Trace element phytoextraction from contaminated soil: a case study under Mediterranean climate

Abstract

The current field study aims to assess the suitability of four different plant species (i.e. poplar, willow, hemp and alfalfa) to be used for trace element (TE) (i.e. Cd, Cu, Ni, Pb and Zn) phytoextraction under hot-arid Mediterranean climate conditions. Plants were grown for two consecutive years on a moderate TE contaminated soil, supplied with water and mineral nutrients. The growth and physiological parameters were assessed throughout the trial to compare the response of plants to the environmental pollution, and TE uptake rates were measured for aboveground plant tissues. The phytoextraction rate for each species was expressed as a function of aboveground biomass yield and the TE uptake and translocation within the plant. Alfalfa played a significant role in reducing extractable Ni (60.6%) and Zn (46%) in the soil, whereas hemp reduced 32% of extractable Cd and 46% of extractable Pb; poplar decreased extractable Cd (37%), Ni (49%), Pb (46%) and Zn (63%); and willow reduced the extractable Zn (73%) compared to the beginning of the trial. No change in total TE content was observed; however, poplar and willow were able to extract and accumulate the highest amount of Zn (3200 and 5200 g ha⁻¹ year⁻¹ respectively) and Cu (182 and 116 g ha⁻¹ year⁻¹), whereas hemp, with 36 g ha⁻¹ year⁻¹, showed the best phytoextraction potential for Pb. Overall, we found a positive correlation between the phytoextraction rate and biomass yield, extractable TE concentration and translocation factor (TF) and a negative relationship with Ca concentration in the soil.

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Therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss: an evaluator-blinded, split-scalp study

Abstract

Laser- or light-assisted therapies have been used to improve the perifollicular environment by upregulating the expression of growth factors and signaling molecules for hair restoration. The aim of our study was to preclinically and clinically evaluate the therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss (PHL). An in vivo hairless mouse study and an in vivo human skin environmental scanning electron microscopy (ESEM) study were performed with different power and energy settings. Thereafter, an evaluator-blinded, split-scalp study was conducted to evaluate hair thickness and density in 10 PHL patients treated with 12 sessions of fractionated thulium laser treatment with or without post-laser treatment application of a growth factor-containing (GF) solution. In in vivo hairless mouse skin, inverted cone-shaped zones of thulium laser-induced tissue coagulation (LITC) were noted immediately after treatment in the epidermis and upper to mid-dermis without remarkable ablative tissue injury. The ESEM study revealed round to oval-shaped zones of non-ablative LITC on the surface of the stratum corneum of a human subject immediately after laser irradiation. In PHL patients, 12 sessions of thulium laser monotherapy at 1-week intervals resulted in significantly increased hair density and thickness. Post-laser treatment application of GF solution offered additional therapeutic efficacy by improving hair density and thickness on the split scalp. The use of a fractionated thulium laser with or without post-laser therapy application of GF solution to treat PHL elicited remarkable improvements in hair thickness and hair counts.

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A combined carrier-adjuvant system of peptide nanofibers and toll-like receptor agonists potentiates robust CD8+ T cell responses

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Jai S. Rudra, Brianne N. Banasik, Gregg N. Milligan
Improving CD8+ T cell responses activated by subunit vaccination is crucial for improving vaccine efficacy and safety. Here we report a carrier-adjuvant system composed of self-assembling peptide nanofibers presenting an immunodominant antigen from herpes simplex virus (HSV) and toll-like receptor (TLR) agonists that induces robust effector and memory CD8+ T cell responses in mice. The effector function of vaccine-induced CD8+ T cells was influenced by the type of TLR agonist. The use of CpG (TLR9 agonist) resulted in significantly greater specific in vivo cytotoxicity and trended towards more cells producing both IFN-γ and TNF-α compared to gardiquimod (TLR7 agonist). Prime-boost immunization with peptide nanofibers combined with either adjuvant resulted in development of HSV-specific CD8+ memory T cells further demonstrating the capability of the carrier-adjuvant system to induce strong HSV-specific CD8+ T cell responses. Inclusion of peptide epitope-nanofibers in protein-based subunit vaccines should increase the functional spectrum of the vaccine-elicited immune response and protection.



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Meeting report: Global vaccine and immunization research forum

Publication date: Available online 12 January 2018
Source:Vaccine
Author(s): Andrew Q. Ford, Nancy Touchette, B. Fenton Hall, Angela Hwang, Joachim Hombach
Building on the success of the first Global Vaccine and Immunization Research Forum (GVIRF), the World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health in the United States of America, and the Bill & Melinda Gates Foundation convened the second GVIRF in March 2016. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific advances and innovative technologies to design and deliver vaccines as well as novel tools and approaches to increase the uptake of vaccines throughout the world. This report summarizes the discussions and conclusions from the forum participants.



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How close are countries of the WHO European Region to achieving the goal of vaccinating 75% of key risk groups against influenza? Results from national surveys on seasonal influenza vaccination programmes, 2008/2009 to 2014/2015

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Pernille Jorgensen, Jolita Mereckiene, Suzanne Cotter, Kari Johansen, Svetla Tsolova, Caroline Brown
BackgroundInfluenza vaccination is recommended especially for persons at risk of complications. In 2003, the World Health Assembly urged Member States (MS) to increase vaccination coverage to 75% among older persons by 2010.ObjectiveTo assess progress towards the 2010 vaccination goal and describe seasonal influenza vaccination recommendations in the World Health Organization (WHO) European Region.MethodsData on seasonal influenza vaccine recommendations, dose distribution, and target group coverage were obtained from two sources: European Union and European Economic Area MS data were extracted from influenza vaccination surveys covering seven seasons (2008/2009–2014/2015) published by the Vaccine European New Integrated Collaboration Effort and European Centre for Disease Prevention and Control. For the remaining WHO European MS, a separate survey on policies and uptake for all seasons (2008/2009–2014/2015) was distributed to national immunization programmes in 2015.ResultsData was available from 49 of 53 MS. All but two had a national influenza vaccination policy. High-income countries distributed considerably higher number of vaccines per capita (median; 139.2 per 1000 population) compared to lower-middle-income countries (median; 6.1 per 1000 population). Most countries recommended vaccination for older persons, individuals with chronic disease, healthcare workers, and pregnant women. Children were included in < 50% of national policies. Only one country reached 75% coverage in older persons (2014/2015), while a number of countries reported declining vaccination uptake. Coverage of target groups was overall low, but with large variations between countries. Vaccination coverage was not monitored for several groups.ConclusionsDespite policy recommendations, influenza vaccination uptake remains suboptimal. Low levels of vaccination is not only a missed opportunity for preventing influenza in vulnerable groups, but could negatively affect pandemic preparedness. Improved understanding of barriers to influenza vaccination is needed to increase uptake and reverse negative trends. Furthermore, implementation of vaccination coverage monitoring is critical for assessing performance and impact of the programmes.



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Outsmart HPV: Acceptability and short-term effects of a web-based HPV vaccination intervention for young adult gay and bisexual men

Publication date: Available online 10 January 2018
Source:Vaccine
Author(s): Annie-Laurie McRee, Abigail Shoben, Jose A. Bauermeister, Mira L. Katz, Electra D. Paskett, Paul L. Reiter
BackgroundEffective interventions to promote human papillomavirus (HPV) vaccination are needed, particularly among populations at increased risk of HPV-related disease. We developed and pilot tested a web-based intervention, Outsmart HPV, to promote HPV vaccination among young gay and bisexual men (YGBM).MethodsIn 2016, we recruited a national sample (n = 150) of YGBM ages 18–25 in the United States who had not received any doses of HPV vaccine. Participants were randomized to receive either standard HPV vaccination information (control) or population-targeted, individually-tailored content (Outsmart HPV intervention). We assessed between group differences in HPV vaccination attitudes and beliefs immediately following the intervention using multiple linear regression.ResultsThere were no differences in HPV vaccination attitudes, beliefs and intentions between groups at baseline. Compared to participants in the control group, intervention participants reported: greater perception that men who have sex with men are at higher risk for anal cancer relative to other men (b = 0.34); greater HPV vaccination self-efficacy (b = 0.15); and fewer perceived harms of HPV vaccine (b = −0.34) on posttest surveys (all p < .05). Overall, intervention participants reported high levels of acceptability and satisfaction with the Outsmart HPV intervention (all > 4.4 on a 5-point scale).ConclusionsFindings from this study provide preliminary support for a brief, tailored web-based intervention in improving HPV vaccination attitudes and beliefs among YGBM. An important next step is to determine the effects of Outsmart HPV on HPV vaccine uptake.Clinical trials registrationClinicalTrials.gov identifier NCT02835755.



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Pre-vaccine plasma levels of soluble inflammatory indices negatively predict responses to HAV, HBV, and tetanus vaccines in HCV and HIV infection

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Carey L. Shive, Chelsey J. Judge, Brian Clagett, Robert C. Kalayjian, Melissa Osborn, Kenneth E. Sherman, Carl Fichtenbaum, Rajesh T. Gandhi, Minhee Kang, Daniel L. Popkin, Scott F. Sieg, Michael M. Lederman, Benigno Rodriguez, Donald D. Anthony
BackgroundChronic hepatitis C virus (HCV) and HIV infections are associated with impaired responses to neo-antigens contained in hepatitis A virus (HAV)/hepatitis B virus (HBV) vaccines, yet responsible mechanisms are unclear.MethodsACTG 5232 and CFAR0910 were clinical trials where pre-vaccine levels of plasma IP10, IL-6, sCD163 and sCD14 were measured in viremic HCV- (n = 15) or HIV-infected participants (n = 24) and uninfected controls (n = 10). Accelerated dosing HAV/HBV vaccine and tetanus booster were administered and antibody response was measured at 0, 1, 3, 8, and 24 weeks.ResultsPre-vaccine plasma IP10, IL-6, and sCD14 levels were elevated in both HCV and HIV-infected participants, while sCD163 was also elevated in HCV-infected participants. Pre-immunization tetanus antibody levels were lower in HIV-infected than in uninfected participants, while vaccine induced antibody responses were intact in HCV and HIV-infected participants. After HAV/HBV vaccination, HCV and HIV-infected participants had lower and less durable HAV and HBV antibody responses than uninfected controls.Among HCV-infected participants, pre-vaccine plasma IP10, IL-6, sCD14, and sCD163 levels inversely correlated with HAV, HBV and tetanus antibody responses after vaccine. Low HAV/HBV vaccine responses in HIV-infected participants prohibited assessment of immune correlates.ConclusionsDuring HCV and HIV infection markers of systemic inflammation reflect immune dysfunction as demonstrated by poor response to HAV/HBV neo-antigen vaccine.



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Parent perceptions of dentists’ role in HPV vaccination

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Gabriela E. Lazalde, Melissa B. Gilkey, Melanie L. Kornides, Annie-Laurie McRee
IntroductionOffering HPV vaccine in settings beyond the traditional medical home holds promise for increasing the currently low levels of coverage. As adolescents frequently visit dentists, dental practices may be one such alternative vaccination setting. This study assessed parent attitudes about the roles dental providers could play in HPV prevention, including vaccine provision.MethodsIn September 2016, we conducted an online survey using a national sample (n = 1209) of U.S. parents of adolescent children aged 11–17. Adolescents' mean age was 14; 53% were male and 62% were non-Hispanic white. We identified correlates of parents' comfort with dentists as HPV vaccinators using multivariable logistic regression.ResultsOverall, 23% of parents reported that they would feel comfortable with their child receiving HPV vaccine from a dentist. In multivariable analyses, parents had greater odds of being comfortable if they had higher trust in their child's primary care provider (OR = 1.27, 95% CI: 0.96–1.68) and lower odds if their child was female (OR = 0.65, 95% CI: 0.50–0.86). Convenience (20%) and oral health expertise (20%) were the most commonly cited benefits of dentists administering the vaccine. Wanting their child's regular provider to administer and track vaccinations (61% and 58%, respectively), and lack of insurance coverage (30%) were the most commonly cited concerns. Parents expressed somewhat greater comfort with roles dentists might play in promoting HPV vaccination other than vaccine delivery, such as providing education.ConclusionsParents in this sample had low comfort with dentists as HPV vaccinators. Findings from this study highlight potential concerns to be addressed before dental practices consider offering HPV vaccination in the future. Further research should assess dentists' perspectives and explore alternative roles for dental providers in HPV prevention efforts.



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Editorial Board/Aims and Scope

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4





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Burden of medically attended influenza infection and cases averted by vaccination – United States, 2013/14 through 2015/16 influenza seasons

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Michael L. Jackson, C. Hallie Phillips, Joyce Benoit, Lisa A. Jackson, Manjusha Gaglani, Kempapura Murthy, Huong Q. McLean, Edward A. Belongia, Ryan Malosh, Richard Zimmerman, Brendan Flannery
BackgroundIn addition to preventing hospitalizations and deaths due to influenza, influenza vaccination programs can reduce the burden of outpatient visits for influenza. We estimated the incidence of medically-attended influenza at three geographically diverse sites in the United States, and the cases averted by vaccination, for the 2013/14 through 2015/16 influenza seasons.MethodsWe defined surveillance populations at three sites from the United States Influenza Vaccine Effectiveness Network. Among these populations, we identified outpatient visits laboratory-confirmed influenza via active surveillance, and identified all outpatient visits for acute respiratory illness from healthcare databases. We extrapolated the total number of outpatient visits for influenza from the proportion of surveillance visits with a positive influenza test. We combined estimates of incidence, vaccine coverage, and vaccine effectiveness to estimate outpatient visits averted by vaccination.ResultsAcross the three sites and seasons, incidence of medically attended influenza ranged from 14 to 54 per 1000 population. Incidence was highest in children aged 6 months to 9 years (33 to 70 per 1000) and lowest in adults aged 18–49 years (21 to 27 per 1000). Cases averted ranged from 9 per 1000 vaccinees (Washington, 2014/15) to 28 per 1000 (Wisconsin, 2013/14).DiscussionSeasonal influenza epidemics cause a considerable burden of outpatient medical visits. The United States influenza vaccination program has caused meaningful reductions in outpatient visits for influenza, even in years when the vaccine is not well-matched to the dominant circulating influenza strain.



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Serotype-specific immune responses to pneumococcal conjugate vaccine among children are significantly correlated by individual: Analysis of randomized controlled trial data

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Marc Lipsitch, Lucy M. Li, Scott Patterson, James Trammel, Christine Juergens, William C. Gruber, Daniel A. Scott, Ron Dagan
BackgroundThe magnitude of an individual's serotype-specific immunoglobulin G (IgG) response to a pneumococcal conjugate vaccine (PCV) has been associated with the vaccine's protective efficacy against carriage of pneumococci of that serotype, though the relationship with other serotypes needs to be understood.MethodsUsing immunogenicity data collected during a trial comparing the 7-valent (PCV7) and 13-valent (PCV13) vaccines, we measured associations between serotype-specific IgG levels, and used multiple regressions to identify demographic predictors of response.ResultsVaccine-induced IgG levels were moderately positively correlated with one another, with pairwise correlation coefficients of 0.40–0.70. Principal component analysis of vaccine-serotype responses yielded one principal component indicating general immune responsiveness, and a second principal component mainly describing responses to serotype 14, which was the least correlated with the other responses. Overall, demographic variables explained only 17.0 and 20.4% of the geometric mean PCV7 and PCV13 responses, respectively. In both groups, older age at the first vaccine dose and shorter time from vaccination to antibody measurement were independently associated with stronger geometric mean responses.DiscussionImproved understanding of the nature and causes of variation in immune response may aid in optimizing vaccination schedules and identifying robust correlates of protection.



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A novel inactivated vaccine against Lawsonia intracellularis induces rapid induction of humoral immunity, reduction of bacterial shedding and provides robust gut barrier function

Publication date: Available online 11 January 2018
Source:Vaccine
Author(s): F. Roerink, C.L. Morgan, S.M. Knetter, M.-H. Passat, A.L. Archibald, T. Ait-Ali, E.L. Strait
Porcine proliferative ileitis is a major economic burden for the swine industry, affecting growing pigs and young adult pigs. In this study, the protective efficacy of an inactivated, injectable whole-cell bacteria vaccine against L. intracellularis – Porcilis® Ileitis was evaluated under field conditions.Eighty-five, three-week-old pigs on a commercial farrow-to-finish farm were vaccinated by the intramuscular route, either with a dose of injectable vaccine, or with saline. A subset of vaccinates and control pigs were necropsied at 21 days post-challenge. Incidence and severity of ileitis were evaluated by gross and microscopic observation of ileal tissues. Colonization of the gut after challenge was examined by L. intracellularis-specific immunohistochemistry, and qPCR of ileal scrapings. Integrity of the intestinal barrier was evaluated to quantify a range of intestinal markers including secreted mucin and intestinal alkaline phosphatase, and innate immune markers including Caspase-3 and Calprotectin. A second subset of pigs was monitored for fecal shedding of L. intracellularis, until resolution of shedding.Our investigation indicated that Porcilis Ileitis provided robust protection against ileitis, reduced bacterial shedding 15-fold (p < .05) and preserved normal gut barrier function in the face of an experimental challenge with virulent L. intracellularis.



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Single-dose varicella vaccine effectiveness in Brazil: A case-control study

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Ana Lucia Andrade, Maria Aparecida da Silva Vieira, Ruth Minamisava, Cristiana Maria Toscano, Menira Borges de Lima Souza, Fabíola Fiaccadori, Cristina Adelaide Figueiredo, Suely Pires Curti, Maria Lígia Bacciotte Ramos Nerger, Ana Luiza Bierrenbach
BackgroundVaricella vaccine was introduced into the Brazilian Immunization Program in October 2013, as a single-dose schedule administered at 15 months of age. Its effectiveness had not yet been assessed in the country.MethodsA matched case-control study was carried out in São Paulo and Goiânia (Southeast and Midwest regions, respectively), Brazil. Suspected cases, were identified through a prospective surveillance established in the study sites. All cases had specimens from skin lesion collected for molecular laboratory testing. Cases were confirmed by either clinical or PCR of skin lesions and classified as mild, moderate, and severe disease.Two neighborhood controls were selected for each case. Cases and controls were aged 15–32 months and interviewed at home. Evidence of prior vaccination was obtained from vaccination cards. Univariate and multivariate logistic regression models were used, and odds ratio and its respective 95% confidence intervals were estimated. Vaccine effectiveness was estimated by comparing de odds of having received varicella vaccine among cases and controls.ResultsA total of 168 cases and 301 controls were enrolled. Moderate and severe illness, was found in 33.3% and 9.9% of the cases. Effectiveness of a single dose varicella vaccine was 86% (95%CI 72–92%) against disease of any severity and 93% (95%CI 82–97%) against moderate and severe disease. Out of 168 cases, 81.8% had positive PCR results for wild-type strains, and 22.0% were breakthrough varicella cases. Breakthrough cases were milder compared to non-breakthrough cases (p < .001).ConclusionsEffectiveness of single dose varicella vaccine in Brazil is comparable to that in other countries where breakthrough varicella cases have also been found to occur. The goal of the varicella vaccination program, along with disease burden and affordability should be taken into consideration when considering the adoption of a second dose of varicella vaccine into national immunization programs.



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Functionality and avidity of norovirus-specific antibodies and T cells induced by GII.4 virus-like particles alone or co-administered with different genotypes

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Maria Malm, Kirsi Tamminen, Suvi Heinimäki, Timo Vesikari, Vesna Blazevic
Norovirus (NoV) is the main cause of acute gastroenteritis worldwide across all age groups. Current NoV vaccine candidates are based on non-infectious highly immunogenic virus-like particles (VLPs) produced in cell cultures in vitro. As NoVs infecting human population are highly divergent, it is proposed that the vaccine should contain at least two different NoV genotypes, potentially affecting the immunogenicity of each other. We investigated the immunogenicity of NoV GII.4 VLPs administered by intramuscular (IM) or intradermal (ID) injections to BALB/c mice either alone or co-delivered with genogroup I (GI) and other genogroup GII VLPs. Serum NoV-specific IgG binding antibody titers and antibody functionality in terms of avidity and blocking potential were assessed. Furthermore, the specificity and functional avidity of CD4⁺ and CD8⁺ T cell responses were analyzed using synthetic peptides previously identified to contain NoV VP1 P2 domain-specific H-2^d epitopes. The results showed that IM and ID immunization induced comparable GII.4-specific antibodies and T cell responses. Similar magnitude and functionality of antibodies and interferon-gamma producing T cells were developed using monovalent GII.4 VLPs or different genotype combinations. For the first time, degranulation assay using multicolor flow cytometry showed that NoV GII.4-specific CD8⁺ T cells had cytotoxic T lymphocyte phenotype. To conclude, our results demonstrate that there is no immunological interference even if up to five different NoV VLP genotypes were co-administered at the same time. Furthermore, no inhibition of NoV-specific antibody functionality or the magnitude, specificity and affinity of T cell responses was observed in any of the immunized animals, observations relevant for the development of a multivalent NoV VLP vaccine.



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Willingness to accept a future influenza A(H7N9) vaccine in Beijing, China

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Shuangsheng Wu, Jianting Su, Peng Yang, Haiyan Zhang, Hongjun Li, Yanhui Chu, Weiyu Hua, Chao Li, Yaqing Tang, Quanyi Wang
BackgroundThe present study aimed to estimate residents' willingness to accept a future H7N9 vaccine and its determinants in the general adult population in Beijing, China.MethodsWe conducted a multi-stage sampling, cross-sectional survey using self-administered anonymous questionnaires from May to June, in 2014. The main outcome variable was residents' willingness to accept a future H7N9 vaccine. Logistic regression was used to identify the predictors of vaccination willingness.ResultsOf the 7264 eligible participants, 14.5% of Beijing residents reported that they had not heard of H7N9. Among those who had heard of H7N9, 59.5% of the general adult population would be willing to accept a future H7N9 vaccine, and approximately half of them reported 'I am afraid of being infected by H7N9' and 'H7N9 vaccine can prevent infections', and 28.1% reported 'my daily life is affected by H7N9'. The variables that were significantly associated with a higher likelihood of reporting willingness were being younger adults (aged 18–29 years: OR = 1.52, 95% CI: 1.17–1.97; aged 30–39 years: OR = 1.39, 95% CI: 1.08–1.78), being farmers (OR = 1.61; 95% CI: 1.32–1.96), being unemployed people (OR = 1.36; 95% CI: 1.04–1.78), living in suburban areas (OR = 2.18; 95% CI: 1.89–2.51), having ≥2 children in the family (OR = 1.41; 95% CI: 1.03–1.92), perceived risk in China (OR = 1.30; 95% CI: 1.15–1.48), perceived susceptibility to disease (OR = 3.13; 95% CI: 2.73–3.58), perceived negative effect on daily life (OR = 1.32; 95% CI: 1.13–1.55), perceived effectiveness of vaccination (OR = 2.34; 95% CI: 2.07–2.64), and recent uptake of influenza vaccine (OR = 2.26; 95% CI: 1.92–2.66).ConclusionsA great number of Beijing residents had doubts about the vaccine's effectiveness and were not concerned about disease risk, which were the factors affecting willingness to be vaccinated. Targeted education programs on disease risk as well as vaccine's effectiveness are needed to improve the willingness of vaccination for potential H7N9 pandemic preparedness.



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Bacillus Calmette-Guérin (BCG) vaccine: A global assessment of demand and supply balance

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Tania Cernuschi, Stefano Malvolti, Emily Nickels, Martin Friede
Over the past decade, several countries across all regions, income groups and procurement methods have been unable to secure sufficient BCG vaccine supply. While the frequency of stock-outs has remained rather stable, duration increased in 2014–2015 due to manufacturing issues and attracted the attention of national, regional and global immunization stakeholders. This prompted an in-depth analysis of supply and demand dynamics aiming to characterize supply risks. This analysis is unique as it provides a global picture, where previous analyses have focused on a portion of the market procuring through UN entities. Through literature review, supplier interviews, appraisal of shortages, stock-outs and historical procurement data, and through demand forecasting, this analysis shows an important increase in global capacity in 2017: supply is sufficient to meet forecasted BCG vaccine demand and possibly buffer market shocks. Nevertheless, risks remain mainly due to supply concentration and limited investment in production process improvements, as well as inflexibility in demand. Identification of these market risks will allow implementation of risk-mitigating interventions in three areas: (1) enhancing information sharing between major global health actors, countries and suppliers, (2) identifying interests and incentives to expand product registration and investment in the BCG manufacturing process, and (3) working with countries for tighter vaccine management.



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Declining measles antibodies in the era of elimination: Australia’s experience

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Heather F. Gidding, Helen E. Quinn, Linda Hueston, Dominic E. Dwyer, Peter B. McIntyre
BackgroundAustralia is one of only a few countries with a long-standing and consistent serosurveillance program. We conducted a national serosurvey in 2012–2013 to estimate population seroprevalence of measles-specific IgG and the effective reproduction number, R, and compare the results with the three previous serosurveys (1996–1999, 2002 and 2007) to examine trends following a decade of sustained measles control.Methods2729 residual sera from 1 to 49 year olds were tested using the Enzygnost anti-measles IgG enzyme immunoassay (EIA). All sera in the equivocal range by EIA on re-testing and a random sample of low positive and negative sera were later tested by a microneutralisation assay. R was calculated from weighted estimates of the proportion seronegative by age using a previously developed contact matrix.ResultsIn the 2012–13 serosurvey, anti-measles IgG seropositivity for 1–49 year olds was 80.8% (95% CI: 79.4–82.3%) and 8.9% (95% CI: 7.8–10.0%) had equivocal antibody levels. The increasing proportion of seronegative and equivocal individuals in age groups 10–39 years continued a trend seen in previous serosurveys. There was also an increase in equivocal results among 2–4 and 5–9 year old children, >90% of whom were recently vaccinated. R increased from 0.57 in 1999 to above the epidemic threshold of 1 in 2012–13 (R = 1.7). All 20 EIA negative sera, 238/241 (98.8%) equivocal sera, and 89/92 (96.7%) low positive sera had a titre <10 (negative) in the measles microneutralisation assay.ConclusionsA number of countries with sustained measles control have now demonstrated that measles-specific IgG antibodies decline with time since vaccination. As there is good epidemiologic evidence of population-level protection, the implications of declining measles-specific IgG antibody levels for maintaining measles elimination are unclear. Novel studies to determine correlates of protection against measles transmission and disease in the post-elimination era are needed to help answer this question.



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Immunization of preterm infants with GSK’s hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity

Publication date: Available online 12 January 2018
Source:Vaccine
Author(s): Felix Omeñaca, Liliana Vázquez, Pilar Garcia-Corbeira, Narcisa Mesaros, Linda Hanssens, Jan Dolhain, Ivonne Puente Gómez, Johannes Liese, Markus Knuf
BackgroundInfants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed.MethodsHere we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials.ResultsAt least 92.5% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13–30% of medically stable infants with history of prematurity developed apnea after vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens.ConclusionGSK's hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age.



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HIV population-level adaptation can rapidly diminish the impact of a partially effective vaccine

Publication date: 25 January 2018
Source:Vaccine, Volume 36, Issue 4
Author(s): Joshua T. Herbeck, Kathryn Peebles, Paul T. Edlefsen, Morgane Rolland, James T. Murphy, Geoffrey S. Gottlieb, Neil Abernethy, James I. Mullins, John E. Mittler, Steven M. Goodreau
BackgroundDevelopment of an HIV vaccine might be essential to ending the HIV/AIDS pandemic. However, vaccines can result in the emergence and spread of vaccine-resistant strains. Indeed, analyses of breakthrough infections in the HIV phase 3 vaccine trial RV144 identified HIV genotypes with differential rates of transmission in vaccine and placebo recipients. We hypothesized that, for HIV vaccination programs based on partially effective vaccines similar to RV144, HIV adaptation will rapidly diminish the expected vaccine impact.Methods and findingsUsing two HIV epidemic models, we simulated large-scale vaccination programs and, critically, included HIV strain diversity with respect to the vaccine response. We show here that rapid population-level viral adaptation can lead to decreased overall vaccine efficacy and substantially fewer infections averted by vaccination, when comparing scenarios with and without viral evolution (with outcomes depending on vaccination coverage, vaccine efficacy against the sensitive allele, and the initial resistant allele frequency). Translating this to the epidemic in South Africa, a scenario with 70% vaccination coverage may result in 250,000 infections (non-averted by vaccination) within 10 years of vaccine rollout that are due solely to HIV adaptation, all else being equal.ConclusionsThese findings suggest that approaches to HIV vaccine development, program implementation, and epidemic modeling may require attention to viral adaptation in response to vaccination.



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German travelers’ preferences for travel vaccines assessed by a discrete choice experiment

Publication date: Available online 12 January 2018
Source:Vaccine
Author(s): Christine Poulos, Desmond Curran, Anastassia Anastassopoulou, Laurence De Moerlooze
BackgroundMany travelers to regions with endemic infectious diseases do not follow health authorities' recommendations regarding vaccination against vaccine-preventable infectious diseases, before traveling. The determinants of individual travelers' decisions to vaccinate before traveling are largely unknown. This study aimed to provide this information using a discrete choice experiment (DCE) administered to four types of German travelers: (1) business travelers; (2) travelers visiting friends and relatives (VFR); (3) leisure travelers; and (4) backpackers.MethodsA DCE survey was developed, pretested and administered online. It included a series of choice questions in which respondents chose between two hypothetical vaccines, each characterized by four disease attributes with varying levels describing the of risk, health impact, curability and transmissibility of the disease they would prevent (described with four disease attributes with varying levels of risk, health impact, curability and transmissibility), and varying levels of four vaccine attributes (duration of protection, number of doses required, time required for vaccination, and vaccine cost). A random-parameters logit model was used to estimate the importance weights each traveler type placed on the various attribute levels. These weights were used to calculate mean monetary equivalents (MMEs) of changes in each attribute (holding all others constant) and of hypothetical disease-vaccine combinations.ResultsAll traveler types' choices indicated that they attached the greatest importance to the risk and health impact of disease and to the vaccine cost whereas the other disease and vaccine attributes were less important for their decisions about travel vaccines. An option of not choosing any of the vaccine-pairs presented was rarely selected indicating that travelers' generally prefer to be vaccinated rather than not. The MMEs of changes in vaccine attributes indicated a very high variability between the individual travelers within each type.ConclusionsThe travelers' responses indicated strong preferences for selecting vaccination rather than opting out of vaccination, and disease risk, health impact and vaccine cost were the most important features for vaccine choice.



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