Bovine rotavirus pentavalent vaccine development in India

AbstractA 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

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

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

Introduction: 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. Areas covered: In this review, we have described the detailed manufacturing process of Rabivax-S and summary of preclinical and clinical development based on the data generated in-house. Expert commentary: Rabivax-S has been developed on Vero ATCC CCL81 cells using Pitman Moore (PM3218) strain. Following all the GMP requirements the vaccine was tested in GLP toxicology studies. Further it underwent clinical trials in preexposure and postexposure settings and was found safe and immunogenic

Safety and Immunogenicity of Dry Powder Measles Vaccine Administered by Inhalation: A Randomized Controlled Phase I Clinical Trial

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 vaccinethat 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 vaccinein 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 inthis controlled Phase I clinical study. Subjects were randomly assigned in 1:1:1 ratio to receive eitherMVDP by Puffhaler®or by SoloventTMdevices or the licensed subcutaneous measles vaccine. Adverseevents (AEs) were recorded with diary cards until day 28 post-vaccination and subjects were followedfor 180 days post-vaccination to assess potential serious long term adverse events. Measles antibodywas measured 7 days before vaccination and at days 21 and 77 after vaccination by ELISA and a plaquereduction neutralization test.Results: All subjects completed the study according to protocol. Most subjects had high levels of base-line measles antibody. No adverse events were reported. MVDP produced serologic responses similar tosubcutaneous vaccination.Conclusions: MVDP was well tolerated in all subjects. Most subjects had high baseline measles antibodytiter which limited ability to measure the serologic responses, and may have limited the adverse eventsfollowing vaccination. Additional studies in subjects without pre-existing measles antibody are neededto further elucidate the safety and immunogenicity of MVDP

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. Live attenuated vaccines, unlike inactivated or viral-protein-based vaccines, offer broader immune engagement. Given effectiveness of live attenuated vaccines in controlling infectious diseases such as mumps, measles and rubella, we undertook development of a live attenuated COVID-19 vaccine with an aim to vaccinate children beyond 6 months of age. An attenuated vaccine candidate (dCoV), engineered to express sub-optimal codons and deleted polybasic furin cleavage sites in the spike protein of the SARS-CoV-2 WA/1 strain, was developed and tested in hamsters. Hamsters immunized with dCoV via intranasal or intramuscular routes induced high levels of neutralizing antibodies and exhibited complete protection against the SARS-CoV-2 wild-type isolates, i.e., the Wuhan-like (USA-WA1/2020) and Delta variants (B.1.617.2) in a challenge study. In addition, the dCoV formulated with the marketed measles–rubella (MR) vaccine, designated as MR-dCoV, administered to hamsters via intramuscular route, also protected against both SARS-CoV-2 challenges, and dCoV did not interfere with the MR vaccine-mediated immune response. The safety and efficacy of the dCoV and the MR-dCoV against both variants of SARS-CoV-2 opens the possibility of early immunization in children without an additional injection

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. Live attenuated vaccines, unlike inactivated or viral-protein-based vaccines, offer broader immune engagement. Given effectiveness of live attenuated vaccines in controlling infectious diseases such as mumps, measles and rubella, we undertook development of a live attenuated COVID-19 vaccine with an aim to vaccinate children beyond 6 months of age. An attenuated vaccine candidate (dCoV), engineered to express sub-optimal codons and deleted polybasic furin cleavage sites in the spike protein of the SARS-CoV-2 WA/1 strain, was developed and tested in hamsters. Hamsters immunized with dCoV via intranasal or intramuscular routes induced high levels of neutralizing antibodies and exhibited complete protection against the SARS-CoV-2 wild-type isolates, i.e., the Wuhan-like (USA-WA1/2020) and Delta variants (B.1.617.2) in a challenge study. In addition, the dCoV formulated with the marketed measles–rubella (MR) vaccine, designated as MR-dCoV, administered to hamsters via intramuscular route, also protected against both SARS-CoV-2 challenges, and dCoV did not interfere with the MR vaccine-mediated immune response. The safety and efficacy of the dCoV and the MR-dCoV against both variants of SARS-CoV-2 opens the possibility of early immunization in children without an additional injection