Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1

BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node-specific ICAM-grabbing non-integrin (L-SIGN)), can interact with pathogens including HIV-1 and is expressed at the maternal-fetal interface, we hypothesized that it could influence MTCT of HIV-1. METHODS AND FINDINGS: To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011). CONCLUSION: These results suggest that DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission

Assessing the efficiency of mother-to-child HIV prevention in low- and middle-income countries using data envelopment analysis

AIDS is one of the most significant health care problems worldwide. Due to the difficulty and costs involved in treating HIV, preventing infection is of paramount importance in controlling the AIDS epidemic. The main purpose of this paper is to explore the potential of using Data Envelopment Analysis (DEA) to establish international comparisons on the efficiency of implementation of HIV prevention programmes. To do this we use data from 52 low- and middle-income countries regarding the prevention of mother-to-child transmission of HIV. Our results indicate that there is a remarkable variation in the efficiency of prevention services across nations, suggesting that a better use of resources could lead to more and improved services, and ultimately, prevent the infection of thousands of children. These results also demonstrate the potential strategic role of DEA for the efficient and effective planning of scarce resources to fight the epidemic

Antenatal HIV-1 RNA load and timing of mother to child transmission; a nested case-control study in a resource poor setting

<p>Abstract</p> <p>Objective</p> <p>To determine HIV-1 RNA load during the third trimester of pregnancy and evaluate its effect on <it>in utero </it>and intra-partum/postpartum transmissions in a breastfeeding population.</p> <p>Design</p> <p>A nested case-control study within a PMTCT cohort of antiretroviral therapy naive pregnant women and their infants.</p> <p>Methods</p> <p>A case was a mother who transmitted HIV-1 to her infant (transmitter) who was matched to one HIV-1 positive but non-transmitting mother (control).</p> <p>Results</p> <p>From a cohort of 691 pregnant women, 177 (25.6%) were HIV-1 positive at enrolment and from these 29 (23%) transmitted HIV-1 to their infants, 10 and 19 during <it>in utero </it>and intra-partum/postpartum respectively. Twenty-four mothers sero-converted after delivery and three transmitted HIV-1 to their infants. Each unit increase in log₁₀viral load was associated with a 178 cells/mm³and 0.2 g/dL decrease in TLC and hemoglobin levels, p = 0.048 and 0.021 respectively, and a 29% increase in the risk of transmission, p = 0.023. Intra-partum/postpartum transmitters had significantly higher mean viral load relative to their matched controls, p = 0.034.</p> <p>Conclusion</p> <p>Antenatal serum HIV-1 RNA load, TLC and hemoglobin levels were significantly associated with vertical transmission but this association was independent of transmission time. This finding supports the rationale for preventive strategies designed to reduce vertical transmission by lowering maternal viral load.</p

Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review

BACKGROUND: Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO. METHODS: We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials. RESULTS: 12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4, 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups. CONCLUSIONS: Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial

Autistic Disorder in Patients with Williams-Beuren Syndrome: A Reconsideration of the Williams-Beuren Syndrome Phenotype

International audienceBackground: Williams-Beuren syndrome (WBS), a rare developmental disorder caused by deletion of contiguous genes at 7q11.23, has been characterized by strengths in socialization (overfriendliness) and communication (excessive talkativeness). WBS has been often considered as the polar opposite behavioral phenotype to autism. Our objective was to better understand the range of phenotypic expression in WBS and the relationship between WBS and autistic disorder. Methodology: The study was conducted on 9 French individuals aged from 4 to 37 years old with autistic disorder associated with WBS. Behavioral assessments were performed using Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) scales. Molecular characterization of the WBS critical region was performed by FISH. Findings: FISH analysis indicated that all 9 patients displayed the common WBS deletion. All 9 patients met ADI-R and ADOS diagnostic criteria for autism, displaying stereotypies and severe impairments in social interaction and communication (including the absence of expressive language). Additionally, patients showed improvement in social communication over time. Conclusions: The results indicate that comorbid autism and WBS is more frequent than expected and suggest that the common WBS deletion can result in a continuum of social communication impairment, ranging from excessive talkativeness and overfriendliness to absence of verbal language and poor social relationships. Appreciation of the possible co-occurrence of WBS and autism challenges the common view that WBS represents the opposite behavioral phenotype of autism, and might lead to improved recognition of WBS in individuals diagnosed with autism

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field