CD8(+) T-cell-mediated immunity against malaria: a novel heterologous prime-boost strategy

Evaluation of: Rodriguez D, Gonzalez-Aseguinolaza G, Rodriguez JR et al. Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium. PLoS ONE 7(4), e34445 (2012). Recently, a vaccine against malaria was successfully tested in a human Phase III trial. The efficacy of this vaccine formulation, based on the Plasmodium falciparum circumsporozoite protein, was approximately 50% and correlated with the presence of antibodies specific to the infective stages of the malaria parasites. Different strategies are being pursued to improve vaccine efficacy levels. One such strategy is the induction of specific cytotoxic T cells that can destroy the intracellular hepatocyte stages of the malaria parasite. In this study, a novel vaccination protocol was developed to elicit strong immune responses mediated by CD8(+) cytotoxic cells specific to the circumsporozoite protein. As proof-of-concept, the authors used the rodent malaria Plasmodium yoelii parasite. The vaccination strategy consisted of a heterologous prime-boost vaccination regimen involving porcine parvovirus-like particles for priming and the modified vaccinia virus Ankara for the booster immunization, both of which expressed the immunodominant CD8 epitope of the P. yoelii circumsporozoite protein. Results from this experimental model were extremely meaningful. This vaccination strategy led to a significant T-cell immune response mediated by CD8(+) multifunctional T effector and effector-memory cells. However, most importantly for the malaria vaccine development was the fact that following a sporozoite challenge, immunized mice eliminated more than 97% of the malaria parasites during the hepatocyte stages. These results confirm and extend a vast body of knowledge showing that a heterologous prime-boost vaccination strategy can elicit strong CD8(+) T-cell-mediated protective immunity and may increase the efficacy of malaria vaccines.

Awareness and knowledge of HPV, cervical cancer, and vaccines in young women after first delivery in São Paulo, Brazil - a cross-sectional study

Abstract Background The success of HPV vaccination programs will require awareness regarding HPV associated diseases and the benefits of HPV vaccination for the general population. The aim of this study was to assess the level of awareness and knowledge of human papillomavirus (HPV) infection, cervical cancer prevention, vaccines, and factors associated with HPV awareness among young women after birth of the first child. Methods This analysis is part of a cross-sectional study carried out at Hospital Maternidade Leonor Mendes de Barros, a large public maternity hospital in Sao Paulo. Primiparous women (15-24 years) who gave birth in that maternity hospital were included. A questionnaire that included questions concerning knowledge of HPV, cervical cancer, and vaccines was applied. To estimate the association of HPV awareness with selected factors, prevalence ratios (PR) were estimated using a generalized linear model (GLM). Results Three hundred and one primiparous women were included; 37% of them reported that they "had ever heard about HPV", but only 19% and 7%, respectively, knew that HPV is a sexually transmitted infection (STI) and that it can cause cervical cancer. Seventy-four percent of interviewees mentioned the preventive character of vaccines and all participants affirmed that they would accept HPV vaccination after delivery. In the multivariate analysis, only increasing age (P for trend = 0.021) and previous STI (P < 0.001) were factors independently associated with HPV awareness ("had ever heard about HPV"). Conclusions This survey indicated that knowledge about the association between HPV and cervical cancer among primiparous young women is low. Therefore, these young low-income primiparous women could benefit greatly from educational interventions to encourage primary and secondary cervical cancer prevention programs.

Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients

Background Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. Methods Surveillance of respiratory viruses was conducted in JIA patients during ARI season (March to August) in two consecutive years: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. Results During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. Conclusion ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients.

PReS-FINAL-2177: Safety and lack of autoantibody production following influenza H1N1 vaccination in patients with juvenile idiopathic arthritis (JIA)

Introduction Vaccination is an effective tool against several infectious agents including influenza. In 2010, the Advisory Committee on Immunization Practices (ACIP) recommended influenza A H1N1/2009 immunization for high risk groups, including juvenile idiopathic arthritis (JIA) patients and more recently the EULAR task force reinforced the importance of vaccination in immunosuppressed pediatric rheumatologic patients. We have recently shown that Influenza A H1N1/2009 vaccination generated protective antibody production with short-term safety profile among 93 JIA patients, but the possible impact of the vaccine in autoimmune response in JIA have not been studied. Therefore, we aimed to assess the production of some autoantibodies generated following influenza H1N1 vaccination in JIA patients. Objectives To assess the autoimmune response and H1N1 serology following influenza H1N1 vaccination in patients with JIA. Methods Cepa A/California/7/2009 (NYMC X-179A) anti-H1N1 was used to vaccinate JIA patients: 1 dose of immunization was given to all participants and those <9yrs of age received a second booster 3 weeks apart. Sera were analyzed before and 3 weeks following complete vaccination. Serology against H1N1 virus was performed by hemagglutination inhibition antibody assay, rheumatoid factor (RF) by latex fixation test, antinuclear antibodies (ANA) by IIF, IgM and IgG anticardiolipin (aCL) by ELISA.Results Among 98 JIA patients that were vaccinated, 58 sera were available for this study. Mean age of 58 JIA patients was 23.9 ± 9.5 yrs, 38 were females and 20 males with mean disease duration of 14.7 ± 10.1 yrs. JIA subtypes were: 33 (57%) poliarticular, 10 (17%) oligoarticular, 6 (10%) systemic and 9 (16%) other. Sixteen patients were off drugs while 42 (72%) were under different pharmacotherapy: 32 (55%) were on 1 DMARD/IS, 10 (17%) on 2 DMARDs/IS, 19 (33%) antimalarials, 29 (50%) MTX, 8(14%) sulfasalazine, 6 (10%) anti-TNFs, 4 (7%) abatacept; no patient was using prednisone >0.5 mg/kg/d. Seroprotection rates against H1N1 influenza increased from 23 to 83% and seroconversion rates were achieved in 78% JIA. Prior to vaccination, 31(53.4%) JIA patients were ANA+, 6(10.3%) RF+, and 4 (7%) IgM + IgG aCL+. After complete H1N1 vaccination, positivity for ANA remained the same whereas 1 patient became negative for IgG aCL, and another for RF, IgM and IgG aCL. One (1.7%) patient turned low titer IgG aCL+. Conclusion Vaccination of JIA patients against pandemic influenza A (H1N1) generated successful protective antibody production without the induction of autoantibody production, except for 1 patient that became positive for low titer IgG aCL, supporting its safety.

Bicistronic DNA vaccines simultaneously encoding HIV, HSV and HPV antigens promote CD8⁺ T cell responses and protective immunity

Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8⁺ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8⁺ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.

Immunogenicity and Reactogenicity of 2009 Influenza A (H1N1) Inactivated Monovalent Non-Adjuvanted Vaccine in Elderly and Immunocompromised Patients

Background Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them. Methods This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination. Results 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included. The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events. Conclusions The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)

Influenza della variabilità spaziale sul trasporto reattivo

La tesi ha per obiettivo di quantificare gli effetti che la variabilità spaziale del mezzo poroso ha sull'evoluzione di un sistema geochimico. Le reazioni di dissoluzione o precipiazione di minerali modificano la struttura microscopica del mezzo, e con essa le proprietà idrodinamiche del sistema, la permeabilità in modo particolare. La variabilità spaziale iniziale del mezzo può essere causa della formazione di digitazioni o canalizzazioni? La prima parte della tesi tratta il cambiamento di scala, necessario per passare da una simulazione geostatistica su griglia fine al calcolo di trasporto su una tessellazione più grossolana. Nel caso del codice di calcolo Hytec, che implementa uno schema ai volumi finiti basato su discretizzazione in poligoni di Voronoï, sono stati confrontati diversi metodi di calcolo della permeabilità equivalente, seguendo differenti criteri. La seconda parte riguarda i calcoli di trasporto reattivo condotti su famiglie di simulazioni geostatistiche del mezzo; l'influenza della variabilità spaziale iniziale sull'evoluzione dei sistemi viene quantificata grazie ad opportune grandezze osservabili. Sono state studiate due reazioni distinte: un caso di dissoluzione, in maniera più approfondita, e più rapidamente un caso di precipitazione, il cui effetto complessivo è quello di riequilibrare il sistema.

L'influenza del sonno sull'andamento temporale della consolidazione delle abilità procedurali

Background: It is well known, since the pioneristic observation by Jenkins and Dallenbach (Am J Psychol 1924;35:605-12), that a period of sleep provides a specific advantage for the consolidation of newly acquired informations. Recent research about the possible enhancing effect of sleep on memory consolidation has focused on procedural memory (part of non-declarative memory system, according to Squire’s taxonomy), as it appears the memory sub-system for which the available data are more consistent. The acquisition of a procedural skill follows a typical time course, consisting in a substantial practice-dependent learning followed by a slow, off-line improvement. Sleep seems to play a critical role in promoting the process of slow learning, by consolidating memory traces and making them more stable and resistant to interferences. If sleep is critical for the consolidation of a procedural skill, then an alteration of the organization of sleep should result in a less effective consolidation, and therefore in a reduced memory performance. Such alteration can be experimentally induced, as in a deprivation protocol, or it can be naturally observed in some sleep disorders as, for example, in narcolepsy. In this research, a group of narcoleptic patients, and a group of matched healthy controls, were tested in two different procedural abilities, in order to better define the size and time course of sleep contribution to memory consolidation. Experimental Procedure: A Texture Discrimination Task (Karni & Sagi, Nature 1993;365:250-2) and a Finger Tapping Task (Walker et al., Neuron 2002;35:205-11) were administered to two indipendent samples of drug-naive patients with first-diagnosed narcolepsy with cataplexy (International Classification of Sleep Disorder 2nd ed., 2005), and two samples of matched healthy controls. In the Texture Discrimination task, subjects (n=22) had to learn to recognize a complex visual array on the screen of a personal computer, while in the Finger Tapping task (n=14) they had to press a numeric sequence on a standard keyboard, as quickly and accurately as possible. Three subsequent experimental sessions were scheduled for each partecipant, namely a training session, a first retrieval session the next day, and a second retrieval session one week later. To test for possible circadian effects on learning, half of the subjects performed the training session at 11 a.m. and half at 17 p.m. Performance at training session was taken as a measure of the practice-dependent learning, while performance of subsequent sessions were taken as a measure of the consolidation level achieved respectively after one and seven nights of sleep. Between training and first retrieval session, all participants spent a night in a sleep laboratory and underwent a polygraphic recording. Results and Discussion: In both experimental tasks, while healthy controls improved their performance after one night of undisturbed sleep, narcoleptic patients showed a non statistically significant learning. Despite this, at the second retrieval session either healthy controls and narcoleptics improved their skills. Narcoleptics improved relatively more than controls between first and second retrieval session in the texture discrimination ability, while their performance remained largely lower in the motor (FTT) ability. Sleep parameters showed a grater fragmentation in the sleep of the pathological group, and a different distribution of Stage 1 and 2 NREM sleep in the two groups, being thus consistent with the hypothesis of a lower consolidation power of sleep in narcoleptic patients. Moreover, REM density of the first part of the night of healthy subjects showed a significant correlation with the amount of improvement achieved at the first retrieval session in TDT task, supporting the hypothesis that REM sleep plays an important role in the consolidation of visuo-perceptual skills. Taken together, these results speak in favor of a slower, rather than lower consolidation of procedural skills in narcoleptic patients. Finally, an explanation of the results, based on the possible role of sleep in contrasting the interference provided by task repetition is proposed.

Influenza delle caratteristiche quali-quantitative della luce da fonti artificiali sulla fisio-morfologia di piante verdi per interior landscaping

La conoscenza delle esigenze luminose (intensità, spettro, durata minima, massima ed ottimale del fotoperiodo di illuminazione) e della tolleranza alle condizioni degli interni delle piante ad uso decorativo, è di fondamentale importanza per una giusta tecnica di progettazione (dimensionamento e dislocazione dei punti luce) dell’indoor plantscaping. Il lungo periodo di condizionamento al quale queste piante vengono sottoposte, caratterizzato principalmente dalla scarsa disponibilità di luce naturale e dagli alti livelli di concentrazione di CO2 determina una forte influenza sui processi morfo-fisiologici. Il presente studio analizza il fattore luminoso ed è articolato su più punti quali; • caratterizzazione della riposta fotosintetica all’intensità luminosa di 21 delle principali specie a fogliame decorativo comunemente utilizzate nella realizzazione degli spazi verdi indoor, per stabilire quali siano i minimi ed ottimali livelli di PAR tali da garantire una fotosintesi netta positiva e nel complesso le condizioni di maggior benessere per le piante; • quantificazione dell’incremento fotosintetico netto dovuto ad una maggior concentrazione di CO2 negli interni rispetto alla concentrazione CO2 atmosferica esterna, all’aumentare dell’ intensità luminosa artificiale sulle precedenti specie; • monitoraggio dell’andamento delle attività fotosintetiche durante il periodo di illuminazione di 8 ore comunemente utilizzato in un interno ad uso lavorativo, a PAR costante e variabile in Ficus elastica e Dieffenbachia picta, al fine di stabilire quali possano essere le durate e le modalità di somministrazione della luce per rendere massima la fotosintesi netta riducendo al minimo i consumi energetici dovuti all’accensione delle lampade; • valutazione della risposta morfo-fisiologica e fotosintetica a modificazioni dello spettro luminoso mediante l’uso di LED monocromatici colorati ad emissione nel bianco, blu e rosso in Ficus benjamina e Iresine herbistii al fine di stabilire se questo tipo di lampade possano essere utilizzate come fonte integrativa e/o sostitutiva nella realizzazione degli spazi verdi interni. Vengono analizzati il punto si compensazione alla luce (g), il punto di saturazione alla luce (s), l’efficienza quantica (AQE), il punto di respirazione al buio (Rd) e la fotosintesi netta massima (A max) per (Aglaonema commutatum, Asplenium nidus, Anthurium andreanum, Begonia rex, Calathea luoise, Calathea veitchiana, Calathea rufibarba, Calathea zebrina, Codiaeum variegatum, Cthenanthe oppenheimiana, Dieffenbakia picta, Ficus benjamina, Ficus elatica, Ficus longifolia, Fittonia verschaffeltii, Iresine herbistii, Philodendron erubescens, Philodendron pertusum, Potos aureus, Spathiphillum wallisi, Syngonium podophillum ) e classificate le specie in funzione di Amax in quattro categorie; A max < 2 µmol CO2 m-2 s-1, A max compresa tra 2 e 4 µmol CO2 m-2 s-1, Amax cpmpresa tra 4 e 6 µmol CO2 m-2 s-1, Amax > 6 µmol CO2 m-2 s-1, al fine di mettere in risalto la potenzialità fotosintetiche di ogni singola specie. I valori di PAR compresi tra (g) ed (s) forniscono le indicazioni sulle quali basarsi per scegliere una giusta lampada o dimensionare un punto luce per ogni singola specie e/o composizione. È stimata l’influenza di due livelli di concentrazione di CO2 ambientale (400 e 800 ppm) all’incrementare dell’intensità luminosa sul processo fotosintetico delle specie precedenti. Per quasi tutte le specie 800 ppm di CO2 non favoriscono nessun incremento all’attività fotosintetica ad eccezione di Ficus benjamina, Ficus elatica e Syngonium podophillum se non accompagnati da una disponibilità luminosa superiore alle 10 µmol m-2 s-1. Viene monitorato l’andamento dell’attività fotosintetica a PAR costante e variabile (intervallando periodi di 8 minuti a PAR 40 e 80) durante 8 ore di illuminazione su Ficus elastica e Dieffenbachia picta al fine di stabilire la miglior modalità di somministrazione della luce. La fotosintesi netta cumulativa per l’intera durata di illuminazione a PAR costante mostra un calo dopo alcune ore dall’attivazione in Dieffenbackia, e un andamento oscillatorio in Ficus. L’illuminazione alternata consente di raggiungere i quantitativi di CO2 organicata a 80 µmol m-2 s-1 di PAR, dopo 5 ore e mezza sia in Ficus che Dieffenbackia sebbene le potenzialità fotosintetiche delle due piante siano molto differenti. È stato valutato l’effetto dell’illuminazione artificiale mediante LED (15W) a luce bianca, blu e rossa monocromatica in rapporto alla luce neon(36W) bianca tradizionale (con differenti abbinamenti tra le lampade) sui principali parametri morfologici e fisiologici, in Ficus benjamin ‘Variegata’ e Iresine herbistii per verificare se tali fonti possono rappresentare una valida alternativa nella sostituzione o integrazione di altre lampade per gli spazi verdi indoor. Tutte le combinazioni LED indagate possono rappresentare un’alternativa di sostituzione alla coltivazione con neon ed un risparmio energetico di oltre il 50%. Una PAR di 20,6 µmol m-2 s-1 della singola lampada LED bianco è sufficiente per mantenere la pianta in condizioni di sopravvivenza con un consumo di 15W a fronte dei 36W necessari per il funzionamento di ogni neon. La combinazione LED bianco + LED blu monocromatico favorisce il contenimento della taglia della pianta, caratteristica gradita nella fase di utilizzo indoor, una maggior produzione di sostanza secca e un’attività fotosintetica più elevata.