Brazilian meningococcal C conjugate vaccine: Scaling up studies

Bastos, Renata Chagas; Souza, Iaralice Medeiros de; Silva, Milton Neto da; Silva, Flavia de Paiva; Figueira, Elza Scott; Leal, Maria de Lurdes; Jessouroun, Ellen; Silva, José Godinho da; Medronho, Ricardo de Andrade; Silveira, Ivna Alana Freitas Brasileiro da

doi:10.1016/j.vaccine.2015.03.097

Cited by 7 publications

(8 citation statements)

References 25 publications

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“…The R&D phase involves a small-scale investigation into the feasibility of the vaccine design and formulation to establish the efficacy and safety of the vaccine in laboratory studies. In contrast, the process optimization and scale-up phase is defined as “the consolidation of a large-scale process based on results obtained from experiments with small-scale equipment” (Bastos et al 2015 ). This phase involves determination of the optimal bioprocess parameters for efficient large-scale vaccine production while maintaining product quality, safety and stability.…”

Section: Introductionmentioning

confidence: 99%

“…Like any new product manufacturing system, commercial vaccine production must be scalable for large-scale production and supply to meet global demand (Smith et al 2011 ). However, the greatest hurdle for commercial vaccine manufacturers to overcome is the challenge of realizing an industrial vaccine product that elicits an immunological response similar to that observed during the smaller laboratory scale study (Bastos et al 2015 ). Notably, small-scale preparation of biologics and vaccines in the laboratory is typically achieved in smaller quantities in a micro-environment with controlled parameters (Bastos et al 2015 ; Damle et al 2020 ; Garcia-Ochoa and Gomez 2009 ; Kanesa-thasan et al 2011 ; Smith et al 2011 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, the greatest hurdle for commercial vaccine manufacturers to overcome is the challenge of realizing an industrial vaccine product that elicits an immunological response similar to that observed during the smaller laboratory scale study (Bastos et al 2015 ). Notably, small-scale preparation of biologics and vaccines in the laboratory is typically achieved in smaller quantities in a micro-environment with controlled parameters (Bastos et al 2015 ; Damle et al 2020 ; Garcia-Ochoa and Gomez 2009 ; Kanesa-thasan et al 2011 ; Smith et al 2011 ). In contrast, industrial-scale production of biologics is typically conducted in large equipment (a macro-environment), which typically offers less control over batch homogeneity (Wang et al 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study

Lyu,

Zhao,

Zuo

et al. 2024

Appl Microbiol Biotechnol

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Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13–17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. Key points • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study

Lyu,

Zhao,

Zuo

et al. 2024

Appl Microbiol Biotechnol

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“…Despite advances in the diagnosis and treatment of infectious diseases, invasive meningococcal disease (IMD) is still a major public health concern (Cordeiro et al, 2007;Agrawal and Nadel, 2011;Sáfadi et al, 2012). In Brazil, meningococcal infection is endemic and presents in a cyclical pattern, with most cases occurring during the winter, interspersed with occasional outbreaks (Souza and Seguro, 2008;Sáfadi et al, 2012;Bastos et al, 2015). The disease still carries high case fatality rates (CFR) and the risk of serious sequelae.…”

Section: Introductionmentioning

confidence: 99%

“…The disease still carries high case fatality rates (CFR) and the risk of serious sequelae. In this context, vaccination is considered the best strategy for prevention and control (Bastos et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Epidemiological burden of meningococcal disease in Brazil: A systematic literature review and database analysis

Almeida¹,

Spinardi²,

Cané³

2019

International Journal of Infectious Diseases

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The aim of this study was to evaluate the epidemiological profile of invasive meningococcal disease (IMD) in Brazil, the first Latin American country to introduce the group C meningococcal conjugate vaccine (included in the vaccination schedule in 2010). Methods: A systematic review was conducted, covering the years 2005-2017, to identify epidemiological information on IMD and Neisseria meningitidis carriers in Brazil. Documents from the Brazilian Ministry of Health and two public databases were analyzed to determine annual incidence rates, absolute numbers of diagnosed cases, serogroups identified, the relative distribution of cases per serogroup, and the case fatality rate (CFR). Results: Sixteen studies were selected. The incidence rate ranged from 0.88 to 5.3 cases per 100 000 inhabitants per year. According to secondary data, the annual incidence of IMD in 2015 was highest in males <1 year old (7.1/100 000). The number of diagnosed cases declined significantly over the years. In the literature, IMD showed a CFR from 20.0% to 50.0%, and a higher CFR for serogroup W (17.8%). Secondary data showed an absolute reduction in meningitis-attributable deaths between 2007 and 2015; however, the CFR remained stable (11.1% in 2007 and 8.4% in 2015). In 2015, serogroup W showed the highest CFR (24.1%), followed by serogroups C (19.2%), B (17.7%), and Y (14.3%). Conclusions: Despite a reduction in cases, the CFR remained stable and similar in the different age groups, even for disease caused by different serogroups. The highest CFR was found to be associated with serogroup W.

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Brazilian meningococcal C conjugate vaccine: physicochemical, immunological, and thermal stability characteristics

et al. 2017

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High temperature is known to cause some instability in polysaccharide-protein conjugated vaccines and studies under stress conditions may be useful in determining whether short-term accidental exposure to undesired conditions can compromise product quality. In this study, we examined the structural stability of three industrial batches of Brazilian Meningococcal C conjugate bulk (MPCT) incubated at 4, 37, and 55 °C for 5 weeks. The effect of exposure to the storage temperatures was monitored by HPLC-SEC, CZE, CD and NMR techniques. The immunological significance of any physicochemical changes observed in MPCT was determined by SBA and ELISA assays of serum from immunized mice. Fluorescence emission spectra at 4 and 37 °C were similar among all samples and compatible with the native fold of the carrier protein. Fluorescence spectra of MPCT stored at 55 °C decreased in intensity and had a significant red-shift, indicating conformational changes. Far-UV CD spectra revealed a trend toward loss of structural conformation as storage temperature was increased to 55 °C. The NMR data showed modified signal intensity of the aromatic and aliphatic residues, mainly for samples incubated at 55 °C, suggesting a partial loss of tertiary structure. About 50% free saccharide content was found in bulks stored at 55 °C, but no difference was observed in the IgG or SBA titers. The present study showed physicochemical methods alone are insufficient to predict the biological activity of a MPCT conjugate vaccine without extensive validation against immunological data. However, they provide a sensitive means of detecting changes induced in a vaccine exposed to adverse environmental condition.

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Brazilian meningococcal C conjugate vaccine: Scaling up studies

Cited by 7 publications

References 25 publications

Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study

Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study

Epidemiological burden of meningococcal disease in Brazil: A systematic literature review and database analysis

Brazilian meningococcal C conjugate vaccine: physicochemical, immunological, and thermal stability characteristics

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