Tag: vaccines

Categories : VaccinesTags :

Zapping Pathogens for Faster, Cheaper Vaccine Production

On By ModernMedia
Photo by Zoltan Tasi on Unsplash

A team of researchers from three Fraunhofer Institutes has developed a method of producing vaccines that is faster, more efficient and more environmentally friendly than the conventional production process.

Vaccines date back to 1796, and the first vaccines were simply pus samples freshly taken from people with cowpox. Gruesomely, the Spanish shipped orphaned children to South America to act as cowpox carriers — the world’s first vaccine shipment. As medicine advanced, scientists were able to isolate viruses and inactivate them. However, this is still a lengthy, expensive process.  

But a new production process for inactivated vaccines is set to make vaccine production faster, more environmentally friendly and more efficient than ever before while also reducing costs. Dr Sebastian Ulbert and Dr Jasmin Fertey from the Fraunhofer Institute for Cell Therapy and Immunology IZI in Leipzig, Frank-Holm Rögner from the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP in Dresden, and Martin Thoma from the Fraunhofer Institute for Manufacturing Engineering and Automation IPA in Stuttgart have been awarded the 2021 Fraunhofer Prize for “Human- and Environment-Centered Technology” on behalf of their teams. 

To date, chemicals have always been used in inactivated vaccine production. The pathogens are stored with toxic chemicals, particularly formaldehyde, until the viral genetic information is completely destroyed and it is incapable of replication. This process is known as inactivation.
However, it has a number of drawbacks. For a start, the chemicals also destroy part of the external structures that the immune system forms antibodies from. Also, industrial-scale vaccine production involves large quantities of toxic chemicals, which are hazardous to humans and the environment. Finally, depending on the virus, it can take weeks to months to actually ‘kill’ it.

Their high-tech approach has none of these disadvantages. “Instead of inactivating the virus with toxic chemicals, we fire electrons at it,” explained Dr Ulbert. “The viral particle [is] almost completely intact. There are no chemicals that we need to dispose of and the entire process takes just a few seconds.” 

But there was a problem. The electrons can only penetrate liquids to less than half a millimetre, losing energy along the way. To reliably kill viruses in the liquid with the electrons, the liquid film has to be no thicker than around 0.1 millimetres—and it must be transported evenly, too. “This required complex equipment technology, which is why we brought Fraunhofer IPA on board,” said Rögner.

At Fraunhofer IPA, Martin Thoma developed two ways to overcome the problem. “The pouch module is suitable for conducting preliminary tests that provide useful information, while the tumbler module is beneficial for larger quantities,” said the physics graduate. On the basis of this setup, Dr Fertey investigated viruses such as influenza, Zika and herpes as well as numerous bacteria and parasites, which were treated with electrons subject to targeted acceleration via the pouch and tumbler module. “We were able to successfully and reliably inactivate all classes of pathogens,” said the delighted biologist.

In about five to seven years, the production modules—which are the size of a refrigerator—could be integrated into pharmaceutical production in order to produce vaccines in a quick, efficient and environmentally friendly process.

Source: Phys.Org

Categories : COVID VaccinesTags :

New High-yield Vaccine Technology Recycles Cell Junk

On By ModernMedia

As the world struggles with COVID vaccine production bottlenecks and scaling issues, a team from Northwestern University synthetic biologists have developed a high-yield vaccine technology, increasing production of protein-based vaccines by a factor of five.

Scaling up COVID vaccine production has proved extremely challenging. Adenovirus vaccines such as AstraZeneca’s need to be cultured in 2000 litre tanks containing human cells and then extracted, while mRNA vaccines like that produced by Pfizer requires very careful mixing, as well as components and only a few companies have the skills to produce them. The promising protein subunit vaccines such as Novavax’s offering may be easier to scale up, but also require specific adjuvant, which uses saponin from the bark of a Chilean tree, Quillaja saponaria, which is also used in other vaccines.

Earlier this year, the researchers introduced a new biomanufacturing platform that can quickly make shelf-stable vaccines at the point of care, ensuring they will not go to waste due to transportation or storage problems. In this new study, the team found that enriching cell-free extracts with cellular membranes—the components needed to made conjugate vaccines—massively boosted yields of its freeze-dried platform.

The new technology can produce 40 000 doses per litre per day of antibiotics or vaccines, costing about $1 per dose. At that rate, the team could use a 1000 litre reactor to generate 40 million doses per day, reaching 1 billion doses in less than a month.

“Certainly, in the time of COVID-19, we have all realized how important it is to be able to make medicines when and where we need them,” said study leader Michael Jewett, a professor of chemical and biological engineering at Northwestern. “This work will transform how vaccines are made, including for bio-readiness and pandemic response.”

The new manufacturing platform—called in vitro conjugate vaccine expression (iVAX)—is made possible by cell-free synthetic biology, a process where a cell’s outer wall (or membrane) is removed, and its internal machinery repurposed. This repurposed machinery is then placed in a test tube and freeze-dry it. The cell-free system is activated by the addition of water, turning it into a catalyst for making usable medicine when and where it’s needed. With a shelf-life of over six months, the platform eliminates the need for complicated supply chains and extreme refrigeration, making it extremely valuable for remote or low-resource settings.

In a prior study, Jewett’s team used the iVAX platform to produce conjugate vaccines to protect against bacterial infections, repurposing molecular machinery from Escherichia coli to make a single dose of vaccine in an hour, at $5 per dose.

“It was still too expensive, and the yields were not high enough,” Prof Jewett said. “We set a goal to reach $1 per dose and reached that goal here. By increasing yields and lowering costs, we thought we might be able to facilitate greater access to lifesaving medicines.”

Prof Jewett and his team found that the cell’s membrane, which is typically discarded in cell-free synthetic biology, was key to solving this. When broken apart, membranes naturally reassemble into vesicles, spherical structures that still carry important molecular information. Studying these vesicles, the researchers discovered that increasing vesicle concentration could be useful in making components for protein therapeutics such as conjugate vaccines, which work by attaching a sugar unit—that is unique to a pathogen—to a carrier protein. 

Normally attaching the sugar unit to the protein is very complex, but the researchers found that the cell’s membrane contained machinery that enabled the sugar to more easily attach to the proteins. When they enriched vaccine extracts with this membrane-bound machinery, the researchers significantly boosted usable vaccine yields.

“For a variety of organisms, close to 30% of the genome is used to encode membrane proteins,” said study co-author Neha Kamat, who is an assistant professor of biomedical engineering at McCormick and an expert on cell membranes. “Membrane proteins are a really important part of life. By learning how to use membrane proteins effectively, we can really advance cell-free systems.”

Source: Phys.Org

Journal information: Improving cell-free glycoprotein synthesis by characterizing and enriching native membrane vesicles, Nature Communications (2021). DOI: 10.1038/s41467-021-22329-3

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Diphtheria Resurfacing as a Threat As it Evolves Antibiotic Resistance

On By ModernMedia

Diphtheria is resurfacing as a threat worldwide as it evolves antibiotic resistance and could escape vaccine containment, scientists warn.

Diphtheria cases in recent years have doubled what they were in previous decades, to 16 651 cases in 2018. Although babies are vaccinated against it in high-income countries, there is less coverage in middle- and low-income countries.

Diphtheria is mainly caused by Corynebacterium diphtheriae, spread by coughs and sneezes or close contact with the infected. Usually, the bacteria cause acute infections, driven by the diphtheria toxin—the main target of the vaccine. However, non-toxigenic C. diphtheria can also cause disease.

A team of researchers from the UK and India used genomics to map infections, including a subset from India, where more than half of the globally reported cases occurred in 2018.

Analysing the genomes of 61 bacteria isolated from patients and combining these with 441 publicly available genomes, the researchers were then able to understand how they spread. They also used this information to assess the presence of antimicrobial resistance (AMR) genes and assess toxin variation.

The researchers found clusters to genetically-similar bacteria isolated from different continents, most commonly Asia and Europe. This indicates that C. diphtheriae has been travelling with humans as they spread across the planet.

The diphtheria toxin ch is encoded by the tox gene, for which the researchers found 18 different variations, of which several had the potential to change the structure of the toxin.

Professor Gordon Dougan from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) said: “The diphtheria vaccine is designed to neutralise the toxin, so any genetic variants that change the toxin’s structure could have an impact on how effective the vaccine is. While our data doesn’t suggest the currently used vaccine will be ineffective, the fact that we are seeing an ever-increasing diversity of tox variants suggests that the vaccine, and treatments that target the toxin, need to be appraised on a regular basis.”

First author Robert Will, a PhD student at CITIID, said: “The C. diphtheriae genome is complex and incredibly diverse. It’s acquiring resistance to antibiotics that are not even clinically used in the treatment of diphtheria. There must be other factors at play, such as asymptomatic infection and exposure to a plethora of antibiotics meant for treating other diseases.”

Erythromycin and penicillin are commonly recommended to treat early-stage diphtheria, although there are other classes capable of it. Variants resistant to six of these classes in isolates from the 2010s were identified by the team.

Study leader Dr Ankur Mutreja from CITIID, said: “It’s more important than ever that we understand how diphtheria is evolving and spreading. Genome sequencing gives us a powerful tool for observing this in real time, allowing public health agencies to take action before it’s too late.
“We mustn’t take our eye off the ball with diphtheria, otherwise we risk it becoming a major global threat again, potentially in a modified, better adapted, form.”

Source: Medical Xpress

Journal information: Will, RC et al. Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheria. Nat Comms; 8 Mar 2021; DOI: 10.1038/s41467-021-21870-5

Categories : Urogenital VaccinesTags :

New Vaccine for UTIs Developed With a Localised Approach

On By ModernMedia

Urinary tract infections (UTIs) are a common complaint, affecting women more than men, with a lifetime prevalence of 50% in women, but so far an effective vaccine has proved elusive. Now, researchers from Duke University have come up with an approach that could result in an workable vaccine.

UTIs are caused by a wide range of Gram-negative and positive bacteria, such as Escherichia coli, and antibiotic resistance coupled with common recurrence makes it a growing health burden. It is thought that the immune response to bladder infections sends more repair cells to deal with the bacterial infection than cells to kill the invading bacteria. Because of this, there are often surviving bacteria that reproduce to cause a subsequent infection.

“Although several vaccines against UTIs have been investigated in clinical trials, they have so far had limited success,” said senior author Professor Soman Abraham at Duke University.

“There are currently no effective UTI vaccines available for use in the U.S. in spite of the high prevalence of bladder infections,” Prof Abraham said. “Our study describes the potential for a highly effective bladder vaccine that can not only eradicate residual bladder bacteria, but also prevent future infections.”

According to lead author Jianxuan Wu, PhD, “the new vaccine strategy attempts to ‘teach’ the bladder to more effectively fight off the attacking bacteria. By administering the vaccine directly into the bladder where the residual bacteria harbour, the highly effective vaccine antigen, in combination with an adjuvant known to boost the recruitment of bacterial clearing cells, performed better than traditional intramuscular vaccination.”

The study found that mice immunised in this way effectively fought off infecting E. coli, eliminating all residual bladder bacteria. This suggests that the site of administration could be important for determining vaccine effectiveness.

“We are encouraged by these findings, and since the individual components of the vaccine have previously been shown to be safe for human use, undertaking clinical studies to validate these findings could be done relatively quickly,” Prof Abraham said.

Source: Medical Xpress

Journal information: Jianxuan Wu el al., “Local induction of bladder Th1 responses to combat urinary tract infections,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2026461118

Categories : Immune System VaccinesTags :

Discovering Antibodies That Are Safe And Effective Against Zika

On By ModernMedia

The Zika outbreak of 2015 and 2016 left lasting consequences for children who were in the womb when their mothers were infected with the virus, and now researchers are investigating a safe vaccine that will not negatively interact with certain other viruses.

Zika is a flavivirus, a family which includes dengue, West Nile, and yellow fever virus. In order to protect against these and other pathogens, “we have the ability to make a huge diversity of antibodies, and if we get infected or vaccinated, those antibodies recognise the pathogen,” explained first author Shannon Esswein, a graduate student at the California Institute of Technology.

However, when getting sick with a virus a second time, the body’s own immune response can worsen the situation. Known as antibody-dependent enhancement (ADE), this is when the antibodies stick to the outside of the virus but not neutralising its ability to lock onto cells. This can inadvertently help the virus to infect more cells by letting it enter cells the antibodies are sticking to. A recent study sought to investigate whether this could happen with monoclonal antibody treatments for COVID.

In order to prevent ADE when creating a vaccine, knowing how antibodies adhere to a specific virus is crucial for scientists. In the case flaviviruses, this is especially important as antibodies that protect against one flavivirus may also stick to, but not protect against other flaviviruses, raising the risk of ADE. Antibodies generated in response to a Zika virus vaccine could trigger ADE, if that person is exposed to other flaviviruses such as dengue.

To understand this, the researchers looked at a portion of the flavivirus called the envelope domain III protein, which has been shown to be an important target for protective antibodies fighting flavivirus infections. They studied how those antibodies changed over time as they matured and became better able to adhere to the Zika virus. They also looked at how the antibodies cross-reacted with other flaviviruses, including the four dengue virus types. Their results showed that the Zika antibodies also tightly stick to and defend against dengue type 1, but only weakly stick to West Nile and dengue types 2 and 4. “The weak cross-reactivity of these antibodies doesn’t seem to defend against those flaviviruses, but also doesn’t induce ADE,” Esswein said. These results suggest that the envelope domain III could be a useful basis for a safe vaccine. They also described structures demonstrating how two antibodies recognise Zika and West Nile envelope domain III.

The study results demonstrate how the body mounts “a potent immune response to Zika virus,” said Esswein. Insights gained on the antibodies involved in this immune response will aid the development of new vaccines.

Source: Medical Xpress

Journal information: Shannon R. Esswein et al. Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.1919269117

Categories : COVID VaccinesTags :

Why It’s So Hard to Compare Vaccines

On By ModernMedia

While the world is looking to vaccinations to end the COVID pandemic, a MedPage Today article explains that even with vaccines that have high efficacy, ending transmission is not guaranteed, and there are a lot of differences between simple figures like 94% for Pfizer and 95% for Moderna vaccines.

Firstly, asymptomatic cases are not tracked, simply because assembling tens of thousands of people for a clinical trial is a monumental logistic task, and in the current pandemic, a race against time.

Internist Jeffrey Carson, MD, who managed the Johnson & Johnson COVID vaccine trial’s site at Rutgers University in New Jersey, explained to MedPage Today that it would be difficult but not impossible to create a vaccine trial that provided rapid data about asymptomatic cases.

“You might have people swab themselves every couple days, or every week. You’ll be picking up a lot of disease that way, and you’ll be able to see if the vaccine prevents asymptomatic disease,” Dr Carson said. The current Novavax trial, for example, only asks participants to test themselves for COVID with provided swabs if they believe they are developing symptoms. The Novavax vaccine had also prompted alarm as it was only 49.4% effective against the B501Y.V2 variant, its efficacy reduced by the low rate of protection for HIV positive participants.

The New York Times explained that efficacy is merely how well a vaccine did in a clinical trial, effectiveness is how well it performs in the real world.
Vaccine statistics are difficult even for medical experts to grasp. An infectious diseases expert wrote in a letter to the Lancet explaining that they had misunderstood what 94% to 95% efficacy means for Moderna and Pfizer vaccines and asymptomatic spread.

“It does not mean that 95% of people are protected from disease with the vaccine — a general misconception of vaccine protection.” Instead, it “means that in a population such as the one enrolled in the trials, with a cumulated COVID-19 attack rate over a period of 3 months of about 1% without a vaccine, we would expect roughly 0.05% of vaccinated people would get diseased [with symptomatic infections]. … Accurate description of effects is not hair-splitting; it is much-needed exactness to avoid adding confusion to an extraordinarily complicated and tense scientific and societal debate around COVID-19 vaccines.”

A further problem for scientists is that viral diseases can spread to people unaware that they are infected, something they are still working on understanding. “It makes a lot of sense for survival of the invaders, if you think about it. Humans who feel unwell are not going out to meet up with others, but ones who feel fine will continue along with their daily schedules, allowing the infection to spread,” Bryn Boslett, MD, an infectious disease physician at the University of California San Francisco, told MedPage Today.

Regardless of how well vaccines interrupt the transmission of COVID, it’s important that mask-wearing, social distancing and disinfecting habits are maintained.

“One major worry going forward is that vaccinated people will change their behaviour and stop taking COVID-19 precautions,” Dr Boslett said. “It’s very tempting to do so, very understandable. However, the stars are not yet aligned for us to go back to ‘normal.’ There is still a lot of COVID-19, and most of us are still vulnerable. We need to continue to focus on behavior to reduce new cases of COVID-19.”

Source: MedPage Today

Categories : Diseases, Syndromes and Conditions Paediatrics VaccinesTags :

Researchers Say New Vaccines Needed for Childhood Pneumonia

On By ModernMedia


Research in Australia on new pneumonia vaccines show that while pneumonia in children is being suppressed,  empyaema is increased.

The research, which was led by the University of New South Wales (UNSW), examined the impact of the new 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyaema.
Empyaema, which is the collection of pus in the lungs, occurs in about 1% of children with pneumonia. In children, empyaema is far less fatal than it is in adults, but it does extend hospitalisation, requiring antibiotics and surgery or installation of a drain.
The findings of the study showed that while 13vPCV resulted in a 21% drop in childhood pneumonia hospitalisations, there was a contemporaneous 25% rise in empyaema hospitalisations.

According to senior author Professor Adam Jaffe, Head of the School of Women’s and Children’s Health at UNSW Medicine & Health, said the findings suggested an emergence of non-vaccine serotypes—those which 13vPCV does not cover.

13vPCV was introduced to cover the 13 most common serotypes that cause invasive pneumococcal infection, adding six more serotypes over the seven serotypes covered by its predecessor, 7cPCV.

Prof Jaffe said: “Although we found a substantial reduction in serotype 1, serotype 3 is now the predominant organism which causes childhood empyema—in 76% of cases—so, efforts must be made to create a vaccine which is more effective against serotype 3.

“In fact, Australia recently changed the vaccination dosage schedule to try and improve the effectiveness of 13vPCV against serotype 3, but we need to continue monitoring patients using molecular techniques to see if this change has had an impact.

“Childhood bacterial pneumonia and empyema are potentially preventable diseases through vaccination. So, if Australia can develop an effective vaccine, we could prevent children from being hospitalized with pneumonia and empyema.”

The researchers conducted a similar study over four years during the 7vPCV era.   

“Our new study had two parts,” Prof Jaffe said. “We analysed national hospitalisations for childhood empyaema and childhood pneumonia, then we conducted an enhanced surveillance study on children with empyaema.”

The first part of the research used publicly available hospitalisations data to find out if the introduction of 13vPCV changed how many children were admitted to hospital with pneumonia and empyaema.

The enhanced surveillance study involved the collection of blood and lung fluid samples from 401 children  with empyaema, followed by molecular testing on these samples and comparing the results to their previous study undertaken during the period of 7vPCV.

Prof Jaffe said research with a larger sample was ongoing, and 13vPCV monitoring was needed.

Source: Medical Xpress

Journal information: Roxanne Strachan et al. Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in Australia, Thorax (2021). DOI: 10.1136/thoraxjnl-2020-216032

Categories : Medical Research & TechnologyTags :

New Biomaterials Could Boost Vaccines or Self-sterilise PPE

On By ModernMedia

Researchers from the Indian Institute of Science describe two technologies currently being researched that could be of great benefit in fighting viruses.

These technologies could enhance the effectiveness of vaccines, and also make surfaces destructive to viruses.

“It is important not just in terms of COVID,” explained author Kaushik Chatterjee. “We’ve seen SARS, and MERS, and Ebola, and a lot of other viral infections that have come and gone. COVID has, of course, taken a different turn altogether. Here, we wanted to see how biomaterials could be useful.”

The technologies combine the field of biomaterials, which are designed to interact with biological systems, along with nanotechnology, where structures are engineered on a tiny scale. Biomaterials have been used for dental implants and joint replacements, while nanotechnology has been harnessed for drug delivery systems.

One application the authors describe is the combination of nanotechnology and biomaterial could be used to prepare the immune system to recognise vaccine antigens.

“It is a means of stimulating the immune cells which produce antibodies during the vaccination,” explained author Sushma Kumari. “It is like a helper, like priming the cells. Now, the moment they see the protein, the cells are more responsive to it and would be secreting more antibodies.”

Another technology application is surfaces that disinfect themselves. By putting an electrical charge onto the surfaces, they could be made into a hostile coating that damages or destroys virus particles when they fall onto them. These surfaces could be used for PPEs and high-touch items such as doorknobs. This would save considerable time, effort and expense in regularly disinfecting surfaces with chemicals or UV irradiation. A similar existing technology is the use of silver nanoparticles as antibacterial medical device coatings.

This technology is very much in its early stages, the researchers stressed. Research needs to be done on which biomaterials are suitable for fighting viruses, and the solution for one disease may not be applicable to another.

Source: Medical Xpress

Journal information: “Biomaterials-based formulations and surfaces to combat viral infectious diseases” APL Bioengineering, DOI: 10.1063/5.0029486