Benefits of Peanut Consumption While Breastfeeding

Benefits of Peanut Consumption While Breastfeeding

Findings from recently published studies, including the LEAP study, have led to rapid acceptance of the introduction of peanuts during the first year of life. “This new philosophy is reflected in revised guidelines from national pediatric and allergy societies,” says Meghan Azad, PhD. “However, these recent studies and new guidelines do not address the role of breastfeeding and maternal ingestion of peanut.” For a study published in the Journal of Allergy and Clinical Immunology, Dr. Azad, Tracy Pitt, MD, FRCPC, and colleagues performed a secondary analysis of data from a previous allergy and asthma study that tracked children born in 1995 from birth to age 15. “All infants in the study had an immediate family history of asthma or two relatives with immunoglobulin E-mediated allergic disease. Mothers were randomized during pregnancy to standard care (control) or a multifaceted intervention that included maternal peanut avoidance and delayed introduction of peanut and other allergenic foods. Infants were assessed at multiple time points throughout early childhood and tested for peanut sensitization at age 7.” The researchers found, in this high-risk group of breast-fed children, an association between early peanut introduction in the first year of life and reduced risk of peanut sensitization by age 7. “But the association only occurred if mothers also consumed peanuts while breastfeeding,” stresses Dr. Azad. “Both exposures were necessary for this protective effect to occur.” The study suggests that encouraging peanut consumption while breastfeeding in combination with early direct peanut exposure may decrease the risk of peanut sensitization in high-risk children, according to Dr. Pitt. However, “further research is needed to determine if the current findings for peanut...
Differential Immunodominance Hierarchy of CD8T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection.

Differential Immunodominance Hierarchy of CD8T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection.

Journal of virology 2018 01 3092(4) pii 10.1128/JVI.01685-17 Abstract The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8T-cell responses that dominate HIV-specific CD8T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.CD8T cells play...
Control of Human T-Cell Leukemia Virus Type 1 (HTLV-1) Infection by Eliminating Envelope Protein-Positive Cells with Recombinant Vesicular Stomatitis Viruses Encoding HTLV-1 Primary Receptor.

Control of Human T-Cell Leukemia Virus Type 1 (HTLV-1) Infection by Eliminating Envelope Protein-Positive Cells with Recombinant Vesicular Stomatitis Viruses Encoding HTLV-1 Primary Receptor.

Journal of virology 2018 01 3092(4) pii 10.1128/JVI.01885-17 Abstract Human T-cell leukemia virus type 1 (HTLV-1) infection causes adult T-cell leukemia (ATL), which is frequently resistant to currently available therapies and has a very poor prognosis. To prevent the development of ATL among carriers, it is important to control HTLV-1-infected cells in infected individuals. Therefore, the establishment of novel therapies with drugs specifically targeting infected cells is urgently required. This study aimed to develop a potential therapy by generating recombinant vesicular stomatitis viruses (rVSVs) that lack an envelope glycoprotein G and instead encode an HTLV-1 receptor with human glucose transporter 1 (GLUT1), neuropilin 1 (NRP1), or heparan sulfate proteoglycans (HSPGs), including syndecan 1 (SDC1), designated VSVΔG-GL, VSVΔG-NP, or VSVΔG-SD, respectively. In an attempt to enhance the infectivity of rVSV against HTLV-1-infected cells, we also constructed rVSVs with a combination of two or three receptor genes, designated VSVΔG-GLN and VSVΔG-GLNS, respectively. The present study demonstrates VSVΔG-GL, VSVΔG-NP, VSVΔG-GLN, and VSVΔG-GLNS have tropism for HTLV-1 envelope (Env)-expressing cells. Notably, the inoculation of VSVΔG-GL or VSVΔG-NP significantly eliminated HTLV-1-infected cells under the culture conditions. Furthermore, in an HTLV-1-infected humanized mouse model, VSVΔG-NP was capable of efficiently preventing HTLV-1-induced leukocytosis in the periphery and eliminating HTLV-1-infected Env-expressing cells in the lymphoid tissues. In summary, an rVSV engineered to express HTLV-1 primary receptor, especially human NRP1, may represent a drug candidate that has potential for the development of unique virotherapy against HTLV-1infection.Although several anti-ATL therapies are currently available, ATL is still frequently resistant to therapeutic approaches, and its prognosis remains poor. Control of HTLV-1infection or expansion of HTLV-1-infected cells in the carrier holds considerable...
Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

Journal of virology 2018 02 1292(5) pii 10.1128/JVI.01883-17 Abstract Recently discovered broadly neutralizing antibodies (bNAbs) against HIV-1 demonstrate extensive breadth and potency against diverse HIV-1 strains and represent a promising approach for the treatment and prevention of HIV-1 infection. The breadth and potency of these antibodies have primarily been evaluated by using panels of HIV-1 Env-pseudotyped viruses produced in 293T cells expressing molecularly cloned Env proteins. Here we report on the ability of five bNAbs currently in clinical development to neutralize circulating primary HIV-1 isolates derived from peripheral blood mononuclear cells (PBMCs) and compare the results to those obtained with the pseudovirus panels used to characterize the bNAbs. The five bNAbs demonstrated significantly less breadth and potency against clinical isolates produced in PBMCs than against Env-pseudotyped viruses. The magnitude of this difference in neutralizing activity varied, depending on the antibody epitope. Glycan-targeting antibodies showed differences of only 3- to 4-fold, while antibody 10E8, which targets the membrane-proximal external region, showed a nearly 100-fold decrease in activity between published Env-pseudotyped virus panels and PBMC-derived primary isolates. Utilizing clonal PBMC-derived primary isolates and molecular clones, we determined that the observed discrepancy in bNAb performance is due to the increased sensitivity to neutralization exhibited by 293T-produced Env-pseudotyped viruses. We also found that while full-length molecularly cloned viruses produced in 293T cells exhibit greater sensitivity to neutralization than PBMC-derived viruses do, Env-pseudotyped viruses produced in 293T cells generally exhibit even greater sensitivity to neutralization. As the clinical development of bNAbs progresses, it will be critical to determine the relevance of each of theseneutralization assays toantibody performance.Novel therapeutic and preventive strategies are needed to...
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