Category: Vaccines

Millions of J&J Vaccines for South Africa Unfit for Use

In yet another blow to South Africa’s flagging vaccination programme, millions of the Johnson & Johnson vaccine doses meant to be used have been declared unfit for use. This is due to contamination concerns at one of the group’s facilities in the US.

The US Food and Drug Administration said that the doses were not suitable for use. Upon reviewing this decision, the South African Health Products Regulatory Authority (SAHPRA) said in a statement that it had decided “not to release vaccine produced using the drug substance batches that were not suitable”.

J&J’s Emergent plant was ordered to pause production in April several weeks after it was determined that batches of a substance used to produce the vaccine were cross-contaminated with ingredients from another jab made by Anglo-Swedish pharma giant AstraZeneca. The FDA is yet to allow the factory to reopen.

Acknowledging the setback in South Africa’s vaccination programme, acting Health Minister Mmamoloko Kubayi-Ngubane said Saturday that the batches concerned were stored in a high-security laboratory in Port Elizabeth belonging to drugmaker Aspen. Aspen meanwhile promised that it is ramping up production elsewhere to meet the shortfall, and President Ramaphosa said that he discussed with President Biden the possibility of receiving US vaccine donations.

Along with other countries South Africa, is pushing for a patent waiver on COVID vaccines to allow low cost production of generics.

“If we are to save lives and end the pandemic, we need to expand and diversify manufacturing and get medical products to treat, combat and prevent the pandemic to as many people as quickly as possible,” President Cyril Ramaphosa told the G7 group of wealthy nations meeting in Britain on Sunday. The country needs 31 million doses of the J&J vaccine to help vaccinate its population of 59 million.

South Africa has secured 30 million doses of the highly effective Pfizer-BioNTech vaccine, but is a two-dose vaccine which has significant cold chain requirements.

Emergency shipment

SAHPRA stated that there is a new delivery of approximately 300 000 J&J doses “that have been cleared by the US FDA that meet the requirements and will subsequently be released and shipped to South Africa.” The expiry date of these doses have been extended, and will be ready for administration to South African teachers within days.

Vaccinations were already paused in April after reports of rare cases of blood clots. And in February, South Africa rejected over 1.5 million doses of AstraZeneca’s vaccine as it was deemed ineffective. The J&J vaccines were already facing expiry as they had been removed from long term storage.

South Africa has only vaccinated just over 1% of its population but as far as can be ascertained with limited testing in Africa is the hardest hit by COVID on the continent, with over 1.7 million recorded cases.
Source: Eyewitness News

ImmunityBio Vaccine Trial Expanding in Western Cape

In addition to traditional subcutaneous administration for the vaccine candidate, the trial will measure immune responses generated by sublingual and nasal administration routes. Photo by Gustavo Fring from Pexels

The Phase I clinical trial of ImmunityBio’s experimental COVID vaccine, designed to be effective against COVID variants, is about to be expanded to include different administration routes as well as effectiveness in people who previously had COVID. 

Co-investigator Prof Graeme Meintjes, second chair in the Department of Medicine at UCT, said that the Phase I trial has started and is still ongoing at the Wellcome Centre for Infectious Diseases Research in Africa’s (CIDRI-Africa) Khayelitsha clinical research site.

He said that the first two cohorts of ten participants each both received two subcutaneous injections of the vaccine, three weeks apart, with one cohort receiving a higher dose.

“The purpose of that was to assess safety, so participants were followed up very carefully for side effects and for reactions to the vaccine. And the review of that suggests no major safety concerns,” he explained. He added that the Phase I trial design has since been adapted to include four more cohorts, which is going through the approval process.
These four additional cohorts will include people who have had COVID because the researchers want to look at the effect the vaccine will have on boosting existing immunity against COVID. Each cohort will have ten participants, bringing the expected total number of participants for Phase I to 60 people.

New administration routes

To see whether different administration routes produce a sufficient immune response, each participant in these new cohorts will receive one dose of the vaccine through one of four routes. These would be either a subcutaneous injection, a sublingual route, a combination of subcutaneous injection and sublingual method, or an intranasal route.

“We’ll be measuring the antibody responses as well as the T-cell responses to the vaccine, but we do not have results yet,” said Meintjes. He added that enrolment should be complete in the next two months, pending the outcome of the approval process.

Phase II/III trial plans

Phase II and Phase III trials in South Africa are being planned, which will be headed by the South African Medical Research Council (SAMRC), Mentjes confirmed.

Details will be made available once the trial has been approved by SAHPRA. It is unlikely that placebos will be used, now that vaccines are shown to be effective; rather different vaccines will be compared.

Broader immune response with two-pronged defence

The vaccine has been designed to potentially offer a broader, long-lasting immune response, Mentjes noted. In this way it should also provide improved protection against COVID variants.

Currently, most of the COVID vaccines are designed to produce an immune response against the spike protein of the virus, but it mutates rapidly, allowing certain variants to partially or fully escape vaccines. 

The ImmunityBio vaccine aims to offer a two-pronged or dual defence, Meintjes said, with the vaccine containing two proteins from the SARS-CoV-2 virus: the spike protein along with the more stable nucleocapsid protein. The nucleocapsid is an RNA-binding protein which is critical for viral replication and genome packaging.

He explains that targeting nucleocapsid could potentially provide more durable and long-term protection against different variants of the SARS-CoV-2 virus because the immune system will recognise the nucleocapsid even when the spike protein changes.

“The hope is that by including the nucleocapsid you would generate a vaccine response that covers emerging variants, those that have emerged and those that might emerge in the future,” he says.

Human-adenovirus based vaccine carrier

The ImmunityBio vaccine will use an adenovirus vector to deliver the antigens. Director of the Africa Health Research Institute (AHRI), Professor Willem Hanekom, explained that a vector is needed in order to stimulate the immune system’s response, and a viral vector is effective since it is foreign to the immune system, helping provoke an immune response. The virus is designed to simply carry the antigens into the body.

The AstraZeneca vaccine uses a modified chimpanzee adenovirus while Johnson & Johnson’s uses the human adenovirus Ad26, which has been used before in a number of vaccines including HIV. ImmunityBio’s vaccine uses the human adenovirus hAd5, which was initially used in failed gene therapy trials — but which proved to be an excellent vaccine delivery system. However, its development over the past two decades has been halting.

According to Prof Hanekom, if there is previous immunity against the adenovirus being used in a vaccine, the immune system will destroy it before the antigens inside are released. This has been circumvented with the ImmunityBio vaccine so that the immune system doesn’t immediately recognise the hAd5 vector. There was concern that the Johnson & Johnson vaccine would have limited efficacy in sub-Saharan Africa due to the fact that about half the population have immunity to Ad26.

“They’ve modified the adenovirus so it will still work and still be seen by the immune system even if there is pre-existing immunity because they’ve taken out the parts that the pre-existing immunity sees,” Prof Hanekom said.

Enhanced T-cell response

The vaccine is specifically designed to elicit strong T-cell responses to the nucleocapsid, and this has been seen in animal studies, Mentjes noted.

“Obviously one purpose of these studies is to see whether this design element generates those strong T-cell responses in humans as well,” he says. “All COVID vaccines elicit T and B cell responses, it’s not one or the other. But this (vaccine) is specifically designed to enhance those T-cell responses.”

B-cells and T-cells form part of the body’s adaptive immune response. B-cells form the antibodies to respond to a pathogen, and when the virus is introduced again, memory B-cells provide the antibodies to respond quickly.

Vardas says that with the ImmunityBio vaccine, B-cells and memory B-Cells will be formed that will remember the spike protein and the nucleocapsid and how to attack it. She likens this to a sniper attack. She explains that when a memory B-cell detects the spike or nucleocapsid protein, it signals for the production of B-cell antibodies. These antibodies then coat the outside of the virus, which signals the T-cells to attack and essentially “eat up” the virus-infected cells.

There are two types of T-cells, explains Vardas – CD4 cells which attack the virus, and CD8 cells, which also form a memory cell as the B-cell does. “You’ll have groups of CD4 and CD8 cells that are spike protein-specific and groups that are nucleocapsid specific, so improving that kind of attack to two sides of the war,” said Vardas.

Source: University of Cape Town

Vaccine Flops and Shortages Leave SA with no Covax Shots

Image by Quicknews

Nearly six months after South Africa’s first procurement deal was made with the Covid-19 Vaccines Global Access (Covax) programme, but vaccine flops and shortages in supply have left South Africa empty-handed, while Covax struggles to even meet its June delivery goal.

South Africa’s vaccine rollout has been anything but smooth. The first batch of vaccines, produced by the Serum Institute of India (SII), arrived in the country on 1 February but were abandoned a week later after a study found it was ineffective against the 501Y.V2 variant. That first batch of one million doses were sold onto the African Union (AU) and the remainder of the order refunded.

The health department switched to the Johnson & Johnson (J&J) single-dose shot and vaccinated nearly half a million healthcare workers until its use was also halted over blood clot concerns. Phase 2 of the rollout is using the Pfizer vaccine. Fortunately, it has been found that it can be stored at much higher temperatures than its previous ultracold requirements, making it easier to distribute.

However, the failure to join Covax by December 2020 was an early warning sign over the government’s handling of vaccine acquisition. The Covax iniative, led by the Vaccine Alliance (Gavi) and World Health Organization (WHO) to supply vaccines to poorer nations, were expected to kickstart South Africa’s rollout.

Missing that first deadline, the health department and Solidarity Fund confirmed, on 22 December 2020, that a down payment of R283 million had been made to secure doses through Covax.

Vaccine flip-flopping
At first, South Africa was to receive almost 2.5 million doses of AstraZeneca vaccine, but the country’s decision to abandon the use of AstraZeneca caused severe delays. The country’s allocated AstraZeneca doses were taken back into the Covax programme.

“South Africa was allocated 2 426 400 doses of the AstraZeneca vaccine… it has requested to be allocated another vaccine in place of AZ, and will receive allocations of alternative vaccines instead,” Gavi spokesperson Evan O’Connell told Business Insider South Africa.

“It has already been allocated, at this stage, 1,392,300 doses of the Pfizer vaccine, allocated for Q2 2021.”

According to Covax’s first-round schedule,  South Africa was due to receive 117 000 Pfizer doses before April. But Covax’s deliveries are falling behind, putting initiative’s ability to meet its second quarter target.

On 17 May UNICEF Executive Director, Henrietta Fore announced that the Covax facility would shortly have delivered 65 million doses, which should have been 170 million doses by that time.

“By the time G7 leaders gather in the UK next month, and as a deadly second wave of COVID will likely continue to sweep across India and many of its South Asian neighbours, the shortfall will near 190 million doses.”

Covax hamstrung by Indian COVID crisis

India’s COVID crisis has hamstrung Covax’s aim of delivering 237 million doses of AstraZeneca vaccine in the first half of 2021. With India having the world’s highest infection numbers and deaths since April, the SII, which produces AstraZeneca doses for Covax, announced that it would halt foreign supply until December at the earliest.

“We continue to scale up manufacturing and prioritise India,” said SII CEO Adar Poonawalla on 18 May. “We also hope to start delivering to Covax and other countries by the end of the year.”

At only 35% of its targeted vaccine deliveries, Covax is calling for renewed funding and donations from developed nations — who are also accused of hoarding vaccines. WHO director-general Tedros Adhanom Ghebreyesus, criticised wealthy nations for continuing a “scandalous inequity” on Monday.

“We need countries to donate tens of millions of doses of vaccines immediately through Covax, which is the agreed global mechanism for distributing vaccines,” stated Ghebreyesus.

“We need companies to help make donations happen fast, and to give Covax the first right of refusal on all uncommitted doses now, in 2021.”

It’s unclear whether the SII’s decision to halt its supply will result in reallocations of the Pfizer doses, on which SA is depending, and which therefore could result in further delays for its Covax-allocated doses.

Source: Business Insider

Low Leptin Levels Can Stifle Response to Vaccines

Image source: NCI on Unsplash

Reduced levels of leptin, a metabolic hormone, is linked to poor vaccine antibody responses in the general population, according to research by the University of Queensland.

The researchers made the discovery while investigating the response of several cohorts to the influenza vaccine or hepatitis B vaccine prior to COVID.

Professor Di Yu at the University of Queensland identified a link between the metabolic and immune systems that could be exploited to develop new strategies for improving vaccine protection in vulnerable populations.

“Using multiple advanced techniques in immunology, genetics and biochemistry, our study found leptin directly promoted the development and function of cells which are vital in triggering an antibody response,” Professor Yu said.

“In collaboration with global teams, we identified the reduction of an essential metabolic hormone called leptin was associated with compromised vaccine responses in both young and older individuals.

“As a result, we can now identify those who are at risk of not generating an antibody response after vaccination.”

Leptin is a metabolic hormone mostly produced by fat tissue.

“Vaccines have been known for a very long time to have a different efficacy for individuals,” he said.

“Although our genetics partially contribute to the difference, other factors are also essential. When we are fit and healthy, we have a much better vaccine efficacy.

“If we are healthy, we have a good metabolism and a normal level of leptin, but if we have malnutrition or some disease conditions, we may have a low level of leptin, which may limit our vaccine response and immune protection.”

Professor Yu said that one subject was future research was that many people with obesity and high levels of leptin conversely often had leptin resistance, which could also potentially lead to a poorer vaccine response.

The researchers are hoping to test responses to the COVID vaccines to find biomarkers that could identify people who may not mount a strong vaccine response.

“During the era of the COVID pandemic, the successful vaccination for SARS-CoV-2 is the major hope to bring society back to normalcy. Differing vaccine responses cause a major bottleneck in large-scale vaccination programs,” said Professor Yu.

Source: News-Medical.Net

.Journal information: Deng. J., et al. (2021) The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses. Nature Communications. doi.org/10.1038/s41467-021-23220-x.

South Africa to Sign On to Digital ‘Vaccine Passport’

Photo by Blake Guidry on Unsplash

Transport minister Fikile Mbalula said that South Africa will seek to join a digital ‘vaccine passport’ scheme being tested by a number of airlines.

Presenting his departmental budget speech on Friday, Mbalula said that South Africa must ensure that it joins the growing number of countries that accepts the International Air Transport Association’s (IATA) mobile travel pass for COVID vaccination.

This particular initiative was tested successfully by Singapore Airlines, and more than 20 carriers, the minister said.

“In recent months, Singapore has announced that it will accept visitors who use a mobile travel passes containing digital certificates for Covid-19 tests and vaccines,” Mbalula said.

“This makes Singapore one of the first countries to adopt this initiative. Singapore will accept the IATA mobile travel pass for pre-departure checks, where travellers can get clearance to fly to and enter Singapore by showing a smartphone application containing their data from accredited laboratories.”

The IATA’s app allows travellers to store digital information from certified labs. It will be available for download later this month. IATA aims to bring in additional changes such as QR code scanning by immigration officers.

Vaccine passports have been the subjects of debates over equitability, access and potential for abuse. However, vaccine passports are not only permissible under international health regulations, they already exist. The World Health Organization endorses certificates confirming vaccination against yellow fever for entry into certain countries. They also incentivise vaccination, a public good.

Currently, South Africa has 62 ‘major restrictions’ from other countries in place, with suspended travel, stringent requirements for entry or outright bans. Meanwhile there are 92 moderate restrictions in place on South Africa, where travel is possible subject to measures such as COVID tests on arrival.

Source: BusinessTech

Second Gen COVID Vaccine Considered for Booster Shot in SA

Image source: Pexels/CC0

A second generation viral vector COVID vaccine candidate from ImmunityBio Inc is being considered as a booster shot in a study involving nearly 500 000 South African health workers already innoculated with the Johnson & Johnson vaccine.

The health workers, who are the first outside of much smaller studies to receive vaccinations in South Africa, will need a booster, Glenda Gray, the co-lead of the South African studies, said in an interview Wednesday.

“It could be the universal boost that we are looking for,” she said. “Hopefully we will start in a couple of weeks.”

ImmunityBio’s second generation COVID vaccine candidate uses an hAd5 virus as vector. It induces both short term and long term immunity, and besides targeting the coronavirus’ spike proteins like first generation vaccines, it also targets the nucleocapsid protein, which has a lower rate of mutations. Additionally, this hAd5 vector virus provokes an anti-SARS-CoV-2 response, even in individuals with adenovirus immunity.

The magnitude of this T cell response was equivalent to those seen for spike and nucleocapsid T cell responses from previously infected convalescent SARS-CoV-2 patients.

The robust T cell response to both proteins could make it more effective against strains such as the B.1.351 ‘South African’ variant , ImmunityBio said in a statement earlier this year.

The vaccine is also being assessed to determine the safety and effectiveness of oral, sublingual and subcutaneous administration routes.

ImmunityBio’s vaccine is currently in phase I trials in Cape Town, and the company has signed an agreement with South Africa’s BioVac Institute to produce the inoculation in the country should it win approval.

Source: BusinessTech

Zapping Pathogens for Faster, Cheaper Vaccine Production

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

New High-yield Vaccine Technology Recycles Cell Junk

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

After Receiving Vaccine, Queen Elizabeth Encourages Others

After receiving her COVID vaccine, Queen Elizabeth encouraged those who were wary to think of others and do the same.

She and Prince Philip received their vaccine in the initial wave of vaccinations for the elderly in the UK. Prince Philip, 99,  is currently in hospital for a non-COVID related illness. There are concerns about the health of her husband Prince Philip, but the palace says that he is responding to treatment, but likely to remain in hospital for a few more days.

“Once you’ve had a vaccine you have a feeling of you know, you’re protected which I think is very important and as far as I could make out it was quite harmless,” the 94-year old monarch queen said in a video call with health officials supervising inoculations across the UK.

“It was very quick, and I’ve had lots of letters from people who have been very surprised by how easy it was to get the vaccine. And the jab – it didn’t hurt at all,” she added, likening the virus to a plague.

Earlier this week, the UK’s vaccine minister said that 11% to 15% of people were hesitant about receiving a vaccine, especially among minority groups.

“It is obviously difficult for people if they’ve never had a vaccine because they ought to think about other people other than themselves,” said the queen.

She praised the “remarkable” Britain’s rollout of the vaccination, one of the world’s fastest. Other members of the royal family including Prince Charles and his son Prince William, have been visiting vaccination centres over the last two weeks to convey their thanks to staff and volunteers for their work.

Data from Public Health England suggest that the vaccines are 80% effective in preventing serious COVID in the elderly.

Source: Reuters

New Vaccine for UTIs Developed With a Localised Approach

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