A novel high throughput plate-based method for 2-PE quantification in novel multidose vaccines (R21 malaria,Covishield and Covovax) and combination vaccines (Hexavalent)

Multidose presentation of vaccines is the most preferred choice, for mass immunization particularly during pandemics. WHO also recommends multidose containers of fill finished vaccines for programmatic suitability and global immunizations programmes. However, multidose vaccine presentations requires inclusion of preservatives to prevent contaminations. 2-Phenoxy ethanol (2-PE) is one such preservative which is being used in numerous cosmetics and many vaccines recently. Estimation of 2-PE content in multidose vials is a crucial quality control parameter to ensure in use stability of the vaccines. Presently available conventional methods, have their own limitation in terms of being time consuming, requiring sample extraction, large sample volume requirement etc. Therefore, a robust, simple, high-throughput method with a low turnaround time was required, which can quantitate 2-PE content in the conventional combination vaccines as well as new generation complex VLP based vaccines. In order to address this issue, a novel absorbance-based method has been developed. This novel method specifically detects 2-PE content in Matrix M1 adjuvanted R21 malaria vaccine, nano particle and viral vector based covid vaccines and combination vaccines like Hexavalent vaccine. The method has been validated for parameters such as linearity, accuracy and precision. Importantly, this method works even in presence of high amounts of proteins and residual DNA. Considering the advantages associated with method under study, this method can be used as an important in process or release quality parameter to estimate the 2-PE content in various vaccines containing 2-PE in multidose presentations.     

Adiposity,hepatic steatosis,and metabolic health transitions in people with obesity: Influences of age and sex

Background and aimsMetabolically healthy (MHO) and unhealthy obesity (MUO) may be transient conditions. This study aimed to quantify and identify predictive factors of metabolic transitions in obesity, exploring influences of age and sex.Methods and resultsWe retrospectively evaluated adults with obesity who underwent routine health evaluation. In a cross-sectional analysis of 12,118 individuals (80% male, age 44.3 ± 9.9 years), 16.8% had MHO. In a longitudinal evaluation of 4483 participants, 45.2% of individuals with MHO at baseline had dysmetabolism after a median follow-up of 3.0 (IQR 1.8–5.2) years, whereas 13.3% MUO participants became metabolically healthy (MH). Development of hepatic steatosis (HS, ultrasound) was an independent predictor of MHO conversion to dysmetabolism (OR 2.36; 95% CI 1.43, 3.91; p < 0.001), while HS persistence was inversely associated with transition from MUO to MH status (OR 0.63; 95% CI 0.47, 0.83; p = 0.001). Female sex and older age were associated with a lower chance of MUO regression. A 5% increment in body mass index (BMI) over time increased the likelihood of metabolic deterioration by 33% (p = 0.002) in females and 16% (p = 0.018) in males with MHO. A 5% reduction in BMI was associated with a 39% and 66% higher chance of MUO resolution in females and males, respectively (both p < 0.001).ConclusionThe findings support a pathophysiological role of ectopic fat depots in metabolic transitions in obesity and identify female sex as an aggravating factor for adiposity-induced dysmetabolism, which has implications for personalized medicine.     

The association between meat intake and the risk of coronary heart disease in Korean men using the Framingham risk score: A prospective cohort study

Background and aimsResearch suggests that meat intake may increase the risk of coronary heart disease (CHD), but most studies take place in Western countries, where the types and amount of meat products consumed differ from those in Asian countries. We aimed to identify the association between meat intake and CHD risk in Korean male adults, using the Framingham risk score.Methods and resultsWe used data from the Korean Genome and Epidemiology Study (KoGES) Health Examinees (HEXA) study, including 13,293 Korean male adults. We estimated the association of meat intake with ≥20% 10-year CHD risk using Cox proportional hazards regression models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects with the highest total meat intake had a 53% (model 4: HR 1.53, 95% CI 1.05–2.21) increased 10-year CHD risk compared to those with the lowest intake. Those with the highest red meat intake had a 55% (model 3: HR 1.55, 95% CI 1.16–2.06) increased 10-year CHD risk compared to those with the lowest intake. No association was observed between poultry or processed meat intake and 10-year CHD risk.ConclusionsConsumption of total meat and red meat was associated with a higher risk of CHD in Korean male adults. Further studies are needed to provide criteria for the appropriate meat intake by meat type to reduce CHD risk.     

Challenges and opportunities in developing a Shigella-containing combination vaccine for children in low- and middle-income countries: Report of an expert convening

The gram-negative bacterium Shigella is an enteric pathogen responsible for significant morbidity and mortality due primarily to severe diarrhea and dysentery, mainly among children younger than five years of age living in low- and middle-income countries (LMICs). Long considered a priority target for vaccine development, recent scientific advances have led to a number of promising Shigella vaccine candidates now entering advanced stages of clinical testing. Yet, there is no guarantee that even a highly efficacious Shigella vaccine will be recommended, prioritized, purchased, and widely adopted—especially if it requires additional doses in the immunization schedule and/or visits within the immunization program. This uncertainty is due to a variety of factors, including continuing declines in Shigella-specific and overall diarrheal disease mortality rates, the increasing complexity and cost of infant immunization programs in LMICs, and the recent availability of other high-priority vaccines. Since combining a Shigella vaccine with an existing infant vaccine would conceivably increase its attractiveness, there is a need to systematically consider the challenges determining the public health value, clinical development, manufacturing, licensure, policy recommendations, and financing for a Shigella-containing combination vaccine.The international non-governmental health organization PATH convened an independent panel of 34 subject matter experts across academic, industry, philanthropic, and global health sectors to discuss hypothetical combinations of a notional parenteral Shigella vaccine with three existing vaccines in order to begin exploring the challenges associated with their development. The resulting insights and recommendations from this meeting contribute to PATH’s broader effort to evaluate the public health value of potential Shigella vaccines. They may also help guide future combination vaccine development efforts more broadly.     

Maternity care provider acceptance of a future Group B Streptococcus vaccine – A qualitative study in three countries

IntroductionThere are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). When approved, GBS vaccines will be intended for administration to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its’ uptake in the population. Experience with prior maternal vaccines, e.g. influenza, Tdap and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women, and that provider recommendation is a key driver of vaccine uptake.MethodsThis study investigated attitudes of maternity care providers towards the introduction of a GBS vaccine in three countries (the United States (US), Ireland, and the Dominican Republic (DR)) with different GBS prevalence and prevention practices. Semi-structured interviews with maternity care providers were transcribed and coded for themes. The constant comparative method, and inductive theory building were used to develop conclusions.ResultsThirty-eight obstetricians, 18 general practitioners and 14 midwives participated. There was variability in provider attitudes towards a hypothetical GBS vaccine. Responses ranged from enthusiasm to doubts over the need for a vaccine. Attitudes were influenced by perceived additional benefits of a vaccine over current strategy and confidence in the safety of vaccines during pregnancy. Knowledge, experience and approaches to GBS prevention differed geographically and according to provider type, and influenced how participants assessed the risks and benefits of a GBS vaccine.ConclusionMaternity care providers are engaged in the topic of GBS management and there is opportunity to leverage attitudes and beliefs that will support a strong recommendation for a GBS vaccine. However, knowledge of GBS, and of the limitations of current prevention strategies vary among providers in different regions, and between different provider types. Targeted educational efforts with antenatal providers should focus on highlighting safety data the potential benefits of vaccination over current strategies.     

Safety and immunogenicity of Multimeric-001 (M-001) followed by seasonal quadrivalent inactivated influenza vaccine in young adults – A randomized clinical trial

BackgroundThe continuing evolution of influenza viruses poses a challenge to vaccine prevention, highlighting the need for a universal influenza vaccine. We evaluated the safety and immunogenicity of one such candidate, Multimeric-001 (M-001), when used as a priming vaccine prior to administration of quadrivalent inactivated influenza vaccine (IIV4).MethodsHealthy adults 18 to 49 years of age were enrolled in a phase 2 randomized, double-blind placebo-controlled trial. Participants received two doses of either 1.0-mg M-001 or saline placebo (60 per study arm) on Days 1 and 22 followed by a single dose of IIV4 on about Day 172. Safety, reactogenicity, cellular immune responses and influenza hemagglutination inhibition (HAI) and microneutralization (MN) were assessed.ResultsThe M-001 vaccine was safe and had an acceptable reactogenicity profile. Injection site tenderness (39% post-dose 1, 29% post-dose 2) was the most common reaction after M-001 administration. Polyfunctional CD4+ T cell responses (perforin-negative, CD107α-negative, TNF-α+, IFN-γ+, with or without IL-2) to the pool of M-001 peptides increased significantly from baseline to two weeks after the second dose of M-001, and this increase persisted through Day 172. However, there was no enhancement of HAI or MN antibody responses among M-001 recipients following IIV4 administration.ConclusionsM-001 administration induced a subset of polyfunctional CD4+ T cells that persisted through 6 months of follow-up, but it did not improve HAI or MN antibody responses to IIV4. (clinicaltrials.gov NCT03058692).     

Combined effects of high sensitivity C-reactive protein and triglyceride–glucose index on risk of cardiovascular disease among middle-aged and older Chinese: Evidence from the China Health and Retirement Longitudinal Study

Background and aimsHigh sensitivity C-reactive protein (hsCRP) and triglyceride glucose (TyG) index were proved to be independent risk factors of cardiovascular disease (CVD). However, individual hsCRP or TyG index might not provide sufficient predictive value on CVD risk. The current study aimed to evaluate the cumulative effect of hsCRP and TyG index on CVD risk prospectively.Methods and resultsA total of 9626 participants were enrolled in the analysis. The TyG index was calculated as ln(triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The primary outcome was new-onset CVD events (cardiac events or stroke), and the secondary outcomes were new-onset cardiac events and stroke, separately. Participants were divided into 4 groups through the median of hsCRP and TyG index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportion hazard models. From 2013 to 2018, 1730 participants experienced CVD (570 stroke and 1306 cardiac events). Linear associations were found between hsCRP, TyG index, hsCRP/TyG ratio and CVD (all p < 0.05). Compared to participants with low hsCRP/low TyG index, multivariable adjusted HRs (95% CIs) for those with high hsCRP/high TyG index were 1.17 (1.03–1.37) for CVD. No interaction of hsCRP and TyG index was found on CVD (p_-interaction ≥0.05). Furthermore, adding hsCRP and TyG index simultaneously to conventional risk model improved risk reclassification for CVD, stroke and cardiac events (all p < 0.05).ConclusionThe present study suggested combination of hsCRP and TyG index might better improved the ability for risk stratification of CVD among middle-aged and older Chinese.     

Parental disability and children's educational,labor market and marital outcomes: Evidence from Nepal

BackgroundThe extent to which parental disability affects children's educational, employment, and marital outcomes in low-income countries is poorly understood, limiting the countries' efforts to design and implement disability-inclusive policies.ObjectiveTo assess the association between parental disability and children's education, employment, and marital outcomes in Nepal, and variations in these associations by sex.MethodUsing a nationally representative 15% sample of the 2011 census, we examine the relationship between parental disability and children's outcomes in a regression framework, controlling for potential confounders. We also test if the associations vary by the individual's sex.ResultsFather's disability is not associated with any of the outcomes for boys except enrolment status. However, for girls, it is associated also with lower chances of being at the appropriate grade and higher chances of being employed. Mother's disability is associated with lower chances of being at the appropriate grade, lower educational attainment, higher chances of being employed, and earlier marriage for boys. For girls, it is associated only with lower chances of being at the appropriate grade and being employed.ConclusionsAdverse effects of parental disability can last across generations in a low-income setting and can vary by the individual's sex. Further research is needed to ascertain causal pathways and intervening mechanisms.