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: Type 1 diabetes mellitus (T1DM) is an autoimmune disease which leads to destruction of pancreatic β-cells, thereby causing insufficient insulin production. Globally, around 98, 200 children and adolescents below 15 years of age and almost 128,900 subjects below 20 years of age develop T1DM annually, along with severe complications deteriorating their quality of life. In India alone, around 15,900 incident cases below 15 years have reported annually. Hence, its prevention and reversal are significant. Unlike other chronic diseases, T1DM involves the presence of various autoantigens which can be targeted by proper immunisation. The development of reliable immuno-regulatory surrogate markers would be of a great benefit. Vaccines can be one of such strategies in the journey to prevent T1DM. It would not only benefit greatly to reduce the sufferings caused due to diabetic complications but could also help to reverse T1DM, by modulating the immunological autoantigenic reactions and prevent further degradation of pancreatic β-cells. This review collates a wide range of information related to the vaccine studies conducted in animal and human models to prevent and reverse T1DM.

This first in human study was designed as an open label clinical trial to assess the safety and immunogenicity of SIIPL DTwP-HepB-IPV-Hib (Hexavalent) combination vaccine in healthy toddlers, aged 16–24 months. A total of 24 healthy toddlers were administered a 0.5 ml single dose of SIIPL DTwP-HepB-IPV-Hib vaccine intramuscularly, and followed for 28 days for safety outcomes viz. immediate, solicited, unsolicited and serious adverse events. Blood samples were collected immediately prior to and 28 days after vaccination to assess the immunogenicity. Twenty four completed the study in compliance with the study protocol. None of the participants experienced any immediate or any serious adverse event. In terms of the frequency and intensity, the adverse events were comparable to DTwP-based combination vaccines. The vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. One month post booster vaccination seroprotection for diphtheria, tetanus, Hepatitis B, Haemophilus influenzae type b and polio virus type 1 and 3 was 100%. The percentage sero-response for pertussis was 75%. Four-fold increase in antibody concentration for pertussis was achieved in 87.5% subjects. Indigenously developed DTwP-HepB-IPV-Hib vaccine by Serum Institute of India Pvt. Ltd. was found to be safe, well tolerated and showed a robust immune response in toddlers. It was concluded that this vaccine should be assessed in the next phases of clinical development in the target population. Clinical Trial Registration – CTRI/2018/10/015875.

<em>Sansevieria cylindrica</em> (SC) Bojer ex Hook. (Asparagaceae) and <em>Plumeria obtusa</em> (PO) L. (Apocynaceae) are indoor and outdoor ornamental plants respectively. These plants are traditionally used by the local healers during accidental injuries. However, their toxicological properties are very poorly explored over folkloric usage. Therefore, the present study evaluated the toxic potencies of SC leaves and PO seed Hydro-Alcoholic Extract (SCPOHAE) through acute oral dose (14-days) administration in female Wistar rats. Safety of the SCPOHAE was evaluated as per Organization for Economic Co-operation and Development (OECD) Acute Oral Toxicity study guidelines 423. The female Wistar rats were divided into three groups (n=3). A single oral dose of 2000 mg/kg of body weight of individual extract and 1:1 blend was administered to each animal. The animals were closely observed for clinical signs, neurobehavioral changes, morbidity, and mortality if any for the first half an hour and then every hour for the first four hours followed by observation every 24–hours for 14 days. Changes in food and water consumption, body weight were monitored daily during the study. On day 1 and day 15 blood samples were collected to evaluate changes in the hematology and biochemistry parameters. The urine samples were also collected for urine analysis parameters. Animals were sacrificed on day 15 and organ samples of liver and kidney were collected for histopathological findings. The SCPOHAE individually and also as 1:1 blend at the limit dose (2000 mg/kg, body weight) did not cause death and did not induce any remarkable and abnormal clinical signs, indicative of systemic toxicity, in rats during the treatment period of 14–days. The statistically non-significant small differences in the body weight were observed. <strong>Conclusion:</strong> The oral administration of SCPOHAE did not cause any systemic toxic effects. In conclusion, the No-observed-Adverse-Effect Level (NOAEL) of these extracts in rats was found to be greater than 2000 mg/kg.

BackgroundLuminex bead-based assays offer multiplexing to test antibodies against multiple antigens simultaneously; however, this requires validation using internationally certified reference standards. Therefore, there is an urgent need to characterize existing reference standards for the standardization of multiplex immunoassays (MIAs). Here, we report the development and validation of an MIA for the simultaneous estimation of levels of human serum immunoglobulin G (IgG) antibodies for pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT).MethodsThe MIA was assessed using a panel of human serum samples and WHO reference standards. The WHO reference standards were also studied for suitability in the MIA. Purified antigens (PT, FHA, PRN, DT, and TT) were coupled to the spectrally unique magnetic carboxylated microspheres. The method was validated in accordance with the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and the International Committee of Harmonization Multidisciplinary (ICH M10) guidelines, and parameters such as precision, accuracy, dilutional linearity, assay range, robustness, and stability were assessed. Method agreements with commercially available IgG enzyme-linked immunosorbent assay (ELISA) assays were also evaluated. In addition, the study assessed the level of correlation between the IgG levels estimated by the MIA and the cell-based neutralizing antibody assays for PT and DT.ResultsWe identified that an equimix of WHO international standards (i.e., 06/142, 10/262, and TE-3) afforded the best dynamic range for all the antigens in the MIA. For all five antigens, we observed that the back-fitted recoveries using the four-parameter logistic (4-PL) regression fits ranged between 80% and 120% for all calibration levels, and the percentage coefficient of variation (% CV) was &lt; 20%. In addition, the difference in mean fluorescence intensity (MFI) between the monoplex and multiplex format was &lt; 10% for each antigen, indicating no crosstalk among the beads. The MIA also showed good agreement with conventional and commercially available assays, and a positive correlation (&gt; 0.75) with toxin neutralization assays for PT and DT was observed.ConclusionThe MIA that was calibrated in accordance with WHO reference standards demonstrated increased sensitivity, reproducibility, and high throughput capabilities, allowing for the design of robust studies that evaluate both natural and vaccine-induced immunity.