Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Tuberisation Pattern of Tannia (Xanthosoma sagittifolium (L.) Schott) in Response to Crop Management Practices in the South Central Laterites (AEU 9) of Kerala, India

The study was conducted to outline the rooting and tuberisation pattern of tannia (Xanthosoma sagittifolium (L.) Schott) as influenced by different crop management practices. As an underutilised crop, it was uncertain as to the management techniques which would increase tuberisation and productivity levels of tannia. Hence the study was to promote tuberisation in tannia with a focus on the underground portions of the plant. The variation in rooting pattern was studied in terms of root number, root weight and root volume and the tuberisation pattern as number of cormels per plant, corm weight per plant, cormel weight per plant and rate of tuber bulking. The study was conducted in Kollam district under AEU (Agro Ecological Unit) 9 during the period from Feb 2021- Dec 2021. The experiment comprised three treatments in completely randomised design with six replications. The treatments were t1 - KAU POP (Kerala Agricultural University Package of Practices Recommendations), t2 - farmers’ practice and t3 - absolute control. The results revealed that, the root number (43.29), root weight (32.74 g plant-1) and the root volume (38.22 g plant-1) were significantly the highest in t1 (KAU POP) at harvest followed by farmers’ practice and absolute control. When considering the percentage increase in root production, KAU POP recorded 19.22 per cent, 8.79 per cent, 11.04 per cent and 15.66 per cent more number of roots at 4 MAP, 6 MAP, 8 MAP and harvest than farmers’ practice. The number of cormels per plant (12.16), corm weight per plant (563.16 g), cormel weight per plant (439.16 g) at harvest and the rate of tuber bulking (1.27 kg ha-1 d-1) at 4 to 5 MAP were found to be the highest with t1 followed by t2 and t3

TOXICOLOGICAL PROFILING OF METHANOLIC AND AQUEOUS EXTRACTS OF AMORPHOPHALLUS COMMUTATUS VAR. WAYANADENSIS - ENDANGERED MEDICINAL PLANT IN RODENT MODELS

Objective: Amorphophallus commutatus var. wayanadensis (ACW) is exclusive endemic of Wayanad has been used among the traditional medicinal healers of tribal communities of Wayanad for the treatment of various ailments. Our aim of the study is to evaluate the toxicity profile of ACW is by acute and sub-acute in rodents.  Methods: In acute toxicity studies, mice were orally administered of single doses of 1000 and 2000mg/kg of methanolic and aqueous extract and sub-acute toxicity studies were performed by administration of 200 and 400mg/kg orally for 28 days. Results: In acute toxicity studies, administration of methanolic and aqueous extract didn't observe any signs of mortality or toxicity upto 2000mg/kg body weight. No significant change in the physical, biochemical, hematological and histopathology analysis were observed for methanolic and aqueous extracts by sub-acute toxicity studies. Conclusion: The methanolic and aqueous extract of Amorphophallus commutatus var. wayanadensis is relatively safe for long term oral administration fulfilling the basic priority for its use in traditional medicinal therapies