scholarly journals Mice immunized with the vaccine candidate HexaPro spike produce neutralizing antibodies against SARS-CoV-2

2021 ◽  
Author(s):  
Chotiwat Seephetdee ◽  
Nattawut Buasri ◽  
Kanit Bhukhai ◽  
Kitima Srisanga ◽  
Suwimon Manopwisedjaroen ◽  
...  

Updated and revised versions of COVID-19 vaccines are vital due to genetic variations of the SARS-CoV-2 spike antigen. Furthermore, vaccines that are safe, cost-effective, and logistically friendly are critically needed for global equity, especially for middle to low income countries. Recombinant protein-based subunit vaccines against SARS-CoV-2 have been reported with the use of the receptor binding domain (RBD) and the prefusion spike trimers (S-2P). Recently, a new version of prefusion spike trimers, so called "HexaPro", has been shown for its physical property to possess two RBD in the "up" conformation, as opposed to just one exposed RBD found in S-2P. Importantly, this HexaPro spike antigen is more stable than S-2P, raising its feasibility for global logistics and supply chain. Here, we report that the spike protein HexaPro offers a promising candidate for SARS-CoV-2 vaccine. Mice immunized by the recombinant HexaPro adjuvanted with aluminium hydroxide using a prime-boost regimen produced high-titer neutralizing antibodies for up to 56 days after initial immunization against live SARS-CoV-2 infection. In addition, the level of neutralization activity is comparable to that of convalescence sera. Our results indicate that the HexaPro subunit vaccine confers neutralization activity in sera collected from mice receiving the prime-boost regimen.

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 498
Author(s):  
Chotiwat Seephetdee ◽  
Nattawut Buasri ◽  
Kanit Bhukhai ◽  
Kitima Srisanga ◽  
Suwimon Manopwisedjaroen ◽  
...  

Updated and revised versions of COVID-19 vaccines are vital due to genetic variations of the SARS-CoV-2 spike antigen. Furthermore, vaccines that are safe, cost-effective, and logistic-friendly are critically needed for global equity, especially for middle- to low-income countries. Recombinant protein-based subunit vaccines against SARS-CoV-2 have been reported using the receptor-binding domain (RBD) and the prefusion spike trimers (S-2P). Recently, a new version of prefusion spike trimers, named HexaPro, has been shown to possess two RBD in the “up” conformation, due to its physical property, as opposed to just one exposed RBD found in S-2P. Importantly, this HexaPro spike antigen is more stable than S-2P, raising its feasibility for global logistics and supply chain. Here, we report that the spike protein HexaPro offers a promising candidate for the SARS-CoV-2 vaccine. Mice immunized by the recombinant HexaPro adjuvanted with aluminum hydroxide using a prime-boost regimen produced high-titer neutralizing antibodies for up to 56 days after initial immunization against live SARS-CoV-2 infection. Also, the level of neutralization activity is comparable to that of convalescence sera. Our results indicate that the HexaPro subunit vaccine confers neutralization activity in sera collected from mice receiving the prime-boost regimen.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1352
Author(s):  
Darius Riziki Martin ◽  
Nicole Remaliah Sibuyi ◽  
Phumuzile Dube ◽  
Adewale Oluwaseun Fadaka ◽  
Ruben Cloete ◽  
...  

The transmission of Tuberculosis (TB) is very rapid and the burden it places on health care systems is felt globally. The effective management and prevention of this disease requires that it is detected early. Current TB diagnostic approaches, such as the culture, sputum smear, skin tuberculin, and molecular tests are time-consuming, and some are unaffordable for low-income countries. Rapid tests for disease biomarker detection are mostly based on immunological assays that use antibodies which are costly to produce, have low sensitivity and stability. Aptamers can replace antibodies in these diagnostic tests for the development of new rapid tests that are more cost effective; more stable at high temperatures and therefore have a better shelf life; do not have batch-to-batch variations, and thus more consistently bind to a specific target with similar or higher specificity and selectivity and are therefore more reliable. Advancements in TB research, in particular the application of proteomics to identify TB specific biomarkers, led to the identification of a number of biomarker proteins, that can be used to develop aptamer-based diagnostic assays able to screen individuals at the point-of-care (POC) more efficiently in resource-limited settings.


Author(s):  
S Wang ◽  
RT Muir ◽  
BC Warf

Background: Pediatric hydrocephalus is one of the most common neurosurgical conditions and is a major contributor to the global burden of surgically treatable diseases. Methods: The authors conducted a literature review around the topic of pediatric hydrocephalus in the context of global surgery, the unique challenges to creating access to care in low-income countries, and current international efforts to address the problem. Results: Developing countries face the greatest burden of pediatric hydrocephalus due to high birth rates and greater risk of neonatal infections. This burden is related to more general global health challenges, including malnutrition, infectious diseases, maternal and perinatal risk factors, and education gaps. Unique challenges pertaining to the treatment of hydrocephalus in the developing world include a preponderance of postinfectious hydrocephalus, limited resources, and restricted access to neurosurgical care. In the 21st century, several organizations have established programs that provide hydrocephalus treatment and neurosurgical training in Africa, Central and South America, Haiti, and Southeast Asia. These international efforts have employed various models to achieve the goals of providing safe, sustainable, and cost-effective treatment. Conclusions: Broader commitment from the pediatric neurosurgery community, increased funding, public education, surgeon training, and ongoing surgical innovation will be needed to meaningfully address the global burden of untreated hydrocephalus.


2020 ◽  
Author(s):  
Thibault Colombani ◽  
Loek Eggermont ◽  
Zachary Rogers ◽  
Lindsay McKay ◽  
Laura Avena ◽  
...  

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global health crisis, resulting in a critical need for effective vaccines that generate protective antibodies. Protein subunit vaccines represent a promising approach but often lack the immunogenicity required for strong immune stimulation. To overcome this challenge, we first demonstrate that advanced biomaterials boost effectiveness of SARS-CoV-2 protein subunit vaccines. Additionally, we report that oxygen is a powerful immunological co-adjuvant, a game-changer in the field for unlocking the full potential of vaccines. Mice immunized with oxygen-generating cryogel vaccines exhibited a robust and balanced Th1 and Th2 immune response, leading to sustained and high titer production of neutralizing antibodies against SARS-CoV-2. Our data indicate that this platform is a revolutionary technology with the potential to reinforce any vaccine.


2019 ◽  
Vol 14 (5) ◽  
pp. 457-459 ◽  
Author(s):  
Frederike van Wijck ◽  
Julie Bernhardt ◽  
Sandra A Billinger ◽  
Marie-Louise Bird ◽  
Janice Eng ◽  
...  

There is an urgent need to improve life after stroke across the world—especially in low-income countries—through methods that are effective, equitable and sustainable. This paper highlights physical activity (PA) as a prime candidate for implementation. PA reduces modifiable risk factors for first and recurrent stroke and improves function and activity during rehabilitation and following discharge. Preliminary evidence also indicates PA is cost-effective. This compelling evidence urgently needs to be translated into seamless pathways to enable stroke survivors across the world to engage in a more active lifestyle. Although more quality research is needed—particularly on how to optimize uptake and maintenance of PA—this should not delay implementation of high-quality evidence already available. This paper shares examples of best practice service models from low-, middle-, and high-income countries around the world. The authors call for a concerted effort to implement high-quality PA services to improve life after stroke for all.


2006 ◽  
Vol 32 (2-3) ◽  
pp. 159-173 ◽  
Author(s):  
Kevin Outterson

The World Health Organization’s CHOICE program analyzes the cost effectiveness of various health interventions related to the Millennium Development Goals. The program identifies the best strategies for improving health in low-income countries, using a standard set of methodological assumptions. These studies evaluate interventions in many areas, including child health and HIV/AIDS.For some of these treatments, drug costs are a significant variable: if the drug price doubles, the intervention becomes less cost effective. But if the drug price is reduced by 90%, then more therapies become affordable.Drug prices are uniquely susceptible to radical price reductions through generic competition. Patented pharmaceuticals may be priced at more than 30 times the marginal cost of production; the excess is the patent rent collected by the drug company while the patent and exclusive marketing periods remain. Patent rents are significant. AIDS drugs which sell for US$10,000 per person per year in the US are sold generically for less than US$200. If patented drugs could be sold at the marginal cost of production, cost effective treatments would become even more attractive, and other interventions would become affordable.


2018 ◽  
Author(s):  
John Ojal ◽  
Ulla Griffiths ◽  
Laura L. Hammitt ◽  
Ifedayo Adetifa ◽  
Donald Akech ◽  
...  

AbstractIntroductionMany low income countries soon will need to consider whether to continue pneumococcal conjugate vaccine (PCV) use at full costs as they transition from Gavi support. Using Kenya as a case study we assessed the incremental cost-effectiveness of continuing PCV use.MethodsWe fitted a dynamic compartmental model of pneumococcal carriage to annual carriage prevalence surveys and invasive pneumococcal disease (IPD) incidence in Kilifi, Kenya, and predicted disease incidence and related mortality for either continuing PCV use beyond 2022, the start of Kenya’s transition from Gavi support, or its discontinuation. We calculated the costs per disability-adjusted-life-year (DALY) averted and associated prediction intervals (PI).ResultsWe predicted that overall IPD incidence will increase by 93% (PI: 72% - 114%) from 8.5 in 2022 to 16.2 per 100,000 per year in 2032, if PCV use is discontinued. Continuing vaccination would prevent 15,355 (PI: 10,196–21,125) deaths and 112,050 (PI: 79,620– 130,981) disease cases during that time. Continuing PCV after 2022 will require an estimated additional US$15.6 million annually compared to discontinuing vaccination. The incremental cost per DALY averted of continuing PCV was predicted at $142 (PI: 85 - 252) in 2032.ConclusionContinuing PCV use is essential to sustain its health gains. Based on the Kenyan GDP per capita of $1445, and in comparison to other vaccines, continued PCV use at full costs is cost-effective. These arguments support an expansion of the vaccine budget, however, affordability may be a concern.FundingFunded by the Wellcome Trust.


Author(s):  
Juliana Calabria de Araujo ◽  
Savia Gavazza ◽  
Thiago Lima Leao ◽  
Lourdinha Florencio ◽  
Hernande Pereira da Silva ◽  
...  

Abstract This paper reviews the recent findings in the detection of SARS-CoV-2 in sewage samples. We discuss how wastewater-based surveillance (WBS) can be used as a complementary tool to help the fight against COVID-19 spread, particularly in low-income countries with low sewage coverage and where the testing coverage is deficient, such as Brazil. One of the major challenges on WBS is the use of different protocols to estimate the number of infected people in a community from the quantification of SARS-CoV-2 in wastewater. Therefore, we assembled and reviewed all the relevant data available to date about this topic. Virus concentration and detection methods were reviewed as well, and some of them can be performed in most of the microbiology and environmental engineering laboratories in low-income countries, as discussed. Moreover, the monitoring and sampling plan should represent the local reality. Thus, we suggest unique strategies for sewage sampling and monitoring in different sewerage network points and the slums, despite the possible logistics difficulties involved. Considering the low levels of sanitation in most urban agglomerates in Brazil, WBS can potentially assume a crucial role as a cost-effective strategy to monitor the circulation of the virus and assess the real prevalence of COVID-19.


2001 ◽  
Vol 24 (3) ◽  
pp. 364-364 ◽  
Author(s):  
Duco A. Schreuder

The beneficial effects of road lighting are often seen as very important. They relate to reducing road accidents and some forms of crime but also enhance the social safety of residents and pedestrians and the amenity for residents. Road traffic in developing countries is much more hazardous than in industrialized countries. Accident rates in ‘low’ income countries may be as much as 35 times higher than in ‘high’ income countries. Thus, it might be much more cost-effective to light roads in the developing world than in the industrialized world. Fighting light pollution is more pressing in developing countries as most of the major high-class astronomical observatories are there. Astronomical observations are disturbed by light from outdoor lighting installations, part of which is scattered in the atmosphere to form ‘sky glow’. The International Lighting Commission CIE has published a Technical Report giving general guidance for lighting designers and policy makers on the reduction of the sky glow.


2021 ◽  
Vol 22 ◽  
Author(s):  
E. Bhargav ◽  
Y. Padmanabha Reddy ◽  
K.B. Koteshwara

Abstract : Malaria, a protozoan disease led to numerous deaths and several new million cases raised due to the development of resistance as per the WHO malaria report 2019. This can be overcome by the development of an effective targeted plant-based delivery system through phytosomes that are effective in permeation and bioavailability to treat infected RBCs (parasitic cells). This review article explained the development of targeted Nanophytosomes to overcome resistance, to improve efficacy. This review paper also emphasized various quality-driven developmental approaches in developing an antimalarial product at a reasonable cost. By implementing molecular modeling techniques in development, a significant phytoconstituent with the capability of acting at the target (receptor or enzymes) of the parasite and the one with the capability to overcome drug resistance against resistant strains of parasites can be identified. Absorption Distribution Metabolism Excretion and Toxicity (ADMET) studies information provide a route to the design and formulation of a potent antimalarial agent. Efficient targeted Nanophytosomal formulations can be formulated by functionalizing or conjugating with suitable targets to direct the phytoconstituent to the infected RBCs thereby achieving complete parasitic eradication. Artificial Neural Network technology (ANN), Quality by Design (QbD), molecular dynamics, and simulation studies implementation improves quality and reduces the cost of the product, as these malarial products are much utilized in low-income countries. Hence it can be concluded that targeted developmental quality-driven approaches implementation is essential for effective malarial treatment.


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