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Protein content estimation of recombinant vaccines at drug product (DP) stage is a crucial lot release and stability indicating assay in biopharmaceutical industries. Regulatory bodies such as US-FDA and WHO necessitates the quantitation of protein content to assess process parameters as well as formulation losses. Estimation of protein content at DP stage in presence of adjuvants (e.g AlOOH, AlPO 4 , saponin and squalene) is quite challenging, and the challenge intensifies when the target protein is in Virus like particles (VLP) form, owing to its size and structural complexity. Methods available for protein estimation of adjuvanted vaccines mostly suffer from inaccuracy at lower protein concentrations and in most cases require antigen desorption before analysis. Present research work is based on the development of a rapid plate-based method for protein estimation through intrinsic fluorescence by using Malaria vaccine R21 VLP as a model protein. Present method exhibited linearity for protein estimation of R21, in the range of 5–30 µg/mL in Alhydrogel and 4–20 µg/mL for Matrix M adjuvant. The method was validated as per ICH guidelines. The limit of quantification was found to be 0.94 µg/mL for both Alhydrogel and Matrix M adjuvanted R21. The method was found specific, precise and repeatable. This method is superior in terms of less sample quantity requirement, multiple sample analysis, short turnaround time and is non-invasive. This method was found to be stability indicating, works for other proteins containing tryptophan residues and operates well even in presence of host cell proteins. Based on the study, present method can be used in vaccine industries for routine in-process sample analysis (both inline and offline), lot release of VLP based drug products in presence of Alhydrogel and saponin based adjuvant systems. [ABSTRACT FROM AUTHOR]

Adequate global vaccine coverage during an influenza pandemic is essential to mitigate morbidity, mortality, and economic impact. Vaccine development and production needs to be sufficient to meet a vast global demand, requiring international cooperation and local vaccine production capacity, especially in resource-constrained countries. The use of adjuvants is one approach to augment the number of available vaccine doses and to overcome potential vaccine shortages. Appropriately selected adjuvant technologies can decrease the amount of vaccine antigen required per dose, may broaden or lengthen the conferred protection against disease, and may even allow protective single-dose vaccination. Here we describe a technology transfer collaboration between Switzerland and Indonesia that led to the establishment of a vaccine formulation platform in Surabaya which involved the transfer of equipment and expertise to enable research and development of adjuvanted vaccine formulations and delivery systems. This new Indonesian capability aims to facilitate local and regional access to know-how relating to adjuvanted vaccine formulations, thus promoting their application to local vaccine developers. In this review, we aim to share the “lessons learned” from this project to both support and inspire future scientific collaborations of a similar nature.

Background: vaccination is the best approach to prevent influenza infections so far. Serological studies on the effect of different vaccine types are important to address vaccination campaigns and protect our population. In our study, we compared the serological response against influenza A subtypes using the non-adjuvanted influenza vaccine (NAIV) in adults and the elderly and the adjuvanted influenza vaccine (AIV) in the elderly. Methods: We performed a retrospective analysis by hemagglutination inhibition assay (HI) of serum samples right before and 28 days after seasonal influenza vaccination during the 1996–2017 seasons. Conclusions: The AIV presents better performance against the A(H3N2) subtype in the elderly whereas the NAIV induces a better response against A(H1N1)pdm09 in the same group.

In an attempt to understand the unique toxicity of adjuvanted vaccines, we studied how toxicity develops over time following vaccine administration. In addition to on- and off-target toxicity typically observed with general pharmaceuticals, we observed toxicity associated with both the generation and the broad action of effectors (antibodies and/or cytotoxic T lymphocytes, CTLs). The impact on effector generation appears to be related to local tolerance specific to the adjuvant. The vaccine immune response by effectors serves to demonstrate species relevance as outlined in the recent WHO guideline on the nonclinical evaluation of adjuvanted vaccines. When regarded as pharmaceuticals that function at sites of local administration, adjuvants have inherent on- and off-target toxicity. On-target toxicity of the adjuvant is typically associated with effector generation, and could vary depending on animal species. Therefore, the use of species with sensitivity to adjuvants described in the WHO guidelines is required to evaluate the toxicity of the vaccine associated with effector generation. Changes in safety pharmacology endpoints would be considered off-target and further studies are conducted only if changes in these endpoints are observed in nonclinical or clinical studies. Thus our decision tree does not recommend the routine conduct of stand-alone safety pharmacology studies. [ABSTRACT FROM AUTHOR]

Abstract: In this work, we evaluated the effect of the inclusion of different adjuvants in the vaccine formulation against Lactococcus garvieae in comparison with an aqueous bacterin. The aqueous and non mineral oil adjuvanted vaccines (Montanide-ISA-763-A and Aquamun) yielded a good protection 4 weeks after the immunization (RPS of 82.6, 84.8 and 86.9, respectively). The protective rates obtained for the adjuvants Montanide-IMS-2212 (water based nanoparticles with immunostimulant) and Carbomer (high molecular weight polymer organic of polyacrylic acid) were 45.7% and 56.5%, respectively. We also evaluated the duration of protection confered by Aquamun adjuvanted-vaccine in comparison with the aqueous bacterin. Three months after vaccination, the RPS values obtained with the aqueous vaccine was 40% whereas with the Aquamun adjuvanted-vaccine the protection increased to values of 92%. In addition, a long lasting protection was observed with this adjuvanted vaccine with RPS values of 90% and 83.3% in the challenges performed at 6 and 8 months post-vaccination, respectively. [Copyright &y& Elsevier]

Adequate global vaccine coverage during an influenza pandemic is essential to mitigate morbidity, mortality, and economic impact. Vaccine development and production needs to be sufficient to meet a vast global demand, requiring international cooperation and local vaccine production capacity, especially in resource-constrained countries. The use of adjuvants is one approach to augment the number of available vaccine doses and to overcome potential vaccine shortages. Appropriately selected adjuvant technologies can decrease the amount of vaccine antigen required per dose, may broaden or lengthen the conferred protection against disease, and may even allow protective single-dose vaccination. Here we describe a technology transfer collaboration between Switzerland and Indonesia that led to the establishment of a vaccine formulation platform in Surabaya which involved the transfer of equipment and expertise to enable research and development of adjuvanted vaccine formulations and delivery systems. This new Indonesian capability aims to facilitate local and regional access to know-how relating to adjuvanted vaccine formulations, thus promoting their application to local vaccine developers. In this review, we aim to share the "lessons learned" from this project to both support and inspire future scientific collaborations of a similar nature. [ABSTRACT FROM AUTHOR]

Background: vaccination is the best approach to prevent influenza infections so far. Serological studies on the effect of different vaccine types are important to address vaccination campaigns and protect our population. In our study, we compared the serological response against influenza A subtypes using the non-adjuvanted influenza vaccine (NAIV) in adults and the elderly and the adjuvanted influenza vaccine (AIV) in the elderly. Methods: We performed a retrospective analysis by hemagglutination inhibition assay (HI) of serum samples right before and 28 days after seasonal influenza vaccination during the 1996–2017 seasons. Conclusions: The AIV presents better performance against the A(H3N2) subtype in the elderly whereas the NAIV induces a better response against A(H1N1)pdm09 in the same group. [ABSTRACT FROM AUTHOR]

Background: Despite a long-standing vaccination programme, seasonal influenza remains a major public health problem in England, in particular for the elderly where a significant disease burden remains despite vaccine coverage approaching the WHO target of 75%. The recently licensed adjuvanted trivalent vaccines (TIV-ADJ) have been shown to offer greater protection for the elderly compared to the standard-dose non-adjuvanted trivalent vaccines (TIV), particularly for those individuals 75 years old and above for whom the TIV has limited effectiveness. We assessed the cost-effectiveness of the TIV-ADJ for use in the elderly., Methods: We used a dynamic SEIR-type transmission model coupled with an economic evaluation framework, estimating the reduction in GP consultations, hospitalisations and influenza-attributable mortality. We assessed the optimal use of the TIV-ADJ by estimating the cost-effectiveness of programmes that used this vaccine in the 65+ and 75+ age groups., Findings: The use of TIV-ADJ is highly cost-effective for both target age cohorts with incremental cost-effectiveness ratios well below the £20,000 per quality-adjusted life year (QALY) with over 90% probability that the vaccine is cost-effective at a cost-effectiveness threshold of £30,000 per QALY., Interpretation: The increased protection provided across all three influenza vaccine sub-types makes TIV-ADJ a more attractive option than TIV from the perspective of the healthcare provider, driven by the increased efficacy against A(H3N2). When deciding on the optimal use of the newly available vaccine it is important to consider the fact that TIV has very limited effectiveness for the 75+ age group, who would therefore get the greatest benefit from a more effective vaccine., Funding: I-MOVE+ project (Integrated Monitoring of Vaccines in Europe) through the European Union's Horizon 2020 research and innovation programme under grant agreement #634446 and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections at Imperial College London in partnership with Public Health England, as well as the NIHR HPRU in Immunisation at the London School of Hygiene and Tropical Medicine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Annual vaccination is the main mean of preventing influenza in the elderly. In order to evaluate the effectiveness of the adjuvanted seasonal influenza vaccines available in Italy in preventing hospitalization for influenza and pneumonia, a matched case-control study was performed in elderly subjects during the 2010-2011 season in Genoa (Italy). Cases and controls were matched in a 1:1 ratio according to gender, age, socio-economic status and type of influenza vaccine. Vaccine effectiveness was calculated as IVE = [(1-OR)x100] and crude odds ratios were estimated through conditional logistic regression models. Adjusted odds ratios were estimated through multivariable logistic models.   In the study area, influenza activity was moderate in the 2010-2011 season, with optimal matching between circulating viruses and vaccine strains. We recruited 187 case-control pairs; 46.5% of cases and 79.1% of controls had been vaccinated. The adjuvanted influenza vaccines (Fluad (®) considered together with Inflexal V (®) ) were associated with a significant reduction in the risk of hospitalization, their effectiveness being 94.8% (CI 77.1-98.8). Adjusted vaccine effectiveness was 95.2% (CI 62.8-99.4) and 87.8 (CI 0.0-98.9) for Inflexal V (®) and Fluad (®) , respectively. Both adjuvanted vaccines proved effective, although the results displayed statistical significance only for Inflexal V (®) (p = 0.004), while for Fluad (®) statistical significance was not reached (p = 0.09). Our study is the first to provide information on the effectiveness of Inflexal V (®) in terms of reducing hospitalizations for influenza or pneumonia in the elderly, and demonstrates that this vaccine yields a high degree of protection and that its use would generate considerable saving for the National Health Service.