Explore the vast range of titles available.

This is a comprehensive report on immunogenicity of COVAXIN ® booster dose against ancestral and Variants of Concern (VOCs) up to 12 months. It is well known that neutralizing antibodies induced by COVID-19 vaccines wane within 6 months of vaccination leading to questions on the effectiveness of two-dose vaccination against breakthrough infections. Therefore, we assessed the persistence of immunogenicity up to 6 months after a two or three-dose with BBV152 and the safety of a booster dose in an ongoing phase 2, double-blind, randomized controlled trial (ClinicalTrials.gov: NCT04471519). We report persistence of humoral and cell mediated immunity up to 12 months of vaccination, despite decline in the magnitude of antibody titers. Administration of a third dose of BBV152 increased neutralization titers against both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, Delta Plus and Omicron) with a slight increase in B cell memory responses. Thus, seronversion rate remain high in boosted recipients compared to non-booster, even after 6 months, post third dose against variants. No serious adverse events observed, except pain at the injection site, itching and redness. Hence, these results indicate that a booster dose of BBV152 is safe and necessary to ensure persistent immunity to minimize breakthrough infections of COVID-19, due to newly emerging variants. Trial registration: Registered with the Clinical Trials Registry (India) No. CTRI/2021/04/032942, dated 19/04/2021 and on Clinicaltrials.gov: NCT04471519.

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin®. Between April 16 and June 4, 2022, we enrolled 3160 subjects of whom, 2971 received 2 doses of BBV154 and 161 received Covaxin. On Day 42, 14 days after the second dose, BBV154 induced significant serum neutralization antibody titers against the ancestral (Wuhan) virus, which met the pre-defined superiority criterion for BBV154 over Covaxin®. Further, both vaccines showed cross protection against Omicron BA.5 variant. Salivary IgA titers were found to be higher in BBV154. In addition, extensive evaluation of T cell immunity revealed comparable responses in both cohorts due to prior infection. However, BBV154 showed significantly more ancestral specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients showed significant Omicron specific IgA-secreting plasmablasts only at day 42. Both vaccines were well tolerated. Overall reported solicited reactions were 6.9% and 25.5% and unsolicited reactions were 1.2% and 3.1% in BBV154 and Covaxin® participants respectively.

Aims The ICMR INDIAB-17 study revealed a diabetes prevalence of 11.4% in India, emphasizing the need for effective treatment for glycemic control. A Phase IV study was conducted to evaluate the safety and efficacy of a Fixed Dose Combination (FDC) of Remogliflozin, Metformin and Vildagliptin (RMV) in Type 2 Diabetes Mellitus (T2DM) patients uncontrolled on Metformin plus SGLT2 inhibitor or Metformin plus DPP4 inhibitor dual therapy. Methods A total of 215 patients (mean age: 46.4 years; 64% male, 36% female) were enrolled across multiple centers in India. The study population included patients with a baseline HbA1c ≥ 8% at the time of screening. The primary objective was to assess safety based on treatment-emergent adverse events (TEAEs), while the secondary. aim was to evaluate effectiveness in terms of glycemic (HbA1c, fasting plasma glucose, postprandial glucose) and extra-glycemic measures (renal and lipid parameters). Statistical analysis was conducted using paired t-tests and the Wilcoxon signed-rank test for within-group comparisons, and the Bonferroni correction was applied to adjust for multiple comparisons. Effectiveness was evaluated at baseline, week 12, and week 24. Results The study demonstrated statistically significant reductions in mean HbA1c levels from baseline to both week 12 and week 24 ( p  < 0.00001). At 24, weeks, 45.1% of patients achieved target HbA1c levels of ≤ 7%. Significant reduction was also observed in fasting plasma glucose (FPG) and postprandial glucose (PPG) levels. Renal parameters remained stable or improved, and lipid profile parameters, including LDL-C and triglycerides, showed favorable changes. Adverse events of special interest, including hypoglycemia and urinary tract infections, were reported in 4.7% of patients, with no serious adverse event recorded. Conclusions The twice daily triple FDC of RMV was well tolerated, safe and effective in patients with Type 2 Diabetes Mellitus uncontrolled on dual drug therapy of Metformin plus SGLT2i or Metformin plus DPP4i. The treatment led to significant improvements in glycemic control and other metabolic parameters over 24 weeks, without compromising renal function or causing serious adverse events. Trial registration CTRI, CTRI/2022/05/042581. Registered 17 May 2022, https//ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=68,757&EncHid=36127.16500&modid=1&compid=19.

Background Due to waning immunity and emerging variants, protection following primary intramuscular Covid-19 vaccinations is decreasing, so health agencies have been proposing heterologous booster vaccinations. Here, we report immunogenicity and safety evaluation of heterologous booster vaccination with an intranasal, adenovirus vectored SARS-CoV-2 vaccine (BBV154) in healthy adults, who were previously primed with two doses of either Covaxin® or Covishield™. We compare results with use of a homologous booster vaccination combination. Methods This was a randomized, open-label phase 3 trial conducted to evaluate immunogenicity and safety of a booster dose of intranasal BBV154 vaccine or intramuscular EUA approved Covid-19 vacines in India. Healthy participants of ≥18 years age with no history of SARS-CoV-2 infection, who received two doses of Covaxin ® or Covishield™ at least 6 ± 1 months earlier were enrolled. The primary outcome was the neutralising antibody titers against wild-type virus using a plaque-reduction neutralization test (PRNT 50 ). Other outcomes measured were humoral (IgG), mucosal (IgA) and cell mediated responses. The protocol was registered #NCT05567471 and approved by National Regulatory Authority (India) #CTRI/2022/02/039992. Results In this phase 3 trial, a total of 875 participants were randomized into 5 Groups in a ratio of 2:1:2:1:1 to receive either booster dose of BBV154 or Covaxin or Covishield. Based on per-protocol population, at Day 56, neutralization antibody titres were 564.1 (479·1, 664·1), 578.1 (436·9, 764·9), 655.5 (533·3, 805·8), 625.4 (474·7, 824·0), 650.1 (519·7, 813·1) for Group 1 to 5 respectively. This study was conducted, whilst the Omicron variant was prevalent. There were varying levels of severity of infection across different study sites with varied baseline antibody titers. Consequently, the average neutralization (PRNT 50 ) antibody titers are similar across all Groups on day 56 and exhibited large differences within the Group, depending on the study site. All booster vaccinations are well tolerated and reported no serious adverse events; in particular, study participants boosted with BBV154 had significantly fewer solicited local adverse events than those primed and boosted with Covishield. Conclusions These findings demonstrate that impact of booster across different cohorts is governed by infection status of the individual and geographical diversity, thus necessitating large cohorts, well distributed studies before Covid-19 booster effects are interpreted. Plain language summary We undertook a clinical trial to compare the booster dose effect of two currently used COVID vaccines (Covaxin® or Covishield™), with a newly developed intranasal COVID vaccine. The booster dose was given 6 months after two initial doses of COVID vaccines. We measured levels of antibodies, which are proteins that help the body to identify and destroy the SARS-CoV-2 virus following vaccination. The effect on antibodies was similar for all vaccination groups, whilst with the new vaccine there were fewer adverse events. This data, combined with the ease of administration, confirms that our new intranasal vaccine is safe and effective and can therefore be included in vaccination programs for COVID-19. Venkateshwar et al., explored the effect of Heterologous intranasal iNCOVACC® vaccination as a booster to two-dose intramuscular Covid-19 vaccinations (either by Covishield or Covaxin) in a controlled, randomised, open-label phase 3 clinical trial. This study also aimed to compare these results with homologous booster vaccinations by Covishield or Covaxin.

BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 μg or 6 μg) formulated with a toll-like receptor 7/8 agonist molecule (IMDG) adsorbed to alum (Algel). We previously reported findings from a double-blind, multicentre, randomised, controlled phase 1 trial on the safety and immunogenicity of three different formulations of BBV152 (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) and one Algel-only control (no antigen), with the first dose administered on day 0 and the second dose on day 14. The 3 μg and 6 μg with Algel-IMDG formulations were selected for this phase 2 study. Herein, we report interim findings of the phase 2 trial on the immunogenicity and safety of BBV152, with the first dose administered on day 0 and the second dose on day 28. We did a double-blind, randomised, multicentre, phase 2 clinical trial to evaluate the immunogenicity and safety of BBV152 in healthy adults and adolescents (aged 12–65 years) at nine hospitals in India. Participants with positive SARS-CoV-2 nucleic acid and serology tests were excluded. Participants were randomly assigned (1:1) to receive either 3 μg with Algel-IMDG or 6 μg with Algel-IMDG. Block randomisation was done by use of an interactive web response system. Participants, investigators, study coordinators, study-related personnel, and the sponsor were masked to treatment group allocation. Two intramuscular doses of vaccine were administered on day 0 and day 28. The primary outcome was SARS-CoV-2 wild-type neutralising antibody titres and seroconversion rates (defined as a post-vaccination titre that was at least four-fold higher than the baseline titre) at 4 weeks after the second dose (day 56), measured by use of the plaque-reduction neutralisation test (PRNT50) and the microneutralisation test (MNT50). The primary outcome was assessed in all participants who had received both doses of the vaccine. Cell-mediated responses were a secondary outcome and were assessed by T-helper-1 (Th1)/Th2 profiling at 2 weeks after the second dose (day 42). Safety was assessed in all participants who received at least one dose of the vaccine. In addition, we report immunogenicity results from a follow-up blood draw collected from phase 1 trial participants at 3 months after they received the second dose (day 104). This trial is registered at ClinicalTrials.gov, NCT04471519. Between Sept 5 and 12, 2020, 921 participants were screened, of whom 380 were enrolled and randomly assigned to the 3 μg with Algel-IMDG group (n=190) or 6 μg with Algel-IMDG group (n=190). Geometric mean titres (GMTs; PRNT50) at day 56 were significantly higher in the 6 μg with Algel-IMDG group (197·0 [95% CI 155·6–249·4]) than the 3 μg with Algel-IMDG group (100·9 [74·1–137·4]; p=0·0041). Seroconversion based on PRNT50 at day 56 was reported in 171 (92·9% [95% CI 88·2–96·2] of 184 participants in the 3 μg with Algel-IMDG group and 174 (98·3% [95·1–99·6]) of 177 participants in the 6 μg with Algel-IMDG group. GMTs (MNT50) at day 56 were 92·5 (95% CI 77·7–110·2) in the 3 μg with Algel-IMDG group and 160·1 (135·8–188·8) in the 6 μg with Algel-IMDG group. Seroconversion based on MNT50 at day 56 was reported in 162 (88·0% [95% CI 82·4–92·3]) of 184 participants in the 3 μg with Algel-IMDG group and 171 (96·6% [92·8–98·8]) of 177 participants in the 6 μg with Algel-IMDG group. The 3 μg with Algel-IMDG and 6 μg with Algel-IMDG formulations elicited T-cell responses that were biased to a Th1 phenotype at day 42. No significant difference in the proportion of participants who had a solicited local or systemic adverse reaction in the 3 μg with Algel-IMDG group (38 [20·0%; 95% CI 14·7–26·5] of 190) and the 6 μg with Algel-IMDG group (40 [21·1%; 15·5–27·5] of 190) was observed on days 0–7 and days 28–35; no serious adverse events were reported in the study. From the phase 1 trial, 3-month post-second-dose GMTs (MNT50) were 39·9 (95% CI 32·0–49·9) in the 3μg with Algel-IMDG group, 69·5 (53·7–89·9) in the 6 μg with Algel-IMDG group, 53·3 (40·1–71·0) in the 6 μg with Algel group, and 20·7 (14·5–29·5) in the Algel alone group. In the phase 1 trial, BBV152 induced high neutralising antibody responses that remained elevated in all participants at 3 months after the second vaccination. In the phase 2 trial, BBV152 showed better reactogenicity and safety outcomes, and enhanced humoral and cell-mediated immune responses compared with the phase 1 trial. The 6 μg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial. Bharat Biotech International. For the Hindi translation of the abstract see Supplementary Materials section.

The sensitivity of simulation of the diurnal cycle (DC) to cumulus parameterisation is studied by using nine combinations (3 over Ocean × 3 over land) of cumulus schemes viz. Tiedtke, Emanuel, and Grell schemes for years 2008–2012 in the regional climate model RegCM4.4. The harmonic analysis is used to analyze the DC of rainfall simulated by the nine combinations of CPSs. It is seen that Emanual scheme predicts the spatial distribution of amplitude of the first harmonic and the variance of the diurnal cycle more appropriately compared to other CPSs. However, all schemes advanced the phase of the DC of rainfall by 3–6 h which is the result of the development of early convection in the model. The analysis of the development of rapid convection in the model suggests that sensible heat flux and vertically integrated moisture flux convergence peaks 3 to 6 h earlier compared to the phase of DC of rainfall estimated from TRMM rainfall. The early development of convection in the model may result in the inappropriate representation of condensation and evaporation cycle and hence DC of rainfall. The study emphasize that improvement in the phase of triggering of convection by cumulus parameterization schemes is essential to improve DC rainfall simulated by regional climate models.

Herpes (varicella) zoster (HZ) infection occurs in 4 people per 1000 in the general US population (irrespective of prior varicella infection and vaccination status) each year and has been the subject of scientific inquiry for decades. The consequences of infection are myriad and may depend on the dermatome of involvement as well as host factors such as age, comorbidities, prior treatment or immunization, and immunologic status. Pregnancy is associated with an altered immune and hormonal status in the mother. While maternal HZ infection during pregnancy is not uncommon, the implications for both mother and child are not well established, although multiple studies of perinatal maternal HZ infection suggest no intrauterine transmission to the fetus. We review the current literature on herpes zoster infection in pregnancy, including epidemiology, diagnosis, potential immunologic sequelae, and strategies for prevention and treatment.

Clouds modulate the infrared radiation absorption and shortwave radiation reflection in the atmosphere. Infrared absorption inside the cloud generates turbulence and alters the hydrometeor energy distribution. Therefore, it is imperative to parameterize changes in heat, specific vertical momentum, and vertical velocity in microphysical models. This paper aims to parameterize the impact of infrared absorption/heating on vertical velocity inside the cloud for stratiform rainfall on 01-Sep-2019 over Gadanki, India. The line-by-line spectroscopic parameters were obtained from the HITRAN dataset, and the absorption coefficients from surface to 280 hPa have been calculated. Specific moist entropy and advection–diffusion equations have been solved to estimate changes in temperature, moist entropy, specific vertical momentum, and vertical velocity. Results show that infrared heating/cooling (IRH/C) caused a temperature increase (decrease) below (above) 700 hPa. It also caused a negative (positive) change in moist entropy below (above) 700 hPa, which strengthened (suppressed) cloud growth in the lower (upper) layers of the cloud. Change in specific vertical momentum found to be negative, i.e., downdraft/downward momentum transfer below 700 hPa till cloud bottom, and positive, i.e., updraft/upward momentum transfer above 700 hPa till cloud top. The study showed that IRH/C substantially impacts the vertical velocity inside the cloud.Research highlightsThe parameterization for estimating the impact of infrared heating and cooling on stratiform cloud evolution has been developed.HITRAN spectroscopic parameters have been used to estimate the vertical profile of infrared radiative properties in the atmosphere.Infrared heating/cooling restricts the cloud’s vertical structure by controlling most of the entropy and vertical momentum transfer.The heating/cooling perturbs moist entropy either to positive or negative values, implying evaporation (growth) or melting (decay) of hydrometeors inside the clouds.Infrared heating/cooling significantly perturb the vertical velocity, i.e., updrafts/downdrafts, and hence hydrometeor distribution inside the cloud.

The collection mechanism inside the cloud is associated with the coalescence process. It controls the rainfall rate in the presence of high moisture content and low cloud condensation nuclei concentrations. The effectiveness of the coalescence mechanism is determined by the magnitude of the coalescence efficiency. This study compared the effectiveness of six coalescence efficiencies to identify the appropriate formulation, which can simulate the cloudburst event of 10 June 2021 over Sauni Binsar, Uttarakhand, at 11:45 IST (06:15 UTC). The coalescence efficiencies have been estimated between the lifting condensation levels and freezing levels over 100 equidistance intervals, with variation in the bins of colliding droplet pairs. The comparative analysis shows that Ochs’s formulation estimated high values of coalescence efficiencies ranging between 60 and 100% for all bins of droplet diameters during the cloudburst event. The maximum values of coalescence efficiency were found to be high for small cloud droplet diameter of 1–100 µm for collector droplet diameter of 50–7000 µm. The estimates provided by Seifert and Chen and Liu were below 80%, while Low and List, Beard and Ochs estimated coalescence efficiency values of up to 70% for all-collector cloud droplet diameters and small cloud droplet diameters. However, the estimated coalescence efficiencies by Brazier–Smith formulation are very low, not exceeding 20%, for all collector cloud droplet diameters and small cloud droplet diameters. The selection of appropriate coalescence parametrization is essential for appropriately simulating rainfall intensities using microphysics parametrization during extreme weather events. Research highlights The coalescence process plays an important role in determining rain rate, and modelling it is a challenge. Six coalescence efficiencies have been estimated for the cloud burst event of Sauni Binsar, Uttarakhand, India. Ochs’s formulation estimated high values of coalescence efficiencies ranging between 60 and 100% for all bins of droplet diameter, which was expected. Seifert and Chen and Liu formulations estimated coalescence efficiencies below 80%, and Low and List and Beard and Ochs estimated coalescence efficiency up to 70% for the all-collector cloud droplet diameter and small cloud droplet diameter. The estimated coalescence efficiencies by Brazier–Smith formulation are very low, not exceeding 20%.

Cloudburst events are characterized by very high rainfall rates (100 mm h −1 ) over a small area (~10×10 km). It catastrophically damages the properties and causes loss of lives. Therefore, it is essential to understand the nature of the microphysical processes that contributed to producing such a high rain rate. Collision processes inside the cloud are vital in determining the rainfall rate. Hence, in the present study, we have evaluated a comparative performance of disparate collision efficiencies based on different formulations during the cloud burst event of 10 June 2021 over Sauni Binsar, Uttarakhand, at 11:45 AM IST (06:15 UTC 10 June 2021). The lifting condensation level (LCL), lifting deposition level (LDL), and lifting freezing levels (LFL) have been calculated using the ERA5 dataset. The collision efficiencies were determined on 100 levels between the lifting condensation and freezing levels. The appraisal of eight formulations shows that Onishi, Beard and Grover, Bohm, and Jin formulations yielded higher collision efficiencies during the cloudburst event, which is expected. Meanwhile, the estimated collision efficiency based on Ahmad’s formulation is high for specific bins only. The formulations by Barnet, Long, and Lee and Baik, however, yielded very low values of collision efficiencies during the cloud burst event. Research highlights Collision processes inside the cloud are vital in determining the rainfall rates especially during cloud burst. Eight collision efficiency formulations have been apprised during the cloud burst event of Sauni Binsar, Uttarakhand, India. The complex interaction between synoptic systems and orography caused atmosphere over Sauni Binsar to be convective and moist few hours before the cloud burst event. Collision efficiency formulation by Onishi, Beard and Grover, Bohm, and Jin estimated higher collision efficiencies, which is appropriate, while Ahmad estimated high values for specific bins only. Collision efficiency formulation by Barnet, Long, and Lee and Baik estimated very low values.