Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India

Highly efficient organic-inorganic poly(3,4-ethylenedioxythiophene)-molybdenum trioxide nanocomposite electrodes for electrochemical supercapacitor

In this paper, we report a highly efficient organic-inorganic nanocomposite electrode with enhanced double layer capacitance, which has been synthesized using 3,4-ethylenedioxythiophene and crystalline molybdenum trioxide (MoO<SUB>3</SUB>) in the presence of an external oxidizing agent. The interlayer spacing of MoO<SUB>3</SUB> upon intercalation expands from 6.93 to 13.46 Å and is followed by an exfoliation and restacking process. The resulting nanocomposite is characterized by powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, x-ray photoelectron spectroscopy, and four probe conductivity measurements. The application potential of this nanocomposite as an electrode material for electrochemical supercapacitors has been investigated, highlighting the unusual enhancement of double layer capacitance of poly(3,4-ethylenedioxythiphene) (PEDOT-MoO<SUB>3</SUB>) nanocomposites ( ~300 F g<SUP>−1</SUP>) compared to that of pristine MoO<SUB>3</SUB> (~40 mF g<SUP>−1</SUP>). The improved electrochemical performance is attributed to the intercalation of electronically conducting PEDOT between MoO<SUB>3</SUB> layers with enhanced bidimensionality and an increase in the surface area

Enhancement of double-layer capacitance behavior and its electrical conductivity in layered poly (3, 4-ethylenedioxythiophene)-based nanocomposites

In this letter, we report on the enhanced double-layer capacitance of a layered poly (3, 4-ethylene dioxythiophene) PEDOT-MoO3 nanocomposite, which has been synthesized by a novel microwave irradiation method..

Structure, electronic structure, optical and dehydrogenation catalytic study of (Zn<SUB>1-z</SUB>ln<SUB>z</SUB>)(O<SUB>1-x</SUB>N<SUB>x</SUB>) solid solution

Indium and nitrogen codoping in ZnO leads to a solid solution of InN in ZnO with a composition of (Zn<SUB>1-z</SUB>ln<SUB>z</SUB>)(O<SUB>1-x</SUB>N<SUB>x</SUB>). A simple solution combustion method has been adopted to prepare the above materials in less than 10 min with metal nitrates as the metal ion source and urea as fuel. With reference to ZnO, significant increase in lattice parameters was observed with increasing In-content. However, the In<SUB>2</SUB>O<SUB>3</SUB> phase was observed along with InN for In content &#8805;10%. Optical absorption extended into the visible region, at least up to 550 nm, demonstrates an effective reduction of optical band gap due to the formation of solid solution. A new feature observed just above O 2p valence band in X-ray photoelectron spectroscopy (XPS) suggests the creation of N 2p states from InN; the N 1s core level XPS result too confirms nitride contribution. Raman spectroscopy and secondary ion mass spectrometry results show direct In-N, Zn-N, and In-N-Zn fragments in (Zn<SUB>1-z</SUB>ln<SUB>z</SUB>)(O<SUB>1-x</SUB>N<SUB>x</SUB>). Catalytic activity explored for oxidation of 2-butanol to ethyl methyl ketone demonstrates a high selectivity at 350 and 400 °C. All of the above characteristics suggest the multifunctional nature of (Zn<SUB>1-z</SUB>ln<SUB>z</SUB>)(O<SUB>1-x</SUB>N<SUB>x</SUB>) and its potential for other applications

Synthesis and characterization of organic-inorganic poly(3,4-ethylenedioxythiophene)/MoS2 nanocomposite via in situ oxidative polymerization.

Here we demonstrate the synthesis of a new type of layered poly(3,4-ethylenedioxythiophene) (PEDOT)/MoS2 nanocomposite via flocculation of delaminated MoS2 with subsequent in situ oxidative polymerization of 3,4-ethylenedioxythiophene..

The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial

Background Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). Methods In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry–India (CTRI/2022/06/043608) and is completed. Findings 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8–99·9) with Sii-PTCV and 100·0% (88·4–100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9–99·2) with Sii-PTCV and 100·0% (88·4–100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4–100·0) with Sii-PTCV and 3·3% (0·1–17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9–99·2) with Sii-PTCV and 0% (0·0–11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. Interpretation Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. Funding Serum Institute of India