Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine versus a quadrivalent meningococcal conjugate vaccine in adults in India: an observer-blind, randomised, active-controlled, phase 2/3 study.

Background: Meningococcal disease remains an important public health problem globally. We assessed the non-inferiority and the lot-to-lot consistency of a pentavalent meningococcal ACYWX conjugate vaccine (NmCV-5; Serum Institute of India, Pune, India) versus a quadrivalent meningococcal ACWY conjugate vaccine (MenACWY-D) in healthy adults.

Methods: In this observer-blind, randomised, active-controlled, phase 2/3 study, healthy adults aged 18-85 years were recruited from nine hospitals across seven cities in India.

An observer-blind, randomised, placebo-controlled, phase 1, single ascending dose study of dengue monoclonal antibody in healthy adults in Australia.

Background: Dengue is highly prevalent in Asia and Latin America and has no specific dengue antiviral treatment. A recombinant monoclonal antibody (VIS513) that neutralises all four serotypes of the dengue virus has been developed in India. After confirmation of safety and efficacy in preclinical studies, it was tested in a first-in-human study to assess the safety and pharmacokinetics.

Acid hydrolysis conditions for quantification of meningococcal X polysaccharide in a pentavalent vaccine using HPAEC-PAD/ESI-MS.

A selective and sensitive method was evaluated for quantitation of meningococcal X (Men X) polysaccharide in pentavalent meningococcal A, C, W, Y and X conjugate vaccine using different acid hydrolysis conditions like HCl, TFA, HF, HF-TFA, and HF-HCl. High-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) using CarboPac PA10 column was used to identify the hydrolyzed products based on retention time and its comparison with monosaccharide standards. Complete release of glucosamine (GlcN) from Men X in monovalent bulk and pentavalent vaccine samples was achieved using HF hydrolysis at 80 °C for 2 h.

Effect of trifluoroacetic acid on the antigenicity of capsular polysaccharides obtained from various Streptococcus pneumoniae serotypes.

Determining the safety, antigenicity, and immunogenicity by in vitro and in vivo studies is a prerequisite for the development of new vaccines. And this study investigated it for a vaccine made from Streptococcus pneumoniae serotypes 2, 5, 12F, 18C, and 22F. The crude CPS was purified and partially depolymerized by conventional and trifluoroacetic acid methods.

A Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and immunogenicity of a tetravalent live attenuated dengue vaccine in adults.

Background: Dengue fever is an important public health problem, especially in Asia and South America. A tetravalent live attenuated dengue vaccine was manufactured in India after receipt of vaccine strains from NIAID, NIH, USA.

Methods: This was a Phase 1, double-blind, randomized, placebo-controlled study performed in 60 healthy adults of 18 to 45 years.

Evaluation of structural modification induced activation of pneumococcal polysaccharide by GC-MS for the conjugate vaccine.

Polysaccharide (Ps) activation evaluation is an imperative quality attribute in a conjugate vaccine. Pneumococcal polysaccharide (PnPs) serotypes 5, 6B, 14, 19A and 23F were cyanylated for 3 and 8 min. The cyanylated and non-cyanylated polysaccharides were methanolysed and derivatized to assess the activation of each sugar by GC-MS.

A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters.

Children are at risk of infection from severe acute respiratory syndrome coronavirus-2 virus (SARS-CoV-2) resulting in coronavirus disease (COVID-19) and its more severe forms. New-born infants are expected to receive short-term protection from passively transferred maternal antibodies from their mothers who are immunized with first-generation COVID-19 vaccines. Passively transferred antibodies are expected to wane within first 6 months of infant's life, leaving them vulnerable to COVID-19.

Quantitation of free cyanide using ion exchange chromatography in Neisseria meningitidis serogroups A, C, W, Y and X conjugates used in vaccine manufacture.

Polysaccharide vaccines essentially used in the prevention of bacterial infections are known to be good immunogens when conjugated to an immunogenic protein using various cyanylating agents. Analysis of residual cyanide in polysaccharide conjugate vaccines is an ardent task due to the complexity of the sample matrices and the lack of suitable methods. We report a selective ion chromatography method with electrochemical detection using IonPac AS7 column for estimation of residual cyanide in meningococcal serogroups A, C, W, Y and X bulk conjugates in presence of other interfering ions.

Purification of capsular polysaccharides isolated from S. pneumoniae serotype 2 by hydrogen peroxide and endonuclease.

A high-quality and cost-effective purification procedure is one of the most important requirements for manufacturing glycoconjugate vaccines. The goal of the present work was to devise a method for removing impurities such as protein and nucleic acid from Streptococcus pneumoniae serotype 2 capsular polysaccharides (CPS). The use of hydrogen peroxide for the reduction of impurities of crude CPS was investigated.

Partial depolymerization of capsular polysaccharides isolated from Streptococcus pneumoniae serotype 2 by various methods.

Partial depolymerization of bacterial capsular polysaccharides (CPS) is an essential process carried out before its use as an antigenic preparation in a vaccine industry. Choice of CPS depolymerization methods depends on the process robustness, reproducibility, yield, retention of CPS bioactivity, etc. Partial depolymerization methods based on chemicals, enzymes, mechanical, thermal, etc.

Quantitation of endotoxin by gas chromatography-mass spectrometry in Neisseria meningitidis serogroups A, C, W, Y and X during polysaccharide purification used in conjugate vaccine.

Bacterial lipopolysaccharide (LPS) responsible for endotoxin effect induces inflammatory reactions. The endotoxins are difficult to separate from the gram-negative polysaccharide (PS) during polysaccharide purification. The most common method to quantify LPS is the limulus amebocyte lysate (LAL) test which interferes with the agents used during PS purification.

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 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 (rCRM), 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.

Meningococcal Serogroup ACWYX Conjugate Vaccine in Malian Toddlers.

Background: serogroups A, B, C, W, X, and Y cause outbreaks of meningococcal disease. Quadrivalent conjugate vaccines targeting the A, C, W, and Y serogroups are available. A pentavalent vaccine that also includes serogroup X (NmCV-5) is under development.

Simultaneous purification and depolymerization of Streptococcus pneumoniae serotype 2 capsular polysaccharides by trifluoroacetic acid.

Development of an effective purification process in order to provide low cost and high-quality vaccine is the necessity of glycoconjugate vaccine manufacturing industries. In the present study, we have attempted to develop a method for simultaneous purification and depolymerization process for capsular polysaccharides (CPS) derived from Streptococcus pneumoniae serotype 2. Trifluoroacetic acid (TFA) was used to precipitate impurities which were then removed by centrifugation.

Development of competitive inhibition ELISA as an effective potency test to analyze human rabies vaccines and assessment of the antigenic epitope of rabies glycoprotein.

The potency of all modern tissue culture human rabies vaccines is measured based on the National Institute of Health (NIH) potency test that is laborious, time-consuming, involves large test variations and requires sacrifice of large number of animals. To circumvent these limitations, several researchers and WHO expert working groups have discussed development of alternative in vitro methods to replace the NIH potency test. Although several immunochemical methods have been proposed to quantify rabies glycoprotein (G-protein) using multiple murine monoclonal antibodies, we report an In vitro competitive inhibition ELISA (CIA) method based on the use of a neutralizing rabies glycoprotein site III directed novel therapeutic human rabies monoclonal antibody (RAB1) that shows equivalence to the mice NIH potency test in recognition of neutralization site of the glycoprotein.

Immunogenicity and efficacy comparison of MDCK cell-based and egg-based live attenuated influenza vaccines of H5 and H7 subtypes in ferrets.

During a pandemic, the availability of specific pathogen free chicken eggs is a major bottleneck for up-scaling response to the demand for influenza vaccine. This has led us to explore the use of Madin-Darby Canine Kidney (MDCK) cells for the manufacture of live attenuated influenza vaccine (LAIV) that provides production flexibility and speed. The present study reports the comparison of the immunogenicity and efficacy of two MDCK-based LAIVs against two egg-based LAIVs prepared from the same pandemic potential strains of H5 and H7 subtypes after a single dose of the vaccine followed by a challenge with a homologous wild type strain.

Evaluation of a sensitive GC-MS method to detect polysorbate 80 in vaccine preparation.

Polysorbates are the most versatile and common surfactants used as protein stabilizers. Analysis of residual polysorbate 80 (PS 80) in conjugate vaccine is challenging due to complexity of conjugate matrices and heterogeneity of the structure of the PS 80 analyte. The direct approach using high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) and gas chromatography-mass spectrometry (GC-MS) that is based on oleic acid methyl ester formation followed by transesterification have been evaluated to quantitate residual PS 80 in meningococcal serogroups A, C, W, Y and X bulk conjugates.

Quantitation of residual sodium dodecyl sulfate in meningococcal polysaccharide by gas chromatography-mass spectrometry.

Sodium dodecyl sulfate (SDS) is a commonly used surfactant in protein solubilization and also during the polysaccharide purification. A GC-MS method has been developed to quantitate residual SDS in meningococcal polysaccharide serogroups A,C,W,Y and X circumventing the need of spectroscopic assays and HPLC based methods which are either unstable or requires the confirmation by MS. The developed method is based on quantitative conversion of SDS to 1-dodecanol at elevated temperature.

Lack of immune interference between inactivated polio vaccine and inactivated rotavirus vaccine co-administered by intramuscular injection in two animal species.

A parenteral inactivated rotavirus vaccine (IRV) in development could address three problems with current live oral rotavirus vaccines (ORV): their lower efficacy in low and middle-income countries (LMICs), lingering concerns about their association with intussusception, and their requirement for a separate supply chain with large volume cold storage. Adding a new parenteral IRV to the current schedule of childhood immunizations would be more acceptable if it could be combined with another injectable vaccine such as inactivated polio vaccine (IPV). Current plans for polio eradication call for phasing out oral polio vaccine (OPV) and transitioning to IPV, initially in LMICs as a single dose booster after two doses of OPV and ultimately as a two dose schedule.

Immunogenicity and efficacy of the monovalent, trivalent and quadrivalent intranasal live attenuated influenza vaccines containing different pdmH1N1 strains.

A ferret challenge study was conducted to address the efficacy of the egg-based and Madin-Darby canine kidney (MDCK)-based live attenuated influenza vaccine (LAIV) strains. Vaccines derived as 6:2 reassortants from the A/Leningrad/134/17/57 master donor strain and the HA and NA components from the A/California/07/2009 (A/Cal)- and A/Michigan/45/2015 (A/Mich)-like strains of type A H1N1 influenza virus were used in the study. Monovalent, trivalent and quadrivalent formulations of the LAIV containing either of the two H1N1 strains were analysed.

Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine containing serogroups A, C, Y, W, and X in healthy adults: a phase 1, single-centre, double-blind, randomised, controlled study.

Background: Invasive meningococcal disease is an important public health problem, especially in sub-Saharan Africa. After introduction of MenAfriVac in 2010, Neisseria meningitidis serogroup A disease has been almost eliminated from the region. However, serogroups C, W, Y, and X continue to cause disease outbreaks.

A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants.

Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14weeks of age along with routine vaccines.

Stability of heat stable, live attenuated Rotavirus vaccine (ROTASIIL®).

Vaccines currently available across the globe are stored and transported in a continuous cold-chain at 2-8°C or below -20°C. A temperature excursion outside this range affects the potency of the vaccines. Such vaccines need to be discarded leading wastage.

Development of a new purified vero cell rabies vaccine (Rabivax-S) at the serum institute of India Pvt Ltd.

Rabies is a 100% fatal disease with significant disease burden in Asia and Africa but preventable with vaccines and immunoglobulins. There are very few WHO prequalified cell culture derived rabies vaccines available globally for use in humans. We have developed a new purified vero cell rabies vaccine (Rabivax-S) to meet this demand.

A randomized non-inferiority clinical study to assess post-exposure prophylaxis by a new purified vero cell rabies vaccine (Rabivax-S) administered by intramuscular and intradermal routes.

Background: Rabies is a 100% fatal disease but preventable with vaccines and immunoglobulins. We have developed a new purified vero cell rabies vaccine (Rabivax-S) and evaluated its safety and immunogenicity in post-exposure prophylaxis by intramuscular (IM) and intradermal (ID) routes.

Methods: This was a randomized active-controlled non-inferiority study in 180 individuals (age 5years and above) with suspected rabies exposure (90 each with WHO Category II and Category III exposures).