Search

Tuberculosis is a major public health problem worldwide. Immunisation with Mycobacterium bovis BCG vaccine is partially effective in infants, reducing the incidence of miliary and tuberculosis meningitis, but is less effective against pulmonary tuberculosis. We aimed to compare safety and immunogenicity of VPM1002-a recombinant BCG vaccine developed to address this gap-with BCG in HIV exposed and HIV unexposed newborn babies.This double-blind, randomised, active controlled phase 2 study was conducted at four health centres in South Africa. Eligible neonates were aged 12 days or younger with a birthweight of 2·5-4·2 kg, and could be HIV exposed (seropositive mothers) or unexposed (seronegative mothers). Newborn babies were excluded if they had acute or chronic illness, fever, hypothermia, sepsis, cancer, or congenital malformation, or if they received blood products or immunosuppressive therapy. Participants were excluded if their mothers (aged ≥18 years) had active tuberculosis disease, diabetes, a history of immunodeficiency except for HIV, hepatitis B or syphilis seropositivity, received blood products in the preceding 6 months, any acute infectious disease, or any suspected substance abuse. Participants were randomly assigned to VPM1002 or BCG vaccination in a 3:1 ratio, stratified by HIV status using the random number generator function in SAS, using a block size of eight paticipants. The primary outcome was non-inferiority (margin 15%) of VPM1002 to BCG vaccine in terms of incidence of grade 3-4 adverse drug reactions or ipsilateral or generalised lymphadenopathy of 10 mm or greater in diameter by 12 months. The primary outcome was assessed in all vaccinated participants (safety population) at regular follow-up visits until 12 months after vaccination. Secondary immunogenicity outcomes were interferon-γ levels and percentages of multifunctional CD4sup+/supand CD8sup+/supT cells among all lymphocytes across the 12 month study period. The study was registered with ClinicalTrials.gov, NCT02391415.Between June 4, 2015 and Oct 16, 2017, 416 eligible newborn babies were randomly assigned and received study vaccine. Seven (2%) of 312 participants in the VPM1002 group had a grade 3-4 vaccine-related adverse reaction or lymphadenopathy of 10 mm or greater in diameter compared with 34 (33%) of 104 participants in the BCG group (risk difference -30·45% [95% CI -39·61% to -21·28%]; psubnon-inferiority/sublt;0·0001); VPM1002 was thus non-inferior to BCG for the primary outcome. Incidence of severe injection site reactions was lower with VPM1002 than BCG: scarring occurred in 65 (21%) participants in the VPM1002 group versus 77 (74%) participants in the BCG group (plt;0·0001); ulceration occurred in one (lt;1%) versus 15 (14%; plt;0·0001); and abscess formation occurred in five (2%) versus 23 (22%; plt;0·0001). Restimulated IFNγ concentrations were lower in the VPM1002 group than the BCG group at week 6, week 12, month 6, and month 12. The percentage of multifunctional CD4sup+/supT cells was higher in the VPM1002 group than the BCG group at day 14 but lower at week 6, week 12, month 6, and month 12. The percentage of multifunctional CD8sup+/supT cells was lower in the VPM1002 group than the BCG group at week 6, week 12, and month 6, but did not differ at other timepoints.VPM1002 was less reactogenic than BCG and was not associated with any serious safety concern. Both vaccines were immunogenic, although responses were higher with the BCG vaccine. VPM1002 is currently being studied for efficacy and safety in a multicentric phase 3 clinical trial in babies in sub-Saharan Africa.Serum Institute of India.

A lyophilized bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, Rotasiil®) was licensed in 2016. A liquid formulation of this vaccine (LBRV-PV, Rotasiil - Liquid) was subsequently developed and was tested for non-inferiority to Rotasiil® and for lot-to-lot consistency.This Phase II/III, open label, randomized study was conducted at seven sites across India from November 2017 to June 2018. Participants were randomized into four arms; Lots A, B, and C of LBRV-PV and Rotasiil® in 1:1:1:1 ratio. Three doses of study vaccines were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. Non-inferiority of LBRV-PV to Rotasiil was proven if the lower limit two-sided 95% confidence interval (CI) of geometric mean concentration (GMC) ratio was at least 0.5. Lot-to-lot consistency was proven if 95% CI of the GMC ratios of three lots were between 0.5 and 2. Solicited reactions were collected by using diary cards.Of the 1500 randomized infants, 1436 infants completed the study. The IgA GMC ratio of LBRV-PV to Rotasiil® was 1.19 (95% CI 0.96, 1.48). The corresponding IgA seropositivity rates were 60.41% (57.41, 63.35) and 52.75% (47.48, 57.97). The IgA GMC ratios among the three LBRV-PV lots were: Lot A versus Lot B: 1.34 (1.03, 1.75); Lot A versus Lot C: 1.22 (0.93, 1.60); and Lot B versus Lot C: 0.91 (0.69, 1.19). The 95% CIs for the GMC ratios were between 0.69 and 1.75. The incidence of solicited reactions was comparable across the four arms. Only one serious adverse event of gastroenteritis event in the Rotasiil® group was causally related.The immunological non-inferiority of LBRV-PV against Rotasiil® as well as lot-to-lot consistency of LBRV-PV was demonstrated. LBRV-PV had safety profile similar to Rotasiil®.Clinical Trials.Gov [NCT03474055] and Clinical Trial Registry of India [CTRI/2017/10/010104].

Background: ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at Serum Institute of India Pvt Ltd (SIIPL) after technology transfer from AstraZeneca, was evaluated in this phase 2/3 immunobridging study. Methods: This observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). Two doses of vaccine (5 × 10¹⁰ viral particles) or placebo were given at 4-week intervals (+2-week window). Primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibodies 28 days after second dose (defined as lower 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. Anti-spike IgG response was assessed using a validated multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Findings: Between August 25 and October 31, 2020, n=1601 participants were enrolled: n=401 to the immunogenicity/reactogenicity cohort and n=1200 to the safety cohort. After two doses of SII-ChAdOx1 nCoV-19 or AZD1222, seroconversion rates for anti-spike IgG antibodies were 98·0% and 98·9%, respectively, with anti-spike IgG GMTs of 30 245·6 AU/mL (95% CI 26 794·0–34 141·8) and 28 558·3 AU/mL (23 479·3–34 735·8); SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·79–1·23). SAEs were reported in 15/1200 (1·3%, 95% CI 0·7–2·1), 2/300 (0·7%, 0·1–2·4) and 2/100 (2·0%, 0·2–7·0) participants who received SII-ChAdOx1 nCoV-19, placebo and AZD1222, respectively; none were causally related. SARS-CoV-2 infections were observed in 1·9% (n=22), 3·4% (n=10) and 2·0% (n=2) of the SII-ChAdOx1 nCoV-19, placebo and AZD1222 groups, respectively; none were severe. Interpretation: SII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Trial Registration: This study was registered with number CTRI/2020/08/027170 Funding: SIIPL, Indian Council of Medical Research, AstraZeneca. Declaration of Interest: PSK, CB, AD, MG, US, DK, and BG are employees of SIIPL. JV and EJK are employees of AstraZeneca. All other authors declare no competing interests. Ethical Approval: The study was approved by the Drugs Controller General of India (DCGI) and the ethics committees of each study site.

At the instant, most of the attendance systems that are getting used in universities still are written a bit of paper. For classes, tutorials, and laboratory sessions the students still have got to sign the signature on the attendance sheet. This method isn't flexible because the danger of losing the attendance data is extremely high. If the attendance sheet is missing, the attendance data are going to be lost. Aside from that, the unethical problems could also be occurring like cheating in the signature. For instance, a student doesn't attend his class but his attendance form has been signed by another student. This technique is proposed to beat these problems. Besides that, since the proposed system also records the time, the lecturer can monitor the punctuality of the students too. “SMART ATTENDANCE SYSTEM” may be a system that will take attendance by using information extracted from the fingerprint Database Handling System. Before this lecturer must use the paper to urge the student’s attendance. There have been tons of problems when using the paper as student attendance like cheating. This system can help the lecturer to scale back the matter like that intentionally automatic attendance using fingerprint.

Background This phase 2/3 immunobridging study evaluated the safety and immunogenicity of the ChAdOx1 nCoV-19 Coronavirus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at the Serum Institute of India Pvt Ltd (SIIPL), following technology transfer from the AstraZeneca. Methods This participant-blind, observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). The study participants were enrolled from 14 hospitals across India between August 25 and October 31, 2020. Two doses of study products were given 4 weeks apart. The primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike IgG antibodies 28 days after the second dose (defined as lower limit of 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. The anti-spike IgG response was assessed using a multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Trial registration: CTRI/2020/08/027170. Findings 1601 participants were enrolled: 401 to the immunogenicity/reactogenicity cohort and 1200 to the safety cohort. After two doses, seroconversion rates for anti-spike IgG antibodies were more than 98·0% in both the groups. SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·78–1·23). SAEs were reported in ≤ 2·0% participants across the three groups; none were causally related. A total of 34 SARS-CoV-2 infections were reported; of which 6 occurred more than 2 weeks after the second dose; none were severe. Interpretation SII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Pharmacovigilance should be maintained to detect any safety signals. Funding SIIPL funded the contract research organisation and laboratory costs, while the site costs were funded by the Indian Council of Medical Research. The study vaccines were supplied by SIIPL and AstraZeneca.

Background Measles is a highly infectious respiratory disease which causes 122,000 deaths annually. Although measles vaccine is extremely safe and effective, vaccine coverage could be improved by a vaccine that is more easily administered and transported. We developed an inhalable dry powder measles vaccine (MVDP) and two delivery devices, and demonstrated safety, immunogenicity, and efficacy of the vaccine in preclinical studies. Here we report the first clinical trial of MVDP delivered by inhalation. Methodology Sixty adult males aged 18 to 45 years, seropositive for measles antibody, were enrolled in this controlled Phase I clinical study. Subjects were randomly assigned in 1:1:1 ratio to receive either MVDP by Puffhaler® or by Solovent™ devices or the licensed subcutaneous measles vaccine. Adverse events (AEs) were recorded with diary cards until day 28 post-vaccination and subjects were followed for 180 days post-vaccination to assess potential serious long term adverse events. Measles antibody was measured 7 days before vaccination and at days 21 and 77 after vaccination by ELISA and a plaque reduction neutralization test. Results All subjects completed the study according to protocol. Most subjects had high levels of baseline measles antibody. No adverse events were reported. MVDP produced serologic responses similar to subcutaneous vaccination. Conclusions MVDP was well tolerated in all subjects. Most subjects had high baseline measles antibody titer which limited ability to measure the serologic responses, and may have limited the adverse events following vaccination. Additional studies in subjects without pre-existing measles antibody are needed to further elucidate the safety and immunogenicity of MVDP.

A bovine rotavirus pentavalent vaccine (BRV-PV) containing rotavirus human-bovine (UK) reassortant strains of serotype G1, G2, G3, G4 and G9 has been developed by the Serum Institute of India Ltd, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), USA. The vaccine underwent animal toxicity studies and Phase I and II studies in adults, toddlers and infants. It has been found safe and immunogenic and will undergo a large Phase III study to assess efficacy against severe rotavirus gastroenteritis.

a b s t r a c t Major epidemics of serogroup A meningococcal meningitis continue to affect the African meningitis belt. The development of an affordable conjugate vaccine against the disease became a priority for World Health Organization (WHO) in the late 1990s. Licensing of meningococcal vaccines has been based on serological correlates of protection alone, but such correlates might differ in different geographical regions. If high pre-vaccination antibody concentrations/titers impacts on the response to vaccination and possibly vaccine efficacy, is not clearly understood. We set out to define the pre-vaccination Meningo- coccal group A (Men A) antibody concentrations/titers in The Gambia and study their impact on the immunogenicity of Men A containing vaccines. Data from subjects originally enrolled in studies to test the safety and immunogenicity of the MenA vaccine recently developed for Africa meningococcal A polysaccharide conjugated to tetanus toxoid, MenAfriVac ® (PsA-TT) were analyzed. Participants had been randomized to receive either the study vaccine PsA-TT or the reference quadrivalent plain polysaccharide vaccine containing meningococcal groups A, C, W, and Y, Mencevax ® ACWY, GlaxoSmithKline (PsACWY) in a 2:1 ratio. Venous blood sam- ples were collected before and 28 days after vaccination. Antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) for geometric mean concentrations and serum bactericidal antibody (SBA) for functional antibody. The inter age group differences were compared using ANOVA and the pre and post-vaccination differences by t test. Over 80% of the ≥19 year olds had pre-vaccination antibody concentrations above putatively protective concentrations as compared to only 10% of 1-2 year olds. Ninety-five percent of those who received the study vaccine had ≥4-fold antibody responses if they had low pre-vaccination concentrations compared to 76% of those with high pre-vaccination concentrations. All subjects with low pre-vaccination titers attained ≥4-fold responses as compared to 76% with high titers where study vaccine was received. Our data confirm the presence of high pre-vaccination Men A antibody concentrations/titers within the African meningitis belt, with significantly higher concentrations in older individuals. Although all partic- ipants had significant increase in antibody levels following vaccination, the four-fold or greater response in antibody titers were significantly higher in individuals with lower pre-existing antibody titers, espe- cially after receiving PsA-TT. This finding may have some implications for vaccination strategies adopted in the future.

In the event of a highly pathogenic influenza pandemic, the Indian subcontinent would need 1.2 billion doses of vaccine to immunize its entire population, double if two doses were required to assure immunity. Serum Institute of India Limited (SII) thus became one of six initial grantees of the World Health Organization (WHO) technology transfer initiative to create capacity in developing countries to manufacture H5N1 pandemic influenza vaccine. At the outbreak of the A(H1N1) 2009 influenza pandemic, experience gained from the H5N1 project was used to develop a live attenuated influenza vaccine (LAIV), since this was the only option for the level of surge capacity required for a large-scale immunization campaign in India. SII took

We performed a double-blind, randomized, controlled phase I study to assess safety, immunogenicity, and antibody persistence of the new meningococcal group A conjugate vaccine (PsA-TT) in healthy volunteers aged 18–35 years. Of the 74 male subjects enrolled, 24 received the PsA-TT vaccine (Group 1), 25 received the Meningoccoccal Polysaccharide Vaccine A + C™, Pasteur, Lyon, France (Group 2), and 25 received the Tetanus Toxoid Vaccine Adsorbed™, SIIL, Pune India (Group 3). No immediate reactions were observed. Local and systemic solicited reactions within 7 days post-vaccination and unsolicited adverse events (AEs) were mild and similar among the three groups and resolved without sequelae. No serious AEs were notified up to 1 year post-vaccination. Four weeks post-vaccination, a slightly higher proportion of Group 1 subjects had a four-fold increase in SBA titers compared to Group 2 subjects (83% versus 72%, p > 0.05). SBA GMTs in Groups 2 and 3 were higher than in Group 3 (p < 0.05). Serogroup A-specific IgG GMCs were significantly higher in Group 1 than in Groups 2 (p < 0.05) and 3 (p < 0.05). After 1 year SBA titers were significantly higher in Group 1 than in Group 2 (p < 0.05). The new PsA-TT vaccine was shown to be safe, immunogenic, and able to elicit persistent functional antibody titers in adults. This opens the prospective for further development and licensure of this vaccine to eliminate epidemic meningitis in sub-Saharan Africa.

An alum adjuvanted whole virion inactivated vaccine against the A (H1N1) 2009 pandemic virus was developed in India. Two double-blind, randomized studies were conducted. Fifty adults (18–50 years) were enrolled in the Phase I study, whereas the Phase II/III study consisted of 330 adults (≥18 years) and children ≥3 years. Safety (both studies) and immunogenicity (Phase II/III study) by hemagglutination inhibition (HI) antibody titers, of 10 μg or 15 μg of hemagglutinin (HA) antigen were compared. In the Phase I study, mostly mild and transient injection site and systemic reactions were reported. Similar events were seen in the Phase II/III study. The overall seroprotection was 96% and 89% with 10 and 15 μg doses, respectively, while the seroconversion was 92% and 88%. The new Indian-made pandemic H1N1 vaccine is safe and immunogenic in adults and children above 3 years of age.

Purpose: To report the association of anterior uveitis with the use of latanoprost. Methods: We studied four patients with complicated open-angle glaucoma who had anterior uveitis associated with the use of latanoprost. The uveitis was unilateral and occurred only in the eye receiving latanoprost in three patients. In one patient, latanoprost was used in both eyes, and the uveitis was bilateral. Four of five eyes had a history of prior inflammation and/or prior incisional surgery. All patients were rechallenged with the drug. Results: The uveitis improved after cessation of latanoprost with or without topical corticosteroids. It recurred after rechallenging with latanoprost in all eyes. Conclusion: There is a possible association between latanoprost and anterior uveitis. Topical prostaglandin analogs may be relatively contraindicated in patients with a history of uveitis or prior ocular surgery. This association may also be possible in eyes that have not had previous uveitis or incisional surgery.

The study by da Cunha et al. published in 2002 reported that MMR vaccine containing L-Zagreb mumps strain manufactured by Serum Institute of India Ltd. caused a high incidence of aseptic meningitis (AM) from routine surveillance during two mass immunization campaigns (MIC) conducted in 1998 in two states in Brazil. Since the results were contrary to those in India, Egypt and Bahamas, a critical analysis of the study was done. Several inconsistencies were found in the study, which undermined the conclusions drawn. Two similar studies from Brazil reported similar results. Review of these studies and those done on the vaccine from Zagreb, Croatia showed that in no study the L-Zagreb mumps virus has been isolated from cerebrospinal fluid (CSF) of an AM case. Isolation of the vaccine virus is necessary for definite causal association of AM with the vaccine. There is no such evidence to causally link MMR vaccine containing L-Zagreb mumps strain with AM.

Indomethacin-treated bovine iris-ciliary body microsomes (IBIM) have been studied for their ability to convert PG endoperoxides into either thromboxane-A2 (TxA2)-like or prostacyclin (PGI2)-like activity. The biological activity of the ocular tissue microsomes were compared with either indomethacin-treated human platelet microsomes (for TxA2-like activity) or rabbit aorta microsomes (for PGI2-like activity) under appropriate incubation conditions. No evidence could be found for the formation of TxA2-like activity from PG endoperoxides by the IBIM. In contrast, when the IBIM were incubated with PGH2 for 1 min at 22 degrees C without cofactors, PGI2-like activity was produced, causing profound relaxation of the isolated dog coronary artery preparation without contracting the rabbit aorta and inhibiting arachidonic acid-induced platelet aggregation. Equivalent quantities of boiled IBIM failed to alter the biological activity of PGH2 under identical conditions. Tranylcypromine (500 microgram/ml) completely abolished the appearance of PGI2-like activity. Furthermore, the PGI2-like activity found was stable for 10 min at 22 degrees C at pH 8.5 but completely lost under similar conditions at pH 5.5. It is concluded that microsomal preparations of normal bovine iris-ciliary body can synthesize PGI2-like activity in substantial amounts but not TxA2-like activity.