Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants

BackgroundPapua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world.MethodsNasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray.ResultsPneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log₁₀ genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes.ConclusionPNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered.     

Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness

BackgroundIndigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults.MethodsSerotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3 μg/ml but <4.0 μg/ml; or a post-vaccination antibody concentration >4.0 μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N = 20) and Indigenous (N = 60) and non-Indigenous adults (N = 25) receiving their first 23vPPV dose.ResultsAll non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p = 0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (−27%, 95% CI: −43% to −11%; p = 0.01) and 90% (−38%, 95% CI: −60% to −16%; p = 0.006) of serotypes with a positive response.ConclusionIndigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.     

山茱萸多糖对衰老大鼠晶状体中Sirt1基因表达的影响

目的：初步探讨山茱萸多糖治疗年龄相关性白内障的可能机制，为其预防和治疗寻找新的药物和靶点。方法：选用60只昆明大鼠，按体质量随机分为3组，每组20只，分别为对照组（C组）、衰老模型组（A组）和山茱萸多糖给药组（D组）。在相同环境下，C组正常饮食，每日颈背部皮下注射0．9％氯化钠注射液，剂量计算参照其他给药组D-半乳糖给药量；A和D组正常饮食，每日颈背部皮下注射D-半乳糖100mg／（kg·d）；连续皮下注射45d后，C和A组每日按照等剂量灌药量灌服温开水；D组按照多糖0．4g／蛞灌服山莱萸多糖，连续灌服30d。试验终期颈椎离断术处死大鼠，4℃迅速取眼分离晶状体置于液氮备用。免疫组化方法检测各组间总超氧化物歧化酶（T-SOD）和总抗氧化能力（T-AOC）的变化，RT—PCR（逆转录cDNA的聚合酶链式扩增反应）检测各组Sirt1、p53和FOXO1 mRNA的表达变化。结果：A组和D组大鼠晶状体中Sirt1 mRNA的表达较C组均显著上升（P〈0．05、P〈0．01），且D组较A组显著上升（P〈0．01）；A组和D组大鼠晶状体中p53 mRNA的表达较C组显著上升（P均〈0．01），而D组较A组显著下降（P〈0．05）；A组和D组大鼠晶状体中FOXO1 mRNA的表达较C组显著上升（P〈0．05、P〈0．01），且D组较A组显著上升（P〈0．01）。另外A组和D组大鼠晶状体中T—SOD的活性较C组显著上升（P均〈0．01），且D组较A组显著上升（P〈0．01）；A纽和D组大晶状体中鼠T-AOC的活性较C组显著上升（P均〈0．01），且D较A组显著上升（P〈0．01）。结论：山茱萸多糖可能通过调节Sirt1的表达，从而调节下游基因p53和FOXO1的表达，最终抑制或延缓晶状体上皮细胞的凋亡，减缓年龄相关性白内障的进展。     

枸杞多糖对颅内动脉瘤大鼠NF-κB信号通路及血管内皮组织炎性损伤的影响

目的 探讨枸杞多糖(LBP)对颅内动脉瘤(IA)大鼠核蛋白因子-κB(NF-κB)蛋白通路及血管内皮组织炎性损伤的影响。方法 取SD雌性大鼠50只,采用切除双侧卵巢并结扎左侧颈总动脉及双侧肾动脉后支以构建IA模型,随机分为IA模型组、LBP低(5 mg/kg)、中(10 mg/kg)、高(20 mg/kg)剂量组,另取10只大鼠,只暴露卵巢、颈总动脉、双侧肾动脉后支,不进行摘除和结扎,作为对照组(Control组); 各组均于手术1周后,开始给药,Control组、IA模型组经灌胃给予生理盐水,LBP各剂量组灌胃给予相应剂量药物,1次/d,共给药30 d; 末次给药12 h后处死,取大鼠血液用酶联免疫吸附法(ELISA)检测血清炎性因子白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)及血管内皮损伤标志物血管内皮生长因子(VEGF)、血管内皮素(ET)水平; 分离取出大鼠脑动脉(Wills)环,在40倍显微镜下检查大脑动脉(Wills)环病理改变,并检测动脉瘤血管壁厚度及动脉瘤体积; 取脑动脉瘤血管组织,用苏木精-伊红染色(HE)检测动脉瘤血管组织病理变化; 蛋白免疫印迹法(Western blot)检测动脉瘤血管组织NF-κB,Toll样受体-4(TLR4)蛋白表达水平。结果 与Control组比较,IA模型组大鼠Willis环上凸起、管壁厚度和肿动脉瘤体积、动脉瘤内皮细胞空泡变性及炎性细胞浸润等病理损伤程度、血清IL-6,TNF-α,VEGF,ET水平、动脉瘤血管组织NF-κB和TLR4蛋白表达水平明显升高(P<0.05); 与IA模型组比较,LBP低、中、高剂量组大鼠Willis环上凸起、管壁厚度和动脉瘤体积、动脉瘤内皮细胞空泡变性及炎性细胞浸润等病理损伤程度、血清IL-6,TNF-α,VEGF,ET水平、动脉瘤血管组织NF-κB和TLR4蛋白表达水平明显降低(P<0.05),且LBP各剂量组上述指标水平呈剂量依赖性降低。结论 LBP可能通过抑制TLR4/NF-κB通路激活、降低炎症反应来减轻IA血管内皮组织损伤。     

A Study on the Extraction and Purification Process of Lily Polysaccharide and Its Anti-Tumor Effect

The objective of this paper was to extract and purify lily polysaccharide and to study its anti-H22 hepatoma effect in mice. Orthogonal experimental method was used to analyze the factors influencing the extraction and purification of lily polysaccharide, and the anti-tumor effect of lily polysaccharide was studied by acting it on H22-bearing mice. The results showed that the size of influence of various factors on the extraction results of lily polysaccharide were extraction time, extraction times and extraction temperature in decreasing order. Lily polysaccharide can enhance the immune function of H22 tumor-bearing mice, and inhibit the growth of H22 tumor. The study concluded that the optimal conditions for the extraction and purification of lily polysaccharide should be extraction times of 3 times, an extraction time of 4 h each, and an extraction temperature of 60°C; lily polysaccharide has an anti-tumor effect.     

Short Communication Effect of sulfated polysaccharides on hepatocyte adhesion

The effects of sulfated polysaccharides on hepatocyte adhesion on the polystyrene dish and fibronectin-coated dish were investigated. Dextran sulfate and synthetic mannopyranan sulfate slightly inhibited hepatocyte adhesion on fibronectin-coated dish, while heparin showed no effect. On the other hand, hepatocyte adhesion on polystyrene dishes was stimulated in the presence of sulfated polysaccharides in the medium.     

A new tool to test active ingredient using lactic acid in vitro,a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel®)

The stinging test is an in vivo protocol that evaluates sensitive skin using lactic acid (LA). A soothing sensation of cosmetics or ingredients can be also appreciated through a decrease in stinging score. To predict the soothing sensation of a product before in vivo testing, we developed a model based on an LA test and substance P (SP) release using a co‐culture of human keratinocytes and NGF‐differentiated PC12 cells. A bacterial fucose‐rich polysaccharide present in Fucogel^® was evaluated as the soothing molecule in the in vivo stinging test and our in vitro model. Excluding toxic concentrations, the release of SP was significant from 0.2% of lactic acid for the PC12 cells and from 0.1% of lactic acid for the keratinocytes. When the pH was adjusted to approximately 7.4, LA did not provoke SP release. At these concentrations of LA, 0.1% of polysaccharide showed a significant decrease in SP release from the two cellular types and in co‐cultures without modifying the pH of the medium. In vivo, a stinging test using the polysaccharide showed a 30% decrease in prickling intensity vs the placebo in 19 women between the ages of 21 and 69. Our in vitro model is ethically interesting and is adapted for cosmetic ingredients screening because it does not use animal experimentation and limits human volunteers. Moreover, Fucogel^® reduced prickling sensation as revealed by the in vivo stinging test and inhibits the neurogenic inflammation as showed by our new in vitro stinging test based on SP release.     

Translating vaccine policy into action: A report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings

Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life.