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To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9–14 years cohort. This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9–14 years or 15–26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9–14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15–26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9–14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15–26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry – India (CTRI/2018/06/014601), and long-term follow-up is ongoing. Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9–14 years and 1200 (819 women and 381 men) in the cohort aged 15–26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215–231) for girls and 222 days (217–230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216–232) for girls in the comparator vaccine group, and 222 days (216–230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67–2·32) for HPV type 6, 1·63 (1·38–1·91) for HPV type 11, 1·90 (1·60–2·25) for HPV type 16, and 2·16 (1·79–2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57–2·21) for HPV type 6, 1·46 (1·23–1·73) for HPV type 11, 1·62 (1·36–1·94) for HPV type 16, and 1·80 (1·48–2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3–4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9–14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.

The rising incidence of neurodegenerative diseases represents a significant global health concern. The prognosis for such diseases is often unfavorable, and patients require supportive treatment to manage their condition effectively. The present study investigated the anti-oxidative, anti-acetylcholinesterase (anti-AChE) effect of hydro-alcoholic extract of Sansevieria cylindrica leaves and Plumeria obtusa seed pods in Wistar rats. Plants were authenticated followed by pharmacognostic evaluation. The antioxidant and anti-AChE activities were evaluated by scopolamine-induced oxidative stress and acetylcholine level alterations in Wistar rats. On the 0th, 7th, and 14th days during study period behavioral parameters were evaluated, including open field test, new object recognition test, and Morris water maze task. Different antioxidant enzymes were also evaluated in brain homogenate post 7 days treatment. AChE levels in rats’ brains were assessed post 14 days of treatment. Finally, histopathology of brains samples was performed. Correspondingly, in-vitro and in-silico studies were done to support the study findings. Results Sansevieria cylindrica and Plumeria obtusa exhibited strong antioxidant and anti-AChE activities due to secondary metabolites content. Rearing and, line crossing by rats showed substantial alteration ( p  < 0.05) by combination of both plants at high dose. The escape latency found to be reduced significantly ( p  < 0.05) by Sansevieria cylindrica individually and in combination with Plumeria obtusa at all doses. The lipid peroxidation level in brain was decreased significantly than standard at 1:1 combination of plants extracts. The levels of GSH, CAT and SOD were attenuated significantly by different concentration of extracts ( p  < 0.05 and p  < 0.001, respectively). The reduction in AChE levels was around 34.62% and 31.10% in male and female rats, respectively in combination of both plants at high dose compared to disease control group. It was further evident in brain histopathology. All in-vivo results were supported by in-vitro free radicals scavenging effect and in-silico study. Conclusion The hydro-alcoholic extracts from Plumeria obtusa seed pods and Sansevieria cylindrica leaves showed a strong natural antioxidant, and acetylcholinesterase inhibitions which can aid in the treatment of neurodegerative diseases including Alzheimer.

Spindle cell sarcomas of the right atrium are extremely rare primary cardiac tumours with very few cases reported in the medical literature. The prognosis of this malignant neoplasm remains poor due to delay in diagnosis, early metastasis and few available therapeutic options. It responds poorly to chemotherapy and radiotherapy. Surgical excision is the mainstay of treatment. We report a 42-year-old man, who presented to emergency room with dyspnoea and fatigue (New York Heart Association classification II) since 1 month. Transthoracic echocardiogram showed massive pericardial effusion with tamponade. The patient underwent emergency pericardiocentesis; postpericardiocentesis echocardiogram showed large right atrial mass involving the right ventricle and the tricuspid valve causing tricuspid stenosis. Findings were confirmed by cardiac CT scan. Percutaneous transvenous biopsy was carried out which revealed spindle cell sarcoma.

► Hib vaccine manufactured in small or large scale were equally immunogenic and safe. ► Both vaccines provided adequate seroprotection in the target population. ► Neither immunological interference nor increased reactogenicity was observed. ► Scaled up vaccine can be easily incorporated in the routine immunization programme. Hib vaccine can be easily incorporated in EPI vaccination schedule as the immunization schedule of Hib is similar to that of DTP vaccine. To meet the global demand of Hib vaccine, SIIL scaled up the Hib conjugate manufacturing process. This study was conducted in Indian infants to assess and compare the immunogenicity and safety of DTwP-HB+Hib (Pentavac®) vaccine of SIIL manufactured at large scale with the ‘same vaccine’ manufactured at a smaller scale. 720 infants aged 6–8 weeks were randomized (2:1 ratio) to receive 0.5ml of Pentavac® vaccine from two different lots one produced at scaled up process and the other at a small scale process. Serum samples obtained before and at one month after the 3rd dose of vaccine from both the groups were tested for IgG antibody response by ELISA and compared to assess non-inferiority. Neither immunological interference nor increased reactogenicity was observed in either of the vaccine groups. All infants developed protective antibody titres to diphtheria, tetanus and Hib disease. For hepatitis B antigen, one child from each group remained sero-negative. The response to pertussis was 88% in large scale group vis-à-vis 87% in small scale group. Non-inferiority was concluded for all five components of the vaccine. No serious adverse event was reported in the study. The scale up vaccine achieved comparable response in terms of the safety and immunogenicity to small scale vaccine and therefore can be easily incorporated in the routine childhood vaccination programme.

Introduction: Serologic surveys conducted in different countries indicate that rubella is a worldwide infection. Several such sero surveys conducted in India have also confirmed that 6-47% of women are susceptible to rubella infection. The current study was conducted on 1,329 female adolescents in 12 districts of Maharashtra, India, to assess their serological status in terms of rubella exposure. Methodology: After enrollment, a pre-vaccination blood sample was collected from the participants followed by rubella vaccination (R-vac). Adverse events were monitored for the next 6-8 weeks, at which time a post-vaccination sample was collected. Results: Pre-vaccination rubella immunity was higher in the urban (80.2%) population compared to the rural (73.1%) population. Following R-vac vaccination, out of 1,159 participants who completed the study, all (100%) in the urban and 99.5% of participants in the rural area developed antibodies against rubella. Conclusion: Substantial numbers of women reach childbearing age without immunity against rubella and thus are at a risk of passing the infection to their fetuses, who can then develop subsequent congenital defects leading to congenital rubella syndrome (CRS). An immunization policy recommending vaccination with rubella or rubella containing vaccine is highly desirable to prevent rubella and CRS. 

•To avoid a global pertussis resurgence, booster Tdap immunization is recommended.•Global shortages of acellular pertussis vaccines have been reported.•Safety and immunogenicity of SIIPL Tdap was compared to an approved Tdap vaccine.•SIIPL Tdap immune responses were non-inferior to comparator Tdap vaccine.•SIIPL Tdap was safe and well tolerated. This study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap). The Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4–65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of −10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components. At Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported. Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated. EudraCT number: 2019-002706-46.

Combination vaccines are effective in simplifying complex vaccination schedules involving multiple vaccines. A fully liquid hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)- hepatitis B (HepB)-inactivated poliovirus (IPV)-Haemophilus influenzae b (Hib) vaccine (HEXASIIL®), manufactured by Serum Institute of India Pvt. Ltd. was tested for safety and immunogenicity following booster vaccination. This was a phase-II/III, open label, multicentric, controlled trial in toddlers (phase II) and infants (phase III) in India. This manuscript presents results of phase II. Healthy toddlers aged 12–24 months were randomized (1:1) to receive a 0.5 ml booster dose of HEXASIIL® or comparator Pentavac SD + Poliovac, intramuscularly and followed for 28 days for safety assessment. Blood samples were collected pre-vaccination and 28 days post-vaccination to assess immunogenicity. Descriptive summary statistics were provided for safety and immunogenecity analyses. A total of 223 subjects were randomized. One subject droped out prior to dosing, due to consent withdrawal. Thus, 222 subjects received study vaccine (110 HEXASIIL® and 112 comparator). Frequency of solicited adverse events was comparable between HEXASIIL® and comparator (85.5 % vs 90.2 %). Most local and systemic solicited AEs were mild to moderate in severity. All events resolved completely without any sequelae and none led to subject discontinuation. No vaccine related serious AE was reported. Post vaccination, seroprotection rates against tetanus, Hib and polio type 1 and 3 were 100 % in both the groups. Seroprotection rates for diphtheria (99.1 % vs 100 %) and polio type 2 (98.2 % vs 100 %) were observed in HEXASIIL® and comparator group, respectively. For Hepatitis B, seroprotection was >99 % in both groups. Seroconversion observed for Bordetella Pertussis (94.5 % vs 95.4 %) and Pertussis Toxin (77.1 % vs 87.2 %) in HEXASIIL® and comparator group, respectively. HEXASIIL® vaccine was found to be safe and immunogenic in toddlers and supported its further clinical development in infants. Clinical Trial Registration – CTRI/2019/11/022052. •Combination vaccines simplify vaccination schedules and improve compliance.•HEXASIIL® vaccine was compared to licensed DTwP-HepB-Hib + IPV vaccines.•HEXASIIL® had good safety and immunogenicity profile.•The data supported further evaluation of HEXASIIL® in infants.

This first in human study was designed as an open label clinical trial to assess the safety and tolerability of Serum Institute of India Pvt. Ltd. (SIIPL) Tdap vaccine in healthy adult volunteers, aged 18–45 years. A total of 24 healthy adults were administered a 0.5 ml single dose of SIIPL Tdap vaccine intramuscularly, and were followed for one month for safety outcomes viz., immediate, solicited, unsolicited and serious adverse events. 23 subjects completed the study in compliance with the study protocol. None of the participants experienced any immediate adverse events or any local or systemic solicited adverse events. Tdap vaccine manufactured by Serum Institute of India Pvt. Ltd. is safe and well tolerable in adults. It was concluded that further clinical development of this vaccine should continue to assess its safety and immunogenicity, in the target population. Clinical Trial Registration – CTRI/2017/03/008003.

Objective: The research was carried out to develop a validated analytical method for assessing the biogenic amines metabolites Vanillyl mandelic acid (VMA) and Homovanillic acid (HVA) simultaneously in biological fluids by High performance liquid chromatography- Photodiode Array (HPLC-PDA). Method: An HPLC technique was developed and validated for the measurement of VMA and HVA in artificial urine samples. The chromatographic separation was achieved on a Kromasil C8, 5µm (125 X 4.6 mm) column at 250C with combination of mobile phase of acetonitrile: 0.1 % o-phosphoric acid (30:70 v/v), flow rate of 0.9 mL/min using an Shimadzu HPLC system with LC Solutions liquid chromatography software. Different mobile phases were used on a trial and error basis to separate these two metabolites. Validation of ICH parameters in terms of linearity, accuracy, repeatability, precision, and robustness of methodology was performed. Result: The separation of vanillyl mandelic acid and homovanillic acid was achieved using a highresolution HPLC technique. The linearity range for VMA and HVA was selected from 10 µg/mL to 60 µg/mL, and were found to be linear, with coefficients of determination (r2) of 0.996 and 0.990 for both metabolites, respectively. The detection limits for VMA and HVA were 1.96 µg/mL and 1.31 µg/mL, respectively, with quantification limits of 5.96 µg/mL and 3.97 µg/mL. For repeatability, precision, and robustness parameters, the results demonstrated a low percent RSD value. Conclusion: A validated HPLC-PDA approach was developed for quantifying Vanillyl mandelic acid and Homovanillic acid in urine samples.

Research involving the pediatric population is essential if children are to reap the full benefits derived from advances in medical science. However, children represent a vulnerable population and thus, research with adults cannot simply be generalized or extrapolated to a pediatric population. To study this gap between adults and children for their well-being, disease prevention, diagnosis and treatment, high-quality clinical research is required. Therapeutic products that are likely to be of high clinical value in children need to be fully studied scientifically before their widespread use. Despite the need for high-quality clinical research in children, significant barriers exist, and there can be no clear-cut and easy answer that could be implemented overnight. This necessitates different approaches that fit an increasingly narrower medical profile of the pediatric population. This article describes various issues encountered by clinical studies in the pediatric population that remain to be solved.