a first AOM episode. 相似文献6.
Jennifer Milucky Maria de Gloria Carvalho Nadine Rouphael Nancy M. Bennett H.Keipp Talbot Lee H. Harrison Monica M. Farley Jeremy Walston Fabiana Pimenta Fernanda C. Lessa 《Vaccine》2019,37(8):1094-1100
Background
Vaccination of children with 13-valent pneumococcal conjugate vaccine (PCV13) led to declines in vaccine-type pneumococcal nasopharyngeal carriage among adults through indirect effects. In August 2014, PCV13 immunization of all U.S. adults ≥65?years of age was recommended. This study sought to define prevalence and serotype distribution of pneumococcal carriage among adults ≥65?years of age and to describe risk factors for colonization soon after introduction of PCV13 in adults.Methods
A cross-sectional survey of non-institutionalized U.S. adults ≥65?years of age was conducted in four states in 2015–2016. Demographic information, risk factors for disease, PCV13 vaccination history, and nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected. NP and OP swabs were processed separately and pneumococcal isolates were serotyped by Quellung reaction. Antimicrobial susceptibility of pneumococcal isolates was performed. NP swabs also underwent real-time PCR for pneumococcal detection and serotyping.Results
Of 2989 participants, 45.3% (1354/2989) had been vaccinated with PCV13. Fifty-five (1.8%) carried pneumococcus (45 identified by culture and 10 by real-time PCR only) and PCV13 serotypes were found in eight (0.3%) participants. Almost half (22/45) of pneumococcal isolates were not susceptible to at least one of the antibiotics tested. Vaccine-type carriage among vaccinated and unvaccinated individuals was similar (0.2% vs. 0.1%, respectively). Respiratory symptoms were associated with higher odds of pneumococcal colonization (adjusted OR: 2.1; 95% CI?=?1.1–3.8).Conclusions
Pneumococcal carriage among non-institutionalized adults ≥65?years of age was very low. Less than 0.5% of both vaccinated and unvaccinated individuals in our study carried vaccine-type serotypes. Over a decade of PCV vaccination of children likely led to indirect effects in adults. However, given the low vaccine-type carriage rates we observed in an already high PCV13 adult coverage setting, it is difficult to attribute our findings to the direct versus indirect effects of PCV13 on adult carriage. 相似文献7.
Background
In June, 2012 a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was added to the recommendation for immunocompromised adults who were previously recommended to receive only 23-valent pneumococcal polysaccharide vaccine (PPSV23). PCV13 may be more effective, though it covers fewer disease-causing strains.Objective
We examined the incremental cost-effectiveness of adding one dose of PCV13 to the pre-2012 recommendation of PPSV23 for adults with 4 immunocompromising conditions who are at increased risk of pneumococcal disease: HIV/AIDS, hematologic cancer, solid organ transplants, and end stage renal disease.Methods
We used a probabilistic model following a single cohort of 302,397 immunocompromised adults. We used vaccination coverage and disease incidence data specific to each immunocompromising condition. Assumptions about PPSV23 and PCV13 vaccine effectiveness were based on two randomized controlled trials and several observational studies conducted among HIV-infected adults. Because no such studies have been conducted among other immunocompromised populations, we made further assumptions about the relative vaccine effectiveness in those groups. Cost-effectiveness ratios were determined for each condition and for all 4 groups in total.Results
Our model indicated that adding one dose of PCV13 to adults in the United States with 4 immunocompromising conditions would cost $16 million (in 2009$) but provide off-setting savings of $21 million per cohort from the societal perspective. These savings come largely from decreased medical costs among adults with end stage renal disease. This dose of PCV13 would prevent 57 cases of invasive pneumococcal disease, 619 cases of hospitalized all-cause pneumonia, avert 93 deaths, and save 1360 quality adjusted life years per cohort.Conclusion
The addition of one dose of PCV13 to the previously recommended PPSV23 doses for adults with selected immunocompromised conditions potentially reduces both disease and costs. 相似文献8.
Richard N. Greenberg Alejandra Gurtman Robert W. Frenck Cynthia Strout Kathrin U. Jansen James Trammel Daniel A. Scott Emilio A. Emini William C. Gruber Beate Schmoele-Thoma 《Vaccine》2014
Background
Unlike free pneumococcal polysaccharide vaccines (PPSVs), pneumococcal conjugate vaccines (PCVs) induce a T–cell–dependent immune response. The study assessed potential influence of initial 13-valent PCV (PCV13) or 23-valent PPSV (PPSV23) on subsequent vaccine administrations.Methods
We conducted a randomized, modified double-blind study in 720 pneumococcal vaccine–naïve adults 60–64 years of age. Subjects received either PCV13 at year 0 and PCV13 at year 1; PCV13 at year 0 and PPSV23 at year 1; or PPSV23 at year 0 and PCV13 at year 1. Antipneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after each vaccination.Results
OPA titers following PPSV23 given 1 year after PCV13 (PCV13/PPSV23) (a) were noninferior for the 12 common serotypes and significantly higher for 6 of 12 common serotypes than those following only an initial PPSV23; and (b) were significantly higher for 11 of 12 common serotypes compared with PPSV23 followed by PCV13 (PPSV23/PCV13). In addition, PPSV23 followed 1 year later by PCV13 (PPSV23/PCV13) elicited significantly lower OPA titers than after only an initial dose of PCV13 for all 13 serotypes. Responses after a second vaccination with either PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for 9 of 13 and 8 of 12 common serotypes compared with the initial PCV13 dose.Conclusion
In pneumococcal vaccine–naïve adults 60–64 years of age, an initial PCV13 augmented the antipneumococcal response to subsequent administration of PPSV23 for many of the serotypes in common to both vaccines. In contrast, an initial PPSV23 resulted in a diminished response to subsequent administration of PCV13 for all serotypes. With a relatively short 1-year interval between doses, responses after a second vaccination with PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for a majority of serotypes compared with the initial PCV13 dose, probably reflecting the need for a longer interval between vaccine administrations.ClinicalTrials.gov Identifier: NCT00574548. 相似文献9.
The introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 dramatically reduced the incidence of invasive pneumococcal disease (IPD) caused by the seven serotypes covered by the vaccine. Following the introduction of PCV7, which contains a serotype 6B conjugate, some decrease in IPD due to serotype 6A was noted suggesting that the serotype 6B conjugate provided some partial cross-protection against serotype 6A. However, no effect on serotype 6C was observed. In 2010, a pneumococcal conjugate vaccine with expanded serotype coverage (PCV13) was introduced that expanded the serotype coverage to 13 serotypes including serotype 6A. To assess whether the 6A conjugate in PCV13 could potentially induce functional anti-6C antibody responses, an opsonophagocytic assay (OPA) for serotype 6C was developed. Randomly chosen subsets of immune sera collected from infants receiving three doses of PCV7 or PCV13 were tested in OPA assays for serotype 6A, 6B and 6C. PCV7 immune sera demonstrated strong OPA responses, defined as percentage of subjects having an OPA titer ≥1:8, to serotype 6B (100% responders), partial responses to serotype 6A (70% responders) but only minimal responses to serotype 6C (22% responders). In contrast, PCV13 immune sera showed strong OPA responses to serotypes 6A (100% responders), 6B (100% responders) and 6C (96% responders). Furthermore, during pre-clinical work it was observed that serotype 7F (included in PCV13) and serotype 7A (not included in PCV13) shared serogroup-specific epitopes. To determine whether such epitopes also may be eliciting cross-functional antibody, PCV13 immune sera were also tested in serotype 7A and 7F OPA assays. All PCV13 immune sera demonstrated OPA responses to both of these serotypes. Taken together these results suggest that immunization with PCV13 has the potential to induce cross-protective responses to related serotypes not directly covered by the vaccine. 相似文献
10.
Alfonso Carmona Martinez Roman Prymula Mariano Miranda Valdivieso Maria del Carmen Otero Reigada Jose Manuel Merino Arribas Jerzy Brzostek Leszek Szenborn Renata Ruzkova Michael R. Horn Teresa Jackowska Fernando Centeno-Malfaz Magali Traskine Kurt Dobbelaere Dorota Borys 《Vaccine》2019,37(1):176-186
Background
We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM197-conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent).Methods
In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM197-conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12–15?months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2?μg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed.Results
951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2?µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded.Conclusion
Addition of 19A and 6A CRM197-conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV.Clinical trial registry: NCT01204658. 相似文献11.
Background
Aboriginal and Torres Strait Islander (Indigenous) Australians have high rates of invasive pneumococcal disease (IPD), with repeat doses of 23-valent polysaccharide pneumococcal vaccine (PPV23) recommended. We report the relative effectiveness of revaccination using a cohort from linked administrative data.Methods
All resident North Queensland Indigenous adults who received any PPV23 vaccination between 2000 and 2012 were identified and linked with IPD cases. IPD rates were compared for individuals revaccinated >five years after initial PPV23 dose against individuals not revaccinated.Results
Analysed data included 12,809 individuals and 89,612 person-years. Revaccinated adults had similar rates of IPD as non-revaccinated adults, after adjusting for potential confounders (HR?=?0.92; 95%CI: 0.35–2.42). Findings were similar for vaccine-specific serotypes (HR?=?1.32; 95%CI: 0.32–5.43).Conclusions
Benefits of PPV23 revaccination against IPD in this high-risk population were not demonstrated, although estimates were imprecise. Findings should be validated in other high-risk cohorts, and against all-cause pneumonia as an outcome. 相似文献12.
Objectives
We evaluated the effect of the infant 7-valent pneumococcal conjugate vaccine (PCV7) program on the serotype distribution in invasive pneumococcal disease in the Belgian population.Methods
Serotyping was performed on 13,998 bacteraemic and pleural fluid isolates sent to the National Reference Laboratory between 2002 and 2010. We compared the distribution of serogroups (SGs) between the pre- (2002–2004) and post-PCV7 (2007–2010) era for children (<18 years), adults (18–59 years) and older individuals (≥60 years).Results
The proportion of cases caused by PCV7-SGs in subjects <18 years decreased from 69% pre-PCV7 to 26% post-PCV7 (p < 0.005) and the majority of cases caused by PCV7-SGs were caused by SG 19. Post-PCV7, the prevalence of PCV7-SGs decreased from 38% to 29% and from 57% to 35% in subjects in the age groups 18–59 and ≥60 years, respectively (p < 0.005). Post-PCV7 the prevalence of SGs 1, 7 and 19 increased significantly in subjects aged <18 years. The increase of SG19 was caused by an increase of serotype 19A in this age group (p < 0.005). After the introduction of infant PCV7 the largest rise in prevalence occurred for SGs 7, 12 and 22 (p < 0.005) in the two older age categories. Post PCV7, the overall PCV13 and 23-valent pneumococcal polysaccharide vaccine coverage rates decreased from 85% to 69% and from 96% to 93%, respectively (p < 0.005).Conclusions
PCV7 has an impact on SG distribution of invasive pneumococcal disease isolates of vaccinated and unvaccinated subjects. SG replacement forms a major threat to the success of PCV7. PCV13, including several additional replacement serotypes (STs 1, 7F, 19A), represents an attractive alternative. 相似文献13.
Gail L. Rodgers Susanna Esposito Nicola Principi Maricruz Gutierrez-Brito Javier Diez-Domingo Andrew J. Pollard Matthew D. Snape Federico Martinón-Torres William C. Gruber Scott Patterson Allison Thompson Alejandra Gurtman Peter Paradiso Daniel A. Scott 《Vaccine》2013
Background
The 7-valent pneumococcal conjugate vaccine (PCV7) has demonstrated effectiveness against pneumococcal illnesses when administered as 3 infant doses plus a toddler dose (3+1 schedule) or as an abbreviated schedule of 2 infant doses plus a toddler dose (2+1 schedule). The 13-valent pneumococcal conjugate vaccine (PCV13) is approved and World Health Organization-prequalified for administration in a 2+1 schedule when used as part of routine immunization programs.Objective
To summarize immunologic responses elicited by PCV13 administered in a 2+1 schedule and following 2 doses in a 3+1 schedule.Methods
Studies were double-blind, randomized, active-controlled, multicenter studies except the Mexico study (open-label, single-arm). In 2+1 studies, PCV13 was administered at 2, 4, and 12 (UK) or 3, 5, and 11 (Italy) months. In 3+1 studies (Spain and Mexico), assessment was made postdose 2 of the primary series (2, 4, and 6 months). The primary immunogenicity endpoint was the proportion of participants achieving serotype-specific antipolysaccharide immunoglobulin (Ig)G concentrations ≥0.35 μg/mL (i.e., responders) 1 month postdose 2. Pneumococcal IgG geometric mean concentrations (GMCs), opsonophagocytic activity (OPA), and concomitant vaccine responses were assessed.Results
PCV13 and PCV7 elicited comparable immune responses for the 7 common serotypes after 2 infant doses. The proportion of PCV13 responders postdose 2 was >85% for most of the 7 common and 6 additional serotypes, except common serotypes 6B (27.9–81.4%) and 23F (55.8–77.5%) and additional serotypes 3 (73.8–96.9%) and 6A (79.2–94.4%). Serotypes 6B and 23F elicited lower IgG GMCs postdose 2 compared with other serotypes; all serotypes demonstrated boosting posttoddler dose. All serotypes demonstrated functional activity; >95% of participants achieved OPA levels ≥1:8 postdose 2. Concomitant vaccine responses were similar between PCV13 and PCV7 groups.Conclusion
Immune responses elicited by PCV13 following 2 infant doses support transition from PCV7 to PCV13 in countries using a 2+1 schedule.Clinical trial registration numbers: UK (Study 007) NCT00384059; Italy (Study 500) NCT00366899; Spain (Study 501) NCT00368966; Spain (Study 3007) NCT00474539; and Mexico (Study 3009) NCT00708682. 相似文献14.
Beatriz P. Quiambao Cristina Ambas Sherylle Diego Valérie Bosch Castells Joanna Korejwo Céline Petit Guy Houillon 《Vaccine》2019,37(16):2268-2277
Background
Rabies post-exposure prophylaxis (PEP) via intradermal (ID) administration is standard practice in Asia. Accumulating evidence suggests that PEP shortened to 3 visits in one week does not adversely affect seroconversion rates or immune memory.Objective
To determine whether the seroconversion rate at Day14 with a 1-week, 4-site (4-4-4-0-0) ID vaccination regimen with or without rabies immunoglobulin (RIG) was non-inferior to the updated Thai Red Cross (TRC) 28-day, 2-site (2-2-2-0-2) ID regimen with RIG during rabies PEP. We also assessed one-year antibody persistence.Methods
This phase III, mono-center, open-label, randomized-controlled trial assigned participants aged ≤50?years (n?=?600) exposed to suspected rabid animals and sustaining WHO Category II injuries (automatic allocation to G1) or Category III injuries (randomized to G2 or G3) to the following groups (1:1:1 ratio): G1 (n?=?200), 1-week 4-site ID regimen with the purified Vero cell rabies vaccine (PVRV; Verorab®) without RIG; G2 (n?=?201), 1-week 4-site ID regimen with PVRV, and purified equine rabies immunoglobulin (pERIG); G3 (n?=?199), TRC 28-day, 2-site ID regimen with PVRV, and pERIG. Non-inferiority tests compared G1 vs. G3 and G2 vs. G3. Seroconversion rate was the proportion (%) of vaccinees with rabies virus neutralizing antibodies (RVNA) titers ≥0.5?IU/mL measured by rapid fluorescent focus inhibition test.Results
On Day14, after the third vaccine administration, seroconversion rates were non-inferior in both comparisons and were, respectively, 100%, 99.4%, 98.8% in G1, G2, G3 with a decrease to 97.6%, 89%, 79.8% at Year 1. At Day14, RVNA geometric mean titers were 11.3?IU/mL; 9.89?IU/mL; 6.15?IU/mL, respectively, decreasing to 2.96?IU/mL, 1.37?IU/mL, 0.97?IU/mL at Year1. Safety and tolerability were similar between the three groups.Conclusion
The seroconversion rate at Day 14 with the 1-week 4-site ID regimen, both with and without pERIG, was non-inferior to the reference TRC 28-day 2-site ID regimen with pERIG during rabies PEP with PVRV.ClinicalTrials.gov ID: NCT01622062. 相似文献15.
Lisa A. Jackson Alejandra Gurtman Martin van Cleeff Robert W. Frenck John Treanor Kathrin U. Jansen Daniel A. Scott Emilio A. Emini William C. Gruber Beate Schmoele-Thoma 《Vaccine》2013
Background
Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations.Methods
This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50–64 years in which adults 60–64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50–59 were given PCV13. In this follow up study conducted about 4 years later, the 60–64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50–59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination.Results
A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes.Conclusion
In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses. 相似文献16.
Ioanna N. Grivea Kostas N. Priftis Apostolos Giotas Doxa Kotzia Alexandra G. Tsantouli Konstantinos Douros Aspasia N. Michoula George A. Syrogiannopoulos 《Vaccine》2014
Background
In Greece recently, higher-valent pneumococcal conjugate vaccines (PCVs) replaced the 7-valent (PCV7); the 10-valent (PCV10) became available in May 2009 and the 13-valent (PCV13) in June 2010.Methods
We investigated the nasopharyngeal colonization with Streptococcus pneumoniae in day-care center attendees in Athens and the prefecture of Viotia. Between December 2010 and June 2011, nasopharyngeal cultures were obtained 4 times, at enrollment and then every 6 to 8 weeks.Results
Among the 233 children, 225 (96.6%) had been vaccinated with ≥1 dose of PCV7. One tenth of the PCV7 vaccinated attendees had also received ≥1 dose of PCV13 or PCV10. During the 4 samplings, 358 isolates were recovered from a total of 874 samples. Of the 233 children, 183 (78.5%) were found to carry S. pneumoniae at least once. The overall serotype distribution among carriers was similar regardless of the time lapsed since the last PCV7 dose. A high frequency of 19A (17.1%) coincided with a low frequency of 19F (1.4%). Non-PCV13 serotypes accounted for 73.1% of the isolates; 23B, 15B/C, 16F, 21, 11A, 15A, 6C, 10A, 22F and 23A were the most common. Among attendees aged 24–59 months (median age 42 months), prolonged carriage of a non-PCV13 serotype was relatively common, mainly for 21 and 16F. One out of 4 cases of colonization with the prevalent non-PCV13 serotypes was followed by persistent carriage for 5 to 14 weeks.Conclusions
During this period of transition to the higher-valent PCVs in the day-care center setting, non-PCV13 serotypes dominated and exhibited prolonged colonization. The frequency and the duration of prolonged carriage tends to be increased, if sampling frequency increases and the carriage time before and after positive cultures is taken into consideration. Further studies regarding the fitness of the colonizing non-PCV13 serotypes will likely to be seen in the future. 相似文献17.
Lisa A. Jackson Alejandra Gurtman Kathryn Rice Karlis Pauksens Richard N. Greenberg Thomas R. Jones Daniel A. Scott Emilio A. Emini William C. Gruber Beate Schmoele-Thoma 《Vaccine》2013
Background
The currently recommended single dose of the 23-valent pneumococcal free polysaccharide vaccine (PPSV23) for adults 65 years of age and older does not provide extended protection into older age. This reflects a significant unmet medical need for alternative strategies to protect older adults against pneumococcal infection, which may be met by the 13-valent polysaccharide conjugate vaccine (PCV13).Methods
We performed a randomized, modified double-blind trial in 936 adults aged 70 years and older who had previously received PPSV23 at least 5 years before study entry and were now vaccinated with PCV13 or PPSV23. At 1 year after enrollment, all subjects received a follow-on dose of PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and at 1 month after each vaccination.Results
Following the enrollment vaccination, OPA titers were significantly greater in the PCV13 group compared to the PPSV23 group for 10 of the 12 serotypes common to both vaccines and to serotype 6A which is unique to PCV13. Responses were noninferior for the other 2 common serotypes. Responses to PCV13 given at 1 year were generally lower in the group that received PPSV23 at enrollment.Conclusion
In adults aged 70 years and older previously vaccinated with PPSV23, PCV13 was significantly more immunogenic than PPSV23 for most of the common serotypes and for serotype 6A. The OPA responses after a follow-on dose of PCV13 one year later indicate that a prior dose of PPSV23, but not PCV13, diminishes the response to the subsequent administration of PCV13. 相似文献18.
Fatma Doener Henoch S. Hong Ingo Meyer Keyvan Tadjalli-Mehr Angelika Daehling Regina Heidenreich Sven D. Koch Mariola Fotin-Mleczek Ulrike Gnad-Vogt 《Vaccine》2019,37(13):1819-1826
Background
We report the first-in-concept human trial of the safety, tolerability and immunogenicity when a novel TLR 7/8/RIG I agonist RNA-based adjuvant, CV8102, was administered alone or mixed with fractional doses of a licensed rabies vaccine (Rabipur®) as model antigen.Methods
The primary objective was to assess the safety and reactogenicity of various dose levels of CV8102 alone or mixed with Rabipur® in healthy 18–40 year-old male volunteers. A secondary objective was to assess the immune-enhancing potential of bedside-mixes of CV8102 with fractional doses of Rabipur® by measuring induction of rabies virus neutralising titres (VNTs).Results
Fifty-six volunteers received 50–100?μg CV8102 alone (n?=?11), bedside-mixed CV8102 and Rabipur® (n?=?20), or Rabipur® alone (n?=?25; control). When given alone or mixed with Rabipur® CV8102 caused mostly Grade 1 or 2 local or systemic reactogenicity, but no related SAEs. As 100?µg CV8102 was associated with marked CRP increases further dose escalation was stopped. Combining 25–50?µg of CV8102 with fractional doses of Rabipur® significantly improved the kinetics of VNT responses; 50?µg CV8102 also improved the magnitude of VNT responses to 1/10 Rabipur® but caused severe but self-limiting influenza-like symptoms in 2 of 14 subjects.Conclusions
Doses of 25 and 50?µg CV8102 appeared safe and with an acceptable reactogenicity profile while significantly enhancing the immunogenicity of fractional doses of rabies vaccine.EudraCT No. 2013-004514-18. 相似文献19.
Sung-Ching Pan Szu-Min Hsieh Chih-Feng Lin Yu-Shen Hsu Mingi Chang Shan-Chwen Chang 《Vaccine》2019,37(14):1994-2003
Background
A nasal influenza vaccine has been available only in a live attenuated form, which limits the range of recipients to immune-competent individuals. The present study evaluated a newly developed intranasal inactivated influenza vaccine with a novel adjuvant, heat-labile enterotoxin (LT) derived from E. coli (LTh(αK)).Methods
The study was a randomized, double-blind, controlled phase I trial to evaluate the safety and immunogenicity of an intranasal vaccine containing the trivalent influenza HA antigen (7.5?µg each of A/California/7/09 (H1N1)-like virus, A/Victoria/210/2009 (H3N2) virus, and B/Brisbane/60/2008-like virus) in combination with 4 different doses of adjuvant LTh(αK) (7.5, 15, 30 or 45?μg) and 22.5?μg of influenza HA antigen alone (control vaccine). The vaccine was intranasally administered on Days 0 and 7. A safety evaluation commenced for 180?days, and hemagglutination inhibition (HI) antibody titers and nasal HA-specific IgA titers on Day 0 and Day 28 were assessed to determine whether an immunogenic response was elicited.Results
From November 2012 to September 2013, a total of 36 subjects were enrolled. Twenty-four subjects received an adjuvanted vaccine, and 12 subjects received a control vaccine. The most common adverse event (AE) was mild nasal discomfort, and systemic AEs were mild fatigue and headache. Only two subjects discontinued the study because of an AE (one had grade 3 fever, and one had nodal arrhythmia). In the group with 45?μg of LTh(αK), the seroprotection rates were 100%, 100% and 80%, and the nasal IgA conversion factors were 7.90, 7.46 and 12.27 for the A/H3N2, A/H1N1 and split B strains, respectively. Adjuvant LTh(αK) vaccine showed a significant enhancement in mucosal immunity in split B -specific IgA.Conclusion
The intranasal inactivated influenza vaccine is generally safe, and the LTh(αK)-adjuvanted vaccine is more immunogenic than non-adjuvanted control vaccine.ClinicalTrials.gov Identifier: NCT03293732. 相似文献20.
Javier Diez-Domingo Alejandra Gurtman Enrique Bernaola Francisco Gimenez-Sanchez Federico Martinon-Torres Valentin Pineda-Solas Alfonso Delgado Pilar Infante-Marquez John Z. Liang Peter C. Giardina William C. Gruber Emilio A. Emini Daniel A. Scott 《Vaccine》2013