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Boraschi D.,National Research Council Italy | Aguado M.T.,Initiative for Vaccine Research | Dutel C.,Fondation Merieux | Goronzy J.,Stanford University | And 4 more authors.
Science Translational Medicine | Year: 2013

Prolonged life expectancy in the 20th century has been one of humankind's greatest triumphs. However, the substantial increase in the human life span has ushered in a new concern: healthy aging. Because infectious diseases prominently contribute to morbidity in the particularly vulnerable elderly population, strategies for preventing these diseases would have a clear impact on improving healthy aging. Thus, vaccines and immunization strategies tailored for the elderly population are needed, and vaccines should be developed to take into consideration the peculiar age-induced variations of immune responsiveness. The conference "Ageing and Immunity" recently held in Siena, Italy, has reviewed and discussed several possible causes of immune senescence, as well as strategies for counteracting this waning of immune responsiveness and for restoring immunocompetence. In addition, examples of diseases that should be targeted by vaccination in the senior population were considered.


Steele A.D.,Initiative for Vaccine Research | Steele A.D.,University of Limpopo | Madhi S.A.,University of Witwatersrand | Louw C.E.,Madibeng Center for Research | And 7 more authors.
Pediatric Infectious Disease Journal | Year: 2011

Background: Rotavirus and human immunodeficiency virus (HIV) infections are a cause of great public health concern in developing countries. The current study evaluated the safety, reactogenicity, and immunogenicity of RIX4414 vaccine in asymptomatic or mildly symptomatic (clinical stages I and II according to WHO classification) HIV-infected South African infants. Methods: A total of 100 HIV-positive infants aged 6 to 10 weeks enrolled in this double-blind, 1:1 randomized, placebo-controlled study were allocated into 2 groups to receive 3 doses of RIX4414 vaccine/placebo according to a 0-, 1-, and 2-month schedule. Routine vaccines were concomitantly administered. Solicited and unsolicited symptoms were recorded for 15 and 31 days after each dose, respectively. Serious adverse events were recorded throughout the study period. Serum antirotavirus IgA concentrations (enzyme-linked immunosorbent assay, cut-off 20 U/mL) and the immunodeficiency status were determined at screening and 2 months post-Dose 3. Stool samples were analyzed for rotavirus using enzyme-linked immunosorbent assay at predetermined points and during diarrhea episodes. Results: All symptoms (solicited and unsolicited) occurred at a similar frequency in both groups. Six fatal serious adverse events in RIX4414 and 9 in placebo groups were reported. At 2 months post-Dose 3, the seroconversion rates were 57.1% (95% CI: 34-78.2) in RIX4414 and 18.2% (95% CI: 5.2-40.3) in the placebo group. The mean absolute CD4 cell count, CD4 percentage, and HIV-1 viral load were comparable in both groups at screening and 2 months post-Dose 3. Rotavirus shedding peaked at Day 7 after Dose 1 of RIX4414 with prolonged shedding was observed in 1 infant only. Conclusions: Three doses of RIX4414 vaccine was tolerated well by the South African HIV-positive infants. A satisfactory immune response was mounted without aggravating their immunologic or HIV condition. Copyright © 2011 by Lippincott Williams & Wilkins.


Jit M.,London School of Hygiene and Tropical Medicine | Jit M.,Public Health England | Brisson M.,Imperial College London | Brisson M.,Laval University | Hutubessy R.,Initiative for Vaccine Research
The Lancet Global Health | Year: 2014

Background: Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specific effects on health and economic costs. We aimed to develop and validate a simple generic model of such effects that could be used and understood in a range of settings with little external support. Methods: We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-effectiveness and health effects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine efficacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-effectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed differences between countries in terms of cost-effectiveness and health effects. Findings: In validation, PRIME reproduced cost-effectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690 000 cases of cervical cancer and 420 000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost effective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200 000 cases of cervical cancer and 100 000 deaths in some of the highest-burden countries. Interpretation: Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions. Funding: WHO. © 2014 World Health Organization.


Armah G.E.,University of Ghana | Sow S.O.,Center for Vaccine Development | Breiman R.F.,Centers for Disease Control and Prevention | Breiman R.F.,Kenya Medical Research Institute | And 24 more authors.
The Lancet | Year: 2010

Background: Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009. Methods: In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score ≥11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648. Findings: 5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610·6 person-years in the vaccine group, compared with 129 cases in 2585·9 person-years in the placebo group, resulting in a vaccine efficacy against severe rotavirus gastroenteritis of 39·3 (95 CI 19·1-54·7, p=0·0003 for efficacy >0). Median follow-up in both groups was 527 days starting 14 days after the third dose of vaccine or placebo was given. 42 (1·5) of 2723 infants assigned to receive vaccine and 45 (1·7) of 2724 infants assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was gastroenteritis (vaccine 17 [0·6]; placebo 17 [0·6]). Interpretation: Pentavalent rotavirus vaccine is effective against severe rotavirus gastroenteritis in the first 2 years of life in African countries with high mortality in infants younger than 5 years. We support WHO's recommendation for adoption of rotavirus vaccine into national expanded programmes on immunisation in Africa. © 2010 Elsevier Ltd.


Tam J.S.,Initiative for Vaccine Research | Barbeschi M.,Health Security and Environment Cluster | Shapovalova N.,Health Security and Environment Cluster | Briand S.,Health Security and Environment Cluster | And 3 more authors.
The Lancet Infectious Diseases | Year: 2012

Public health research is essential for the development of effective policies and planning to address health security and risks associated with mass gatherings (MGs). Crucial research topics related to MGs and their effects on global health security are discussed in this review. The research agenda for MGs consists of a framework of five major public health research directions that address issues related to reducing the risk of public health emergencies during MGs; restricting the occurrence of non-communicable and communicable diseases; minimisation of the effect of public health events associated with MGs; optimisation of the medical services and treatment of diseases during MGs; and development and application of modern public health measures. Implementation of the proposed research topics would be expected to provide benefits over the medium to long term in planning for MGs. © 2012 Elsevier Ltd.


Girard M.P.,French National Academy of Medicine | Katz J.M.,Centers for Disease Control and Prevention | Pervikov Y.,Initiative for Vaccine Research | Hombach J.,Initiative for Vaccine Research | Tam J.S.,Initiative for Vaccine Research
Vaccine | Year: 2011

On February 17-18, 2011, the World Health Organization convened the 7th meeting on " The Evaluation of Pandemic Influenza Vaccines in Clinical Trials" to review the progress made on pandemic A (H1N1) 2009 vaccines and the evaluation of their effectiveness in the field, especially in children less than 3 years of age and in pregnant women. Other topics to be addressed included a comparison of egg- and cell culture-based influenza vaccines, technical issues related to vaccine strain development and vaccine potency, and the status of development of prototype influenza vaccines using new technologies. Pandemic A (H1N1) vaccines were safe in young children, pregnant women and immunocompromized individuals. Overall effectiveness of inactivated A (H1N1) vaccines for all ages was found to vary between 72% and 100% in different countries and with different vaccine preparations. Effectiveness of pandemic A (H1N1) 2009 live attenuated vaccine was estimated to be approximately 80% in pediatric populations in the USA. A single dose of inactivated vaccine adjuvanted with AS03, MF59 or AF03 induced protective immunity in young children and pregnant women. However, unadjuvanted vaccines as well as low dose adjuvanted vaccines (1.9 μg HA) required two doses to elicit protective antibody levels in these populations. Clinical trials of influenza vaccines developed using new technologies showed they were well tolerated and induced antibody and/or T cell immune responses to viral proteins. Further studies are warranted to validate novel immunological criteria for evaluation and licensing of such new influenza vaccine concepts. On the regulatory side, work should be undertaken to harmonize the results of serological tests used to evaluate the immunogenicity of traditional influenza vaccines. © 2011.


Steele A.D.,PATH | Steele A.D.,Initiative for Vaccine Research | Patel M.,Centers for Disease Control and Prevention | Cunliffe N.A.,University of Liverpool | And 3 more authors.
Vaccine | Year: 2012

Rotavirus causes approximately 450,000 deaths annually among children less than 5 years of age worldwide, almost half of which occur in Africa. After the recent completion of successful trials of 2 new rotavirus vaccines, the World Health Organization has recommended these vaccines for all children worldwide. Because a previous rotavirus vaccine, Rotashield®, was associated with intussusception, a form of intestinal obstruction among infants, the current rotavirus vaccines were tested in large clinical trials and found to be safe. However, due to the past Rotashield® experience, post licensure monitoring of intussusception is considered to be crucial after the introduction of future oral rotavirus vaccines. Thus, in planning for future introductions of rotavirus vaccine in Africa, a workshop of experts working on intussusception was convened by the World Health Organization in May 2004 in association with the Pan-African Association of Paediatric Surgeons (PAPSA) in Malawi. In brief, delegates from ten countries presented data from retrospective record reviews of intussusception events from 1993 to 2003 at selected hospitals in their respective countries. This review showed that age of intussusception onset during infancy varies markedly with peak prevalence between 4 and 6 months of life. Diagnostic modality (e.g., contrast enema, ultrasound) was employed in <20% of the events; nearly 70% of the intussusception events were diagnosed at the time of surgery. Overall, case-fatality was high, ∼13%, in these African countries. The findings of this meeting highlight the challenges in implementing surveillance for intussusception after rotavirus vaccine introduction in Africa. The deliberations identified some concrete steps necessary to establish active surveillance at sentinel sites in African countries. This is becoming more urgent now that many countries are expressing interest in introducing rotavirus vaccines. © 2012.


PubMed | Centers for Disease Control and Prevention, Agence de Medecine Preventive, Sabin Vaccine Institute, London School of Hygiene and Tropical Medicine and 3 more.
Type: | Journal: Vaccine | Year: 2015

Pan American Health Organizations (PAHO) ProVac Initiative aims to strengthen countries technical capacity to make evidence-based immunization policy. With financial support from the Bill and Melinda Gates Foundation, PAHO established the ProVac International Working Group (IWG), a platform created for two years to transfer the ProVac Initiatives tools and methods to support decisions in non-PAHO regions.In 2011, WHO Regional Offices and partner agencies established the IWG to transfer the ProVac framework for new vaccine decision support, including tools and trainings to other regions of the world. During the two year period, PAHO served as the coordinating secretariat and partner agencies played implementing or advisory roles.Fifty nine national professionals from 17 countries received training on the use of economic evaluations to aid vaccine policy making through regional workshops. The IWG provided direct technical support to nine countries to develop cost-effectiveness analyses to inform decisions. All nine countries introduced the new vaccine evaluated or their NITAGs have made a recommendation to the Ministry of Health to introduce the new vaccine.Developing countries around the world are increasingly interested in weighing the potential health impact due to new vaccine introduction against the investments required. During the two years, the ProVac approach proved valuable and timely to aid the national decision making processes, even despite the different challenges and idiosyncrasies encountered in each region. The results of this work suggest that: (1) there is great need and demand for technical support and for capacity building around economic evaluations; and (2) the ProVac method of supporting country-owned analyses is as effective in other regions as it has been in the PAHO region.Decision support for new vaccine introduction in low- and middle-income countries is critical to guiding the efficient use of resources and prioritizing high impact vaccination programs.


Marchetti E.,Voltaire | Mazarin-Diop V.,Agence Africaine de Recherche en Sante Humaine | Chaumont J.,Voltaire | Martellet L.,Voltaire | And 4 more authors.
Vaccine | Year: 2012

Group A Neisseria meningitidis epidemics have been an important and unresolved public health problem in sub-Saharan Africa for over a century. The Meningitis Vaccine Project (MVP) was established in 2001 with the goal of developing, testing, licensing, and introducing an affordable group A meningococcal conjugate vaccine for Africa. A monovalent group A conjugate vaccine, MenAfriVac™, was developed at the Serum Institute of India Ltd. and tested in clinical trials at multiple trial sites in sub-Saharan African countries.The setup and successful conduct of ICH-GCP standard vaccine trials across multiple trial sites located in low-resource settings are challenging. We describe the main operational issues encountered in three randomized, observer-blind, active controlled studies to evaluate the safety and immunogenicity of MenAfriVac™. The studies were conducted in parallel among 2700 subjects aged between 2 months and 29 years of age enrolled across four trial sites located in Mali, The Gambia, Senegal, and Ghana between September 2006 and August 2009.Many important lessons were learned during the preparation, setup, and implementation of the Meningitis Vaccine Project clinical program. They are summarized here to help vaccine development programs identify efficient pathways for successful implementation of clinical trials in low-resource settings. © 2012 Elsevier Ltd.


Zaman K.,International Center for Diarrhoeal Disease Research | Anh D.D.,National Institute of Hygiene and Epidemiology | Victor J.C.,PATH | Shin S.,Korean International Vaccine Institute | And 15 more authors.
The Lancet | Year: 2010

Background: Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries, but no efficacy studies have been done in developing countries in Asia. We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam. Methods: In this multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab, Bangladesh, and urban and periurban Nha Trang, Vietnam, infants aged 4-12 weeks without symptoms of gastrointestinal disorders were randomly assigned (1:1) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age, in conjunction with routine infant vaccines including oral poliovirus vaccine. Randomisation was done by computer-generated randomisation sequence in blocks of six. Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent recollection. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score ≥11) arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648. Findings: 2036 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=1018) or placebo (n=1018). 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per-protocol analysis. Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days (IQR 480-575). 38 cases of severe rotavirus gastroenteritis (Vesikari score ≥11) were reported during more than 1197 person-years of follow up in the vaccine group, compared with 71 cases in more than 1156 person years in the placebo group, resulting in a vaccine efficacy of 48·3 (95 CI 22·3-66·1) against severe disease (p=0·0005 for efficacy >0) during nearly 2 years of follow-up. 25 (2·5) of 1017 infants assigned to receive vaccine and 20 (2·0) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was pneumonia (vaccine 12 [1·2]; placebo 15 [1·5]). Interpretation: In infants in developing countries in Asia, pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis, and our results support expanded WHO recommendations to promote its global use. © 2010 Elsevier Ltd.

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