作者: Ma, Jennie Z ; Carmolli, Marya ; van der Klis, Fiona ; Kirkpatrick, Beth ; Haque, Rashidul ; Mondal, Dinesh ; Naylor, Caitlin ; Buonomo, Erica ; Colgate, Ross ; Mychaleckyj, Josyf C ; Dickson, Dorothy ; Lu, Miao ; Nayak, Uma ; Weldon, William ; Petri, William A ; Steven Oberste, M

BACKGROUNDEnvironmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh.METHODSWe conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647.FINDINGSEE was present in greater than 80% of infants by 12 weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ < - 2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers.INTERPRETATIONEE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine underperformance and risk for future growth faltering. These results offer a potential explanation for the burden of these problems in low-income problems, allow early identification of infants at risk, and suggest pathways for intervention.FUNDINGThe Bill and Melinda Gates Foundation (OPP1017093).

2013-09-01·Human Immunology4区 · 医学

CD4+ CD31+ recent thymic emigrants in CHD7 haploinsufficiency (CHARGE syndrome): A case

4区 · 医学

Article

作者: Hans O. Madsen ; Niels Fisker ; Christian Nielsen ; Lars P. Ryder ; Maria Kirchhoff ; Kristian Assing

Lymphocyte counts <2000 cells/μL are associated with early death in infants with CHARGE (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) syndrome and CHD7 haploinsufficiency. Absence of recent thymic emigrants is also accompanied by an Omenn-like syndrome and infant death in CHD7 haploinsufficiency. Studies positively identifying recent thymic emigrants, in relation to CHD7 haploinsufficiency, are non-existent. Thirty two months of flow-cytometric work-up of an athymic (evaluated by four chest X-rays) infant, with a novel CHD7 deletion, demonstrated sparse (<50 cells/mm(3)) but continuous egress of recent thymic emigrants (CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+)) and homeostatic lymphocyte expansion. Infectious or autoimmune episodes (e.g., Omenn-like syndrome) were not detected (despite lymphocyte counts <2000 cells/μL) and excellent vaccination (tetanus, Haemophilus influenzae type B and pneumococcal conjugate vaccines) and proliferation (anti-CD3 and anti-CD28 stimulated) responses were recorded. Her CD4(+) T cells displayed Gaussian distributed TCR (CDR3) spectratypes (22 functional Vβ families). Her CD4(+) T cell profile was also characterized by a slightly increased proportion CD4(+) CD25(+) FoxP3(+) T cells. Since CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+) RTE are reported to be TCR diverse and to contain regulatory T cells, we found it important to report that continuously reduced numbers of CD3(+) CD4(+) CD45RA(+) CD45RO(-) CD31(+) RTE, in the context of CHD7 haploinsufficiency and despite severe lymphopenia, is consistent with an uneventful clinical outcome.

2012-02-08·JAMA1区 · 医学

Immunogenicity and Tolerability of Recombinant Serogroup B Meningococcal Vaccine Administered With or Without Routine Infant Vaccinations According to Different Immunization Schedules

1区 · 医学

Article

作者: Gianni Bona ; Ly-Mee Yu ; Peter Dull ; Adam Finn ; Roman Prymula ; Javier Diez-Domingo ; Dorothee Kieninger ; Nicola Principi ; Andrew J. Pollard ; Birgitta Becker ; Nicoletta Gossger ; Alan Kimura ; Matthew D. Snape ; Ellen Ypma ; Daniela Toneatto ; Susanna Esposito ; Etienne Sokal

CONTEXTIn the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries.OBJECTIVETo determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately.DESIGN, SETTING, AND PARTICIPANTSPhase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe.INTERVENTIONParticipants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months.MAIN OUTCOME MEASURESPercentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99).RESULTSAfter three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together.CONCLUSIONA 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations.TRIAL REGISTRATIONclinicaltrials.gov Identifier: NCT00721396.

100 项与白喉，破伤风，百日咳，乙肝，b型流感嗜血杆菌吸附结合疫苗(Serum Institute of India Pvt Ltd.) 相关的药物交易

登录后查看更多信息

研发状态

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
白喉	印度	Serum Institute of India Pvt Ltd.	-
嗜血杆菌感染	印度	Serum Institute of India Pvt Ltd.	-
乙型肝炎	印度	Serum Institute of India Pvt Ltd.	-
破伤风	印度	Serum Institute of India Pvt Ltd.	-
百日咳	印度	Serum Institute of India Pvt Ltd.	-