Safety, Immunogenicity and Dose Ranging of a New Vi-CRM197 Conjugate Vaccine against Typhoid Fever: Randomized Clinical Testing in Healthy Adults

Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine.All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.ClinicalTrials.gov NCT01123941 NCT01193907

Oxidative stress in donor mares for ovum pick-up delays embryonic development

The in vitro production of equine embryos via ovum pick-up (OPU) and intracytoplasmic sperm injection (ICSI) has increased rapidly. There is a marked effect of the individual mare on the outcome of OPU-ICSI, but little is known about the influence of the mare's health condition. This study aimed to investigate the potential associations between the concentrations of interleukin-6 (IL-6), reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) in serum of oocytes' donor mares and the subsequent embryonic development. Just before OPU, a blood sample was collected from 28 Warmblood donor mares, that were subjected to a routine OPU-ICSI program. The serum concentrations of IL-6, d-ROMs, and BAP were assayed photometrically. The maturation, cleavage and blastocyst rate as well as the kinetics of blastocyst development were recorded. The average blastocyst rate was 24.68 ± 5.16% and the average concentrations of IL-6, d-ROMs, and BAP were 519.59 ± 157.08 pg/mL, 171.30 ± 4.55 carratelli units (UCARR), and 2711.30 ± 4.55 μmol/L, respectively. Serum concentrations of IL-6, d-ROMs, and BAP were not significantly different between mares yielding at least one blastocyst (552.68 ± 235.18 pg/mL, 168.36 ± 5.56 UCARR, and 2524.80 ± 159.55 μmol/L) and mares yielding no blastocysts (468.47 ± 179.99 pg/mL, 175.85 ± 7.89 UCARR, and 2999.50 ± 300.13 μmol/L, respectively). Serum concentrations of d-ROMs were significantly lower in mares with fast growing (at day 7–8 post ICSI; 148.10 ± 8.13 UCARR) compared to those with slow growing blastocysts (≥ day 9 post ICSI; 179.41 ± 4.89 UCARR; P = 0.003). Taken together, the serum concentration of IL-6, d-ROMs, and BAP do not determine the mare's ability to produce blastocysts in vitro. Although it may be questioned whether a single sample is representative of the mare's health status, changes in serum metabolites related to oxidative stress at the time of oocyte retrieval were linked to a delayed blastocyst development in a clinical OPU-ICSI outcome

A decade of norovirus disease risk among older adults in upper-middle and high income countries : a systematic review

BACKGROUND: Noroviruses (NoVs) are the most common cause of acute gastroenteritis (AGE) causing both sporadic and outbreak-associated illness. Norovirus (NoV) infections occur across all ages but certain sub-groups are considered at increased risk due to heightened transmission and/or symptom severity. Older adults are potentially at high risk of NoV-associated illness due to frequent outbreaks in long-term care facilities (LTCFs) and severe health outcomes following infection. Elucidation of NoV risk among older adults will support prevention, treatment and control efforts. METHODS: We conducted a systematic literature review to summarize the published risk estimates of NoV-associated illness, hospitalization and death among individuals aged 65 years and older. A structured search using defined NoV and gastroenteritis (GE) terms was performed in the PubMed and EMBASE databases of human studies published between January 1, 2003 and May 16, 2013. RESULTS: We identified 39 studies from high income (HI) and upper-middle income (UMI) countries. Thirty-six percent of publications provided risk estimates based on laboratory-confirmed or epidemiologically-linked population-based surveillance data using molecular diagnostic methods. Over the study period, estimated annual NoV rates and extrapolated number of cases among older adults in HI and UMI countries were: 29-120/10,000 or 1.2–4.8 million NoV-associated illnesses; 18–54/10,000 or 723,000–2.2 million NoV-associated outpatient visits; 1–19/10,000 or 40,00–763,000 NoV-associated inpatient visits; 0.04–0.32/10,000 or 2000–13,000 NoV-associated deaths. NoV was responsible for approximately 10–20 % of GE hospitalizations and 10–15 % of all-cause GE deaths among older adults. Older adults experienced a heightened risk of nosocomial infections. Those in LTCFs experience frequent NoV outbreaks and the range in attack rates was 3–45 %, case hospitalization rates 0.5–6 % and case fatality rates 0.3–1.6 %. CONCLUSIONS: Older adults are at increased risk of severe NoV-associated health outcomes. NoV-associated hospitalization rates were higher, more severe, resulted in longer stays and incurred greater costs than for younger patients. NoV-associated mortality rates were approximately 200 % higher among individuals 65 years and older compared to <5 years. The burden of NoV among older adults is expected to rise along with societal aging and increased need for institutionalized care. NoV prevention in older adults, including potential vaccination, may significantly impact risk of severe illness

Assessment of preparation time with fully-liquid versus non-fully liquid paediatric hexavalent vaccines. A time and motion study

AbstractBackground and aimsSimplified vaccine preparation steps would save time and reduce potential immunisation errors. The aim of the study was to assess vaccine preparation time with fully-liquid hexavalent vaccine (DTaP-IPV-HB-PRP-T, Sanofi Pasteur MSD) versus non-fully liquid hexavalent vaccine that needs reconstitution (DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals).MethodsNinety-six Health Care Professionals (HCPs) participated in a randomised, cross-over, open-label, time and motion study in Belgium (2014). HCPs prepared each vaccine in a cross-over manner with a wash-out period of 3–5min. An independent nurse assessed preparation time and immunisation errors by systematic review of the videos. HCPs satisfaction and preference were evaluated by a self-administered questionnaire.ResultsAverage preparation time was 36s for the fully-liquid vaccine and 70.5s for the non-fully liquid vaccine. The time saved using the fully-liquid vaccine was 34.5s (p≤0.001). On 192 preparations, 57 immunisation errors occurred: 47 in the non-fully liquid vaccine group (including one missing reconstitution of Hib component), 10 in the fully-liquid vaccine group. 71.9% of HCPs were very or somewhat satisfied with the ease of handling of both vaccines; 66.7% and 67.7% were very or somewhat satisfied with speed of preparation in the fully-liquid vaccine and the non-fully liquid vaccine groups, respectively. Almost all HCPs (97.6%) stated they would prefer the use of the fully-liquid vaccine in their daily practice.ConclusionsPreparation of a fully-liquid hexavalent vaccine can be completed in half the time necessary to prepare a non-fully liquid vaccine. The simplicity of the fully-liquid hexavalent vaccine preparation helps optimise reduction of immunisation errors

Long-term antibody persistence in children after vaccination with the pediatric formulation of an aluminum-free virosomal hepatitis A vaccine

Background: The pediatric dose of the virosomal hepatitis A vaccine Epaxal (R), Epaxal (R) Junior, is safe and immunogenic in children from 1 to 17 years of age. The present study investigated the long-term immunogenicity of Epaxal (R) Junior. The standard doses of Epaxal (R) and aluminum-adsorbed hepatitis A vaccine (Havrix (R) Junior) were used as comparators. Methods: A total of 271 children who had completed a 0/6-month immunization schedule (priming and booster dose) participated in this follow-up study. Anti-hepatitis A virus (HAV) antibody levels were measured using a microparticle enzyme immunoassay (HAVAB 2.0 Quantitative; Abbott Diagnostics, Wiesbaden, Germany) starting at 18 months following the second dose, and then yearly until 66 months (ie, 5.5 years) after the second dose. Results: All subjects tested at Month 66 still had protective anti-HAV antibodies (>= 10 mIU/mL). Antibody titers were generally lower in subjects 1-7 years old than in subjects 8-17 years old and higher in females 11-17 years old than in males 11-17 years old. In addition, an age-dependent decay was observed, that is, antibody decreased more rapidly in younger than in older children. Conclusions: Vaccination of children with two doses of Epaxal (R) Junior confers a real-time protection of at least 5.5 years. This protection is estimated to last approximately 25 years. Younger children showed lower antibody titers and a faster antibody decline than older children. Additional follow-up studies are needed beyond 5.5 years to further assess the longterm immunogenicity of Epaxal (R) Junior

Long-term follow-up of HPV infection using urine and cervical quantitative HPV DNA testing

The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. This study investigated the use of urine samples, which can be collected by self-sampling at home, instead of cervical samples for follow-up of an HPV intervention trial. Eighteen initially HPV DNA-positive women participating in an HPV therapeutic vaccine trial were monitored during a three-year follow-up period. A total of 172 urine samples and 85 cervical samples were collected. We obtained a paired urine sample for each of the 85 cervical samples by recovering urine samples from six monthly gynaecological examinations. We performed a small pilot study in which the participating women used a urine collection device at home and returned their urine sample to the laboratory by mail. All samples were analyzed using quantitative real-time HPV DNA PCR. A good association (κ value of 0.65) was found between the presence of HPV DNA in urine and a subsequent cervical sample. Comparisons of the number of HPV DNA copies in urine and paired cervical samples revealed a significant Spearman rho of 0.676. This correlation was superior in women with severe lesions. The HPV DNA results of the small pilot study based on self-collected urine samples at home are consistent with previous and subsequent urine and/or cervical results. We demonstrated that urine sampling may be a valid alternative to cervical samples for the follow-up of HPV intervention trials or programs. The potential clinical value of urine viral load monitoring should be further investigated