Indian-made 'freeze-free' vaccine carrier to undergo field trials

Agencies
February 9, 2018

New Delhi, Feb 9: This week, the first commercially available freeze-free vaccine carrier will begin introductory field trials in Nepal. This follows the World Health Organisation (WHO) announcement that the Indian-made carrier using PATH's "Freeze-Safe" reference design passed WHO Performance, Quality, and Safety (PQS) laboratory tests for User Independent Freeze Prevention, which prequalifies it for use in global immunisation programs.

This is the first low-cost carrier innovation available to address the widespread and long-standing problem of vaccines freezing in the cold chain during the "last mile" of outreach to infants and children.

Currently in low - and middle - income countries, health workers carry millions of temperature-sensitive vaccines next to ice packs inside vaccine carriers to reduce heat exposure, but this risks freezing the vaccines if ice packs are not conditioned (carefully warmed to around 0°C).

Freezing can irreversibly compromise vaccine potency, resulting in inadequate protection from disease for people receiving vaccines. When health workers suspect temperature damage, the vaccine or medication is often discarded - at great cost to health care programs.

PATH's breakthrough solution mitigates the risk of vaccines being damaged by freezing or heat in carriers and eliminates the step of conditioning ice packs, reducing health worker burden. Frozen ice packs can be inserted immediately into the carrier thanks to a built-in barrier that shields the vaccines from reaching negative temperatures and excessive heat.

Many of the newer vaccines that protect children and infants from life-threatening diseases and infections, such as for human papillomavirus, pneumonia, and rotavirus, are freeze sensitive and cost far more than other vaccines. In 2015, the United Nations Children's Fund (UNICEF) procured approximately USD 1.7 billion worth of vaccines for immunization programs, of which more than USD 1.2 billion were freeze sensitive.

"Our priority is maintaining vaccine potency for the millions of people living in remote communities. In the future, vaccine carriers that prevent freezing will become the new standard for immunization programs," said Pat Lennon, who leads the cold chain team at PATH.

In order to rapidly accelerate introduction of this innovation, PATH put the Freeze-Safe reference design into the public domain for any manufacturer to use in their vaccine carrier products.

PATH staff in Seattle and New Delhi, India, has provided technical advice to three product manufacturers who have adopted the technology. India-based AOV International's product AFVC46 is the first carrier to receive WHO-PQS approval and will be available for purchase through the UNICEF Supply Division catalog.

"The Freeze-Safe vaccine carrier is a great example of Indian industry helping solve a global public health challenge. This 'Made in India' freeze-preventive vaccine carrier can help health workers in India and globally to administer lifesaving vaccines that do not freeze and could help save millions of lives," said Neeraj Jain, Country Director of PATH's India country program.

PATH estimates that more than 2 million new and replacement carriers will be needed by 2020 for the 73 Gavi-member countries. To accelerate scale-up of the Freeze-Safe innovation, PATH is conducting field trials, supporting efforts to integrate the carriers into existing health systems, and working with manufacturers as well as adapting the innovation for use in other cold chain equipment.

"Vaccine carriers that prevent vaccines from freezing while in transit and yet are low cost and easy to use can save millions of children's lives. These are exactly the type of cutting-edge solutions we need to immunize every child," said Dr. Benjamin Schreiber, Deputy Immunization at UNICEF.

PATH has worked to advance technologies, policies, and programs to address vaccine freezing issues across the supply chain from formulation to the last mile since 1996, and on the Freeze-Safe innovation since 2012. This work aligns with UNICEF; Gavi, the Vaccine Alliance; and WHO strategies to maintain vaccine potency and improve immunization cost efficiencies and coverage.

This project was made possible with support from the Bill & Melinda Gates Foundation.

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Agencies
June 12,2020

Global poverty could rise to over one billion people due to the COVID-19 pandemic and more than half of the 395 million additional extreme poor would be located in South Asia, which would be the hardest-hit region in the world, according to a new report.

Researchers from King's College London and Australian National University published the new paper with the United Nations University World Institute for Development Economics Research (UNU-WIDER) said that poverty is likely to increase dramatically in middle-income developing countries and there could be a significant change in the distribution of global poverty.

The location of global poverty could shift back towards developing countries in South Asia and East Asia, the report said.

The paper, 'Precarity and the Pandemic: COVID-19 and Poverty Incidence, Intensity and Severity in Developing Countries,' finds that extreme poverty could rise to over one billion people globally as a result of the crisis.

The cost of the crisis in lost income could reach USD 500 million per day for the world's poorest people, and the intensity and severity of poverty are likely to be exacerbated dramatically.

The report said that based on the USD 1.90 a day poverty line and a 20 per cent contraction, more than half of the 395 million additional extreme poor would be located in South Asia, which would become the hardest hit region in the world mainly driven by the weight of populous India followed by sub-Saharan Africa which would comprise 30 per cent, or 119 million, of the additional poor.

The report added that as the value of the poverty line increases, a larger share of the additional poor will be concentrated in regions where the corresponding poverty line is more relevant given the average income level.

For instance, the regional distribution of the world's poor changes drastically when looking at the USD 5.50 a day poverty line the median poverty line among upper-middle-income countries.

At this level, almost 41 per cent of the additional half a billion poor under a 20 per cent contraction scenario would live in East Asia and the Pacific, chiefly China; a fourth would still reside in South Asia; and a combined 18 per cent would live in the Middle East and North Africa (MENA) and in Latin America and the Caribbean (LAC), whose individual shares are close to that recorded for sub-Saharan Africa.

India plays a significant role in driving the potential increases in global extreme poverty documented previously, comprising almost half the estimated additional poor regardless of the contraction scenario, the report said.

Nonetheless, there are other populous, low and lower-middle- income countries in South Asia, sub-Saharan Africa, and East Asia and the Pacific accounting for a sizeable share of the estimates: Nigeria, Ethiopia, Bangladesh, and Indonesia come next, in that order, concentrating a total of 18 19 per cent of the new poor, whereas the Democratic Republic of Congo, Tanzania, Pakistan, Kenya, Uganda, and the Philippines could jointly add 11 12 per cent.

Taken together, these figures imply that three quarters of the additional extreme poor globally could be living in just ten populous countries.

The report added that this high concentration of the additional extreme poor is staggering , although not necessarily unexpected given the size of each country's population.

On one hand, data shows that three of these ten countries (Ethiopia, India, and Nigeria) were among the top ten by number of extreme poor people in 1990 and remained within the ranks of that group until 2018.

Despite this crude fact, two of these countries have managed to achieve a sustained reduction in their incidence of poverty since the early 1990s, namely Ethiopia and India, reaching their lowest poverty headcount ratio ever recorded at about 22 and 13 per cent, respectively. Nonetheless, the potential contraction in per capita income/consumption imposed by the pandemic's economic effects could erase some of this progress.

The researchers are now calling for urgent global leadership from the G7, G20, and the multilateral system, and propose a three-point plan to address the impact of the COVID-19 on global poverty quickly.

Professor of International Development at King's College London and a Senior Non-Resident Research Fellow at UNU-WIDER Andy Sumner said the COVID-19 crisis could take extreme poverty back over one billion people because millions of people live just above poverty.

Millions of people live in a precarious position one shock away from poverty. And the current crisis could be that shock that pushes them into poverty.

Professor Kunal Sen, Director of UNU-WIDER said the new estimates about the level of poverty in the world and the cost of the COVID-19 pandemic to the world's poor are sobering.

We cannot stand by and see the hard work and effort of so many be eradicated. We will know what the real impact is in time, but the necessary action to ensure we achieve the Sustainable Development Goals by 2030 needs to be planned now, Sen said.

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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Agencies
July 3,2020

Apart from the many benefits of doing exercise, new research has now found that exercise can slow down or prevent the development of macular degeneration and may benefit other common causes of vision loss, such as glaucoma and diabetic retinopathy.

The new study from the University of Virginia School of Medicine found that exercise reduced the harmful overgrowth of blood vessels in the eyes of lab mice by up to 45 per cent. This tangle of blood vessels is a key contributor to macular degeneration and several other eye diseases.

The study represents the first experimental evidence showing that exercise can reduce the severity of macular degeneration, a leading cause of vision loss, the scientists report. Ten million Americans are estimated to have the condition.

"There has long been a question about whether maintaining a healthy lifestyle can delay or prevent the development of macular degeneration. The way that question has historically been answered has been by taking surveys of people, asking them what they are eating and how much exercise they are performing," said researcher Bradley Gelfand, PhD, of UVA's Center for Advanced Vision Science.

"That is basically the most sophisticated study that has been done. The problem with that is that people are notoriously bad self-reporters ... and that can lead to conclusions that may or not be true. This [study] offers hard evidence from the lab for the very first time," Gelfand added.

Enticingly, the research found that the bar for receiving the benefits from exercise was relatively low - more exercise didn't mean more benefit.

"Mice are kind of like people in that they will do a spectrum of exercise. As long as they had a wheel and ran on it, there was a benefit. The benefit that they obtained is saturated at low levels of exercise," Gelfand said.

An initial test comparing mice that voluntarily exercised versus those that did not found that exercise reduced the blood vessel overgrowth by 45%. A second test, to confirm the findings, found a reduction of 32 per cent.

The scientists aren't certain exactly how exercise is preventing the blood vessel overgrowth. There could be a variety of factors at play, they say, including increased blood flow to the eyes.

Gelfand, of UVA's Department of Ophthalmology and Department of Biomedical Engineering, noted that the onset of vision loss is often associated with a decrease in exercise.

"It is fairly well known that as people's eyes and vision deteriorate, their tendency to engage in physical activity also goes down. It can be a challenging thing to study with older people. ... How much of that is one causing the other?" he said.
The researchers already have submitted grant proposals in hopes of obtaining funding to pursue their findings further.

"The next step is to look at how and why this happens, and to see if we can develop a pill or method that will give you the benefits of exercise without having to exercise," Gelfand said.

He explained, "We're talking about a fairly elderly population [of people with macular degeneration], many of whom may not be capable of conducting the type of exercise regimen that may be required to see some kind of benefit." (He urged people to consult their doctors before beginning any aggressive exercise program.)
Gelfand, a self-described couch potato, disclosed a secret motivation for the research: "One reason I wanted to do this study was sort of selfish. I was hoping to find some reason not to exercise," he joked. "It turned out exercise really is good for you."

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