scholarly journals Characterisation of factors contributing to the performance of nonwoven fibrous matrices as substrates for adenovirus vectored vaccine stabilisation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pawan Dulal ◽  
Robabeh Gharaei ◽  
Adam J. Berg ◽  
Adam A. Walters ◽  
Nicholas Hawkins ◽  
...  

AbstractAdenovirus vectors offer a platform technology for vaccine development. The value of the platform has been proven during the COVID-19 pandemic. Although good stability at 2–8 °C is an advantage of the platform, non-cold-chain distribution would have substantial advantages, in particular in low-income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving excellent recovery of adenovirus-vectored vaccines after storage at temperatures as high as 45 °C. This matrix is, however, prone to fragmentation and so not suitable for clinical translation. Here, we report an investigation of alternative fibrous matrices which might be suitable for clinical use. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components, finding that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to identify a potentially biocompatible matrix with encouraging performance. We discuss remaining challenges for transfer of the technology into clinical use, including reliability of process performance.

2020 ◽  
Author(s):  
Pawan Dulal ◽  
Adam A Walters ◽  
Nicholas Hawkins ◽  
Tim DW Claridge ◽  
Katarzyna Kowal ◽  
...  

AbstractThe global network of fridges and freezers known as the “cold chain” can account for a significant proportion of the total cost of vaccination and is susceptible to failure. Cost-efficient techniques to enhance stability of vaccines could prevent such losses and improve vaccination coverage, particularly in low income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving an excellent recovery of vaccines after storage at supraphysiological temperatures. This matrix is, however, prone to fragmentation and currently not suitable for clinical translation.Here, we report an investigation of alternative, potentially GMP compatible, fibrous matrices. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components. Our investigation shows that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to develop a custom-produced matrix with encouraging performance, as an initial step towards a biocompatible matrix for clinical translation. We discuss the path to transfer of the technology into clinical use, including potential obstacles.


Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 520
Author(s):  
Roberto Cárcamo-Calvo ◽  
Carlos Muñoz ◽  
Javier Buesa ◽  
Jesús Rodríguez-Díaz ◽  
Roberto Gozalbo-Rovira

Rotavirus is the leading cause of severe acute childhood gastroenteritis, responsible for more than 128,500 deaths per year, mainly in low-income countries. Although the mortality rate has dropped significantly since the introduction of the first vaccines around 2006, an estimated 83,158 deaths are still preventable. The two main vaccines currently deployed, Rotarix and RotaTeq, both live oral vaccines, have been shown to be less effective in developing countries. In addition, they have been associated with a slight risk of intussusception, and the need for cold chain maintenance limits the accessibility of these vaccines to certain areas, leaving 65% of children worldwide unvaccinated and therefore unprotected. Against this backdrop, here we review the main vaccines under development and the state of the art on potential alternatives.


2020 ◽  
Vol 46 (8) ◽  
pp. 499-501 ◽  
Author(s):  
Yangzi Liu ◽  
Sanjana Salwi ◽  
Brian C Drolet

The urgent drive for vaccine development in the midst of the current COVID-19 pandemic has prompted public and private organisations to invest heavily in research and development of a COVID-19 vaccine. Organisations globally have affirmed the commitment of fair global access, but the means by which a successful vaccine can be mass produced and equitably distributed remains notably unanswered. Barriers for low-income countries include the inability to afford vaccines as well as inadequate resources to vaccinate, barriers that are exacerbated during a pandemic. Fair distribution of a pandemic vaccine is unlikely without a solid ethical framework for allocation. This piece analyses four allocation paradigms: ability to develop or purchase; reciprocity; ability to implement; and distributive justice, and synthesises their ethical considerations to develop an allocation model to fit the COVID-19 pandemic.


Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1026
Author(s):  
Anna Hargrave ◽  
Abu Salim Mustafa ◽  
Asma Hanif ◽  
Javed H. Tunio ◽  
Shumaila Nida M. Hanif

HIV-1 infection and its progression to AIDS remains a significant global health challenge, particularly for low-income countries. Developing a vaccine to prevent HIV-1 infections has proven to be immensely challenging with complex biological acquisition and infection, unforeseen clinical trial disappointments, and funding issues. This paper discusses important landmarks of progress in HIV-1 vaccine development, various vaccine strategies, and clinical trials.


2017 ◽  
Vol 2 ◽  
pp. 70 ◽  
Author(s):  
Stephen B Gordon ◽  
Jamie Rylance ◽  
Amy Luck ◽  
Kondwani Jambo ◽  
Daniela M Ferreira ◽  
...  

Controlled human infection model (CHIM) studies have pivotal importance in vaccine development, being useful for proof of concept, pathogenesis, down-selection and immunogenicity studies.  To date, however, they have seldom been carried out in low and middle income countries (LMIC), which is where the greatest burden of vaccine preventable illness is found.  This workshop discussed the benefits and barriers to CHIM studies in Malawi.  Benefits include improved vaccine effectiveness and host country capacity development in clinical, laboratory and governance domains.  Barriers include acceptability, safety and regulatory issues. The report suggests a framework by which ethical, laboratory, scientific and governance issues may be addressed by investigators considering or planning CHIM in LMIC.


Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 63 ◽  
Author(s):  
Sheng-Qun Deng ◽  
Xian Yang ◽  
Yong Wei ◽  
Jia-Ting Chen ◽  
Xiao-Jun Wang ◽  
...  

Dengue virus (DENV) has become a global health threat with about half of the world’s population at risk of infection. Although the disease caused by DENV is self-limiting in the first infection, the antibody-dependent enhancement (ADE) effect increases the mortality in the second infection with a heterotypic virus. Since there is no specific efficient medicine in treatment, it is urgent to develop vaccines to prevent infection and disease progression. Currently, only a live attenuated vaccine, chimeric yellow fever 17D—tetravalent dengue vaccine (CYD-TDV), has been licensed for clinical use in some countries, and many candidate vaccines are still under research and development. This review discusses the progress, strengths, and weaknesses of the five types of vaccines including live attenuated vaccine, inactivated virus vaccine, recombinant subunit vaccine, viral vectored vaccine, and DNA vaccine.


Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 341 ◽  
Author(s):  
Olufemi Samuel Folorunso ◽  
Olihile M. Sebolai

Safety, efficacy, and cost-effectiveness are paramount to vaccine development. Following the isolation of rotavirus particles in 1969 and its evidence as an aetiology of severe dehydrating diarrhoea in infants and young children worldwide, the quest to find not only an acceptable and reliable but cost-effective vaccine has continued until now. Four live-attenuated oral rotavirus vaccines (LAORoVs) (Rotarix®, RotaTeq®, Rotavac®, and RotaSIIL®) have been developed and licensed to be used against all forms of rotavirus-associated infection. The efficacy of these vaccines is more obvious in the high-income countries (HIC) compared with the low- to middle-income countries (LMICs); however, the impact is far exceeding in the low-income countries (LICs). Despite the rotavirus vaccine efficacy and effectiveness, more than 90 countries (mostly Asia, America, and Europe) are yet to implement any of these vaccines. Implementation of these vaccines has continued to suffer a setback in these countries due to the vaccine cost, policy, discharging of strategic preventive measures, and infrastructures. This review reappraises the impacts and effectiveness of the current live-attenuated oral rotavirus vaccines from many representative countries of the globe. It examines the problems associated with the low efficacy of these vaccines and the way forward. Lastly, forefront efforts put forward to develop initial procedures for oral rotavirus vaccines were examined and re-connected to today vaccines.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255807
Author(s):  
Haydee Miranda-Ortiz ◽  
Edith A. Fernández-Figueroa ◽  
Erika B. Ruíz-García ◽  
Anallely Muñoz-Rivas ◽  
Alejandra Méndez-Pérez ◽  
...  

The use of saliva for the diagnosis of SARS-CoV-2 has shown to be a good alternative to nasopharyngeal swabs (NPS), since it permits self-collection, avoids the exposure of healthy persons to infected patients, reduces waiting times, eliminates the need of personal protective equipment and is non-invasive. Yet current saliva testing is still expensive due to the need of specialized tubes containing buffers to stabilize the RNA of SARS-CoV-2 and inactivate the virus. These tubes are expensive and not always accessible in sufficient quantities. We now developed an alternative saliva testing method, using TRIzol for extraction, viral inactivation, and storage of SARS-CoV-2 RNA, combined with RT-qPCR, which was comparable in its performance to NPS. Paired saliva samples and NPS were taken from 15 asymptomatic healthcare workers and one patient with SARS-CoV-2. Further 13 patients with SARS-CoV-2 were only saliva-tested. All the tests were performed according to CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. Saliva (4 mL) was taken in sterile 50 mL tubes, 1.5 mL TRIzol were added and mixed. Our results show that 5 μL of saliva RNA extracted with TRIzol allow for an adequate detection of the virus in patients positive for SARS-CoV-2 and was equally sensitive to NPS in TRIzol. We conclude that saliva testing using TRIzol is a recommendable method for diagnosis of SARS-CoV-2 since it has several advantages over currently used saliva tests: it can be done with normal sterile tubes, does not need cold-chain handling, is stable at room temperature, is non-invasive and less costly, making it more accessible for low-income countries. Cheaper saliva testing using TRIzol is especially relevant for low-income countries to optimize diagnosis and help define quarantine durations for families, healthcare workers, schools, and other public workplaces, thus decreasing infections and mortality caused by SARS-CoV-2.


2021 ◽  
Vol 2 (5) ◽  
pp. 408-411
Author(s):  
Diosey Ramon Lugo-Morin

The impact that the COVID-19 pandemic has had on global institutions and populations has been unprecedented. The health measures (e.g., confinement and social distancing) recommended by WHO and adopted by most nations in the world have not contained the spread of COVID-19. Vaccine development is expected to be a decisive element in controlling the pandemic, however, poor countries do not have immediate access to developed vaccines, which means that the COVID-19 pandemic will be present for some time among low-income countries. Against this daunting backdrop, it is necessary to explore more universal and inclusive ways of combating the COVID-19 pandemic and all future pandemics. Three conjectures are proposed that lead to a single path, unlocking the knowledge that cells have been able to accumulate over time. Although it may seem impossible in practice, the theory shows that knowledge exists to reach the frontiers of DNA.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S132-S133
Author(s):  
Dipendra Thapaliya ◽  
Samantha Mackey ◽  
Jhalka Kadariya ◽  
Bulgan Davaadash ◽  
Tara Smith

Abstract Background Streptococcus pyogenes is a significant cause of morbidity and mortality worldwide causing an estimated 1.8 million cases and 517,000 deaths each year. S. pyogenes infections disproportionately affect low-income countries where routine surveillance is not available. The objective of this study was to investigate the molecular epidemiology and antibiotic resistance of clinically relevant S. pyogenes isolates in Ulaanbaatar, Mongolia, to better understand the burden in this under-served population. Methods Clinical S. pyogenes isolates (n = 41) collected at the Bacteriological Reference Laboratory, National Center for Communicable Diseases, Ulaanbaatar, Mongolia, were cultured and characterized using PCR techniques. The emm gene was sequenced and emm type was assigned as per Centers for Disease Control and Prevention (CDC) methods and guideline. Multi-locus sequence typing (MLST) was carried out on selected isolates (n = 15). Antibiotic susceptibility testing (AST) was done via the Vitek-2 system as per manufacturer’s instructions. Results We observed 18 distinct emm types among the 41 S. pyogenes isolates. stG6792.0 was the most common emm type, accounting for more than one-third of the isolates (15/41) followed by emm2.0 (ST55) (5/41) and emm 82.0 (ST314) (2/41). A total of seven sequence types (STs) were detected among 15 tested isolates. The most common ST type was ST55 accounting for one-third of the isolates (5/15). Most of the isolates were susceptible to all tested drugs. Conclusion The findings of this study provided some insights regarding the molecular characteristics of S. pyogenes in Mongolia that will be crucial for future surveillance studies. Five isolates of this study had similar emm types (emm74.0, emm66.0, stG480.0, emm83.1, emm89.0) compared with a previous surveillance study. emm89.0 (ST101) was a major epidemiological isolate in the United States between 2000 and 2004. emm89.0 was also implicated with a recent single-clone outbreak in China. This information suggests the possibility of a shifting epidemiological trend of S. pyogenes on the global stage. The information about antibiotic susceptibility patterns and molecular types can help to devise better treatment strategies for S. pyogenes infections, and potentially inform vaccine development. Disclosures All authors: No reported disclosures.


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