Category: Vaccine

Hospitalization is supposed to make people well. But on a given day, an estimated 1 in 31 hospitalized patients contracts an infection from the hospital itself, and tens of thousands die annually. Many of these infections are antibiotic-resistant, and treating them contributes to the evolution of new "superbugs."

But now, researchers have a new idea for preventing hospital-acquired infections: a vaccine that puts the immune system on short-term high alert for a broad array of pathogens.

The vaccine, so far tested only in mice, activates the innate immune system, the body's first line of defense, according to a study published Oct. 4 in the journal Science Translational Medicine. The innate immune system is not specific to any particular pathogen, and its protection tends to fade faster than that of the adaptive immune system, which "remembers" viruses and bacteria it has encountered in the past. (Most vaccines train the adaptive immune system to fight off specific diseases, such as the seasonal flu or COVID-19.)

But for hospitalized patients, broad and short-term protection is needed most, said Brad Spellberg, the senior study author and chief medical officer at the Los Angeles General Medical Center.

"It solves a problem that traditional vaccines have not been able to solve," Spellberg told Live Science.

Related: Dangerous 'superbugs' are a growing threat, and antibiotics can't stop their rise. What can?

There are too many potential hospital-acquired pathogens to reasonably vaccinate incoming patients for each individual bacterium or fungus, Spellberg said. And in any case, traditional vaccines require time to activate adaptive immunity, and hospitalized patients need immediate protection.

The researchers stumbled across the idea for the new vaccine more than 15 years ago while looking to develop a traditional vaccine for Staphylococcus aureus, a common source of hospital infections. Certain strains of the bacterium, known as methicillin-resistant S. aureus (MRSA), are resistant to common antibiotic treatments.

The researchers were struggling to find a combination of bacterial proteins that would protect against staph infections in the blood, so they began adding a series of compounds called adjuvants to their formulation. Adjuvants are ingredients that broadly boost the immune response to a desired target.

Eventually, the researchers found a combination of three bacterial proteins and three adjuvants that worked in animal studies. But during testing, they found that giving mice a vaccine with only the three adjuvants was just as protective as giving them the vaccine with proteins and adjuvants combined.

"We were like, 'Whoa, whoa, whoa, what is going on here?'" Spellberg said.

What was going on, another decade of testing revealed, was that the vaccine was not specifically targeting the staph proteins. Rather, it was boosting the activity of the innate immune system more broadly and that was enough to protect the mice from staph infection.

"It's an important and exciting concept for a vaccine," said Marcela Henao Tamayo, an immunologist at Colorado State University who was not involved in the new study.

The three adjuvants aluminum hydroxide, monophosphoryl lipid A, and fungal mannan protected mice against not only S. aureus but also strains of other common hospital-acquired pathogens with various degrees of antibiotic resistance, such as Enterococcus faecalis, Escherichia coli, Acinetobacter baumannii and Klebsiella pneumoniae. The vaccine also protected against the fungi Rhizopus delemar and Candida albicans, which also frequently affect hospitalized people.

Related: Cleaning product residues may be driving a deadly superbug's antibiotic resistance

Aluminum hydroxide and monophosphoryl lipid A are already used in vaccines and approved by regulatory agencies in both the U.S. and Europe, Spellberg said. Mannan, a component of fungal cell walls, is not yet an approved vaccine adjuvant, but it has been tested in humans in other medications without apparent safety issues, he said.

The research also found that the key reason the adjuvant-only vaccine worked was that it activated macrophages, immune cells that engulf and destroy foreign invaders. The researchers also observed other changes in the immune system, such as an increase in anti-inflammatory immune proteins called cytokines, and a decrease in pro-inflammatory cytokines. Though all the mechanisms aren't clear, this ratio has been linked to better survival after infection in previous studies, the researchers wrote.

In mice, the vaccine's protection persisted for 28 days.

Giving this vaccine to patients upon hospitalization or before outpatient surgery could reduce the rate of hospital-borne infections and help combat the problem of antibiotic resistance, study co-author Jun Yan, a doctoral student in microbiology at the University of Southern California.

"By reducing the infection rate in the hospital, we're also reducing the new emergence of antibiotic resistance, because we can also reduce the use of antibiotics in hospitals," Yan told Live Science.

Human testing is the next step. Other vaccines, such as the live tuberculosis vaccine, have long been known to trigger an innate immune response in addition to raising the body's guard against specific germs, Henao Tamayo, who studies those vaccines, told Live Science. But getting a nonspecific vaccine approved by the Food and Drug Administration (FDA) is new territory, Spellberg said. The research team is currently in talks with the FDA about what kind of testing would be needed, and they hope to begin clinical trials in 12 to 18 months.

"I think what they have already developed is highly promising," Henao Tamayo said, "and we could learn a lot from human studies."

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Vaccine for superbugs? New shot shows promise in early tests - Livescience.com

Novak Djokovic is already thinking about next season and his challenge to win the title of the Australian Open, which would put more distance between him and Rafael Nadal in the race for more 'Grand Slam'.

The world number one, in his latest interview for the CBS 60 Minutes programme, spoke of his refusal to be vaccinated against the coronavirus, which caused him to miss many tournaments, and made it clear that "people tried to brand me as anti-vaccine when I'm not. I am in favour of vaccines in the same way that I am in favour of freedom of choice.

Djokovic also spoke about his rivalry with Nadal and Roger Federer, with whom he formed the historic 'Big Three' of the sport: "I have enormous respect for them, that's what I can say. We are not friends because we are rivals and you can't share certain things that could go against you. I would love to be able to have dinner with Rafa and Roger in a while".

The 24-time major champion, who rested for a few days at his home in Marcella at the end of the Davis Cup finals in Malaga, will spend his pre-season in Dubai with his compatriot Hamad Medjedovic, the recent winner of the Next Gen Finals in Jeddah.

He will then travel to Riyadh (Saudi Arabia) to play an exhibition with Carlos Alcaraz on 27 December. It will be a technical stop on his way to Australia. He will play the United Cup in defence of Serbia. The venue for the Balkan team's matches will be Perth.

Djokovic will open on December 31 against China's Zhizhen Zhang.

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Novak Djokovic: People tried to label me as anti-vaccine and I'm for it - Marca

Boris Johnson

Covid inquiry expected to be told former PM was open to military options to obtain impounded jabs from factory in Leiden

Boris Johnsons appearance before the Covid-19 inquiry is not until Wednesday but it is already making headlines in the Netherlands amid a mixture of amusement and alarm at claims he asked for British spies to plan a raid on a Dutch vaccine plant.

The operation according to sources who briefed Johnsons employer, the Daily Mail would have taken place against the backdrop of a tit-for-tat row in March 2021 between the then prime minister and the EU, which was moving towards restricting exports of vaccines across the Channel.

An enraged Johnson asked security services to draw up military options to obtain impounded doses of AstraZeneca vaccine from a plant in Leiden after Britain had negotiated a deal with the company.

But while Britains security services were spared their biggest debacle on Dutch soil since Operation Market Garden, the claim has been widely reported on front pages in the Netherlands. Elsewhere, Russian state media generated a po-faced report on the claims, interspersing clips of Johnson with footage of British special forces and overlaying them with a sinister backing track.

The Dutch ministry of foreign affairs confirmed it was aware of the report but declined to comment.

Johnson is expected to refer to the episode, potentially in a written statement accompanying his evidence to the inquiry, which will take place over the course of Wednesday and Thursday.

Figures close to Johnson have been busily briefing the media before his appearance, advising that he will reject claims that he was not sufficiently engaged in policy during the 10-day period.

The former Conservative leader will reject claims that he did not concentrate on the looming threat of the pandemic during the half-term break in February 2020 because he was supposedly writing a biography about William Shakespeare.

A spokesperson for Johnson previously rejected reports that he was focused on the book during the critical period in question but Downing Street also did not deny that Johnson had worked on the book, for which he received a 88,000 advance from his publisher Hodder & Stoughton UK in 2015, since becoming prime minister in July 2019.

The evidence shows, from the diary extracts, that he wasnt away all the time. He came back into the office from Chevening. The records show he was working the whole time, he wasnt writing a book We think this one is quite easily dealt with. the Telegraph quoted a source close to Johnson as saying.

Johnson is expected to admit some fault when he is cross examined at the inquiry but will also seek to talk up the things that he believed he got right, ranging from the vaccines rollout to eventually opening up the economy.

He will argue that those criticising him have been doing so from specific perspectives including science, the economy and broader public health and that he was the only person who had to balance all of these things.

The former prime minister will resist going on the attack, according to his supporters, and will also seek to offer ideas about how the UK could cope with a future pandemic.

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Boris Johnson considered raid on vaccine plant in the Netherlands - The Guardian

A study billed as the last chance to develop an HIV vaccine this decade has been shut down, investigators announced Wednesday at a conference in Harare, Zimbabwe.

The trial, known as PrEPVacc, was testing two different vaccine regimens on about 1,500 volunteers in East and Southern Africa. After multiple other high-profile trials failed, a PrEPVacc investigator described the study this summer as the last roll of the dice for an HIV vaccine until the 2030s.

The study has now been halted early after an independent data monitoring committee concluded there was little or no chance the study would demonstrate efficacy, researchers told the International Conference on AIDS and STIs in Africa.

Although disappointing, the news may not surprise many HIV vaccine researchers. PrEPVacc was seen as a pioneering study, both as one of the first large, African-led HIV vaccine trials and one of the first trials to incorporate PrEP, the daily antiviral pills that can dramatically reduce the risk of HIV infection.

But the trial used older vaccine designs some scientists doubted would provide adequate protection.

With the failure, there are now no HIV vaccines being trialled for efficacy anywhere in the world, PrEPVacc investigator Pontiano Kaleebu said in a statement.

Efforts are limited to small, early-stage trials designed to test new technologies that might stand a chance against the wiliest virus humanity has ever encountered. Kaleebu said there now had to be greater urgency to push these technologies forward.

We have come so far in our HIV prevention journey, but we must look to a new generation of vaccine approaches and technology to take us forward again, he said. We must also look to a new generation of leaders. We set up PrEPVacc to grow our capacity in Africa to do future trials ourselves and to develop those who will lead them here in Africa.

The new strategies include sending HIV wanted posters to a specific set of immune cells by encoding them in another, more benign chronic virus. More popular is an approach called germline targeting, where researchers give a series of different jabs designed to nudge the immune system toward making the perfect, HIV-snaring antibodies.

Moderna, the National Institutes of Health, and IAVI (formerly known as the International AIDS Vaccine Initiative) have all invested in the latter.

Despite these results, IAVI remains optimistic that developing an HIV vaccine is possible, said IAVI CEO Mark Feinberg in an emailed statement. We believe that new approaches designed to induce broadly neutralizing antibodies to HIV are the most promising path forward.

Trial director Eugene Ruzagira said he hopes PrEPVacc data will eventually inform new efforts. Although no new volunteers will be dosed, researchers remain blinded to who is on which regimen and will continue following participants into next year. Afterward, theyll look at blood samples and data to try to decode precisely what went wrong.

The option of giving up the work is off the table, Ruzagira said. The work needs to continue.

Some researchers are skeptical, however, that the new technologies will ever lead to an HIV vaccine. Even as the HIV vaccine field has struggled for 40 years, companies have developed other methods of stopping transmission for extended periods: Forms of PrEP that can virtually eliminate the risk of infection with an injection every couple months. Biannual and annual injections are now in development.

Long-acting PrEP could raise the bar for how effective an HIV vaccine has to be, while also making it more difficult to run vaccine trials. Researchers, for example, may no longer be able to compare new shots to placebo.

PrEPVacc had been an early attempt to run a vaccine trial while also offering patients different forms of oral PrEP. And a portion of the study comparing two forms of oral PrEP will continue.

Longtime vaccine researchers say that even more outside-the-box trial designs may be needed for the next vaccine study, should one of the early stage projects prove promising.

Originally posted here:

Study billed as the last chance to soon develop an HIV vaccine fails - STAT

A man places a placard as he prepares a message during an HIV/AIDS awareness campaign on the eve of World AIDS Day in Kolkata, India, November 30, 2017. REUTERS/Rupak De Chowdhuri/ File photo Acquire Licensing Rights

KAMPALA, Dec 7 (Reuters) - A trial of an experimental HIV vaccine in Uganda, Tanzania and South Africa has been stopped early after preliminary data suggested it would not be effective in preventing infection, according to the trial's chief investigator.

The news is the latest blow to efforts to find an effective vaccine against a virus that has so far claimed about 40 million lives globally. Another 39 million are living with HIV, the majority of them in Africa.

The trial for the vaccine, part of a wider initiative called PrEPVacc, began in December 2020 with the enrolment of 1,512 healthy adults aged 18-40 and was due to end in 2024.

Pontiano Kaleebu, chief investigator for the programme, told Reuters on Thursday the programme's independent data and safety monitoring committee had "recommended that even if we continue we will not be able to show that the vaccine can be effective".

While there are drugs that can reduce the risk of getting HIV and treatments that can control the virus and prevent people from developing AIDS, the deadly immune condition resulting from untreated HIV, experts say an HIV vaccine would be an important tool in ending AIDS as a public health threat.

The trial, led by African researchers with support from various European institutions like Imperial College London, was testing two different combinations of experimental HIV vaccines.

It was also testing a new form of oral pre-exposure prophylaxis (PrEP), a drug that reduces the risk of getting HIV, to see if it was as effective as existing drugs. That part of the trial is ongoing.

Participants were mostly drawn from populations at high risk of infection like sex workers, gay men and fishermen.

A statement released on Wednesday by the vaccine trial programme said the failed trial, which was the only remaining active HIV vaccine efficacy trial in the world, underscored "how challenging it is to develop an effective HIV vaccine".

Researchers in South Africa terminated another trial in 2020 after tests of a vaccine in more than 5,000 people failed to show benefits.

Reporting by Elias Biryabarema and Jennifer Rigby Editing by Mark Potter

Our Standards: The Thomson Reuters Trust Principles.

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HIV vaccine trial in Africa halted after disappointing data - Reuters

Fair Access

African-led trial ended a year early as researchers conclude there is little or no chance new combination vaccines cut HIV risk

The first trial in Africa of two combination vaccines to prevent HIV has been halted after researchers concluded it was not working.

The vaccines (part of the PrEPVacc study) were being tested on 1,500 people aged between 18 and 40 in Uganda, Tanzania and South Africa.

The African-led trial, which began in December 2020, was stopped last month after an interim review of progress. The final results are expected to be made public in late 2024.

The trial of a pre-exposure prophylaxis pill running alongside the vaccines tests will continue.

Dr Eugene Ruzagira, trial director from the Uganda Virus Research Institute (UVRI) and assistant professor of epidemiology at the London School of Hygiene & Tropical Medicine, said: Vaccinations to PrEPVacc trial participants have been stopped because an analysis of the data collected so far by our independent data-monitoring committee has led them to conclude that there is little or no chance of demonstrating that the vaccines we are testing are reducing the risk of acquiring HIV.

The PrEPVacc trials, led by African researchers with support from European scientists, tested two different combinations of HIV vaccines to see if either could prevent infection in populations particularly at risk of infection. The trials were funded with a 15m (12.8m) grant from the EUs European & Developing Countries Clinical Trials Partnership.

Prof Jonathan Weber, from Imperial College London, one of the trials sponsors, said: We do clinical trials because we dont know the answer to questions. It was important to find out whether the combination vaccine regimens in PrEPVacc, developed over 20 years, should be ruled out or further developed for preventing HIV.

While we await the final results and analysis of individual products, I believe that our interim result puts this generation of putative HIV vaccines to bed, he said.

Previous trials in South Africa to test the only vaccine that had shown any success in protecting against HIV the RV144 developed in Thailand, was stopped in February 2020 after interim results found it was not working.

Prof Pontiano Kaleebu, PrEPVaccs chief investigator at UVRI, said developing an effective vaccine to prevent HIV infection was a critical goal for Africa.

He said: It is a goal that must have even greater urgency now that no HIV vaccines are being trialled for efficacy anywhere in the world.

We have come so far in our HIV-prevention journey, but we must look to a new generation of vaccine approaches and technology to take us forward again.

About 39 million people worldwide are living with HIV, more than 25 million in sub-Saharan Africa.

Ruzagira told an Aids conference in Zimbabwe on Wednesday that he remained optimistic. The scientific hurdles are high, but I have equally high hopes that an HIV vaccine will be developed one day, he said.

The RV144 vaccine was trialled in Thailand between 2003 and 2006, which after three years reduced infection rates by almost a third.

This article was amended on 8 December 2023 to clarify that the trials involved testing of two different combinations of HIV vaccines, not of HIV, as an earlier version said.

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HIV vaccine trial in Africa halted after disappointing initial results - The Guardian

(Precision Vaccinations News)

The Africa Centres for Disease Control and Prevention (Africa CDC) recently welcomed the announcement from The Global Vaccine Alliance (GAVI) Board for the establishment of the African Vaccine Manufacturing Accelerator (AVMA).

The AVMA is a financing mechanism to create a sustainable vaccine manufacturing industry in Africa. It will make up to $1 billion in funds available to support vaccine manufacturing in Africa.

Dr. Jean Kaseya, Africa CDC Director General, commented in a press release on December 8, 2023,"Today is a significant moment for Africa. The targeted USD 1 Billion from GAVI to African Manufacturers is a game changer for the continent and advances our efforts towards vaccine self-reliance."

"The African Union has set a target for the continent to produce 60% of the vaccines needed by 2040, and theAVMA is indeed an accelerator towards that ambition."

"GAVI has been an incredible partner in this; we will continue to advance together on this journey of self-reliance. Together, we are united with a mission for vaccine equity."

The launch of AVMA is an important message from our partners that Africa will no longer be solely a recipient of vaccines but an active member and contributor to the global vaccine ecosystem.

The collaboration has seen several vaccine manufacturing projects taking shape, and others are in the works to guarantee self-reliance in Africa should any health emergency or outbreak hit the continent.

In addition, Africa CDC remains committed to collaborating with all partners and stakeholders in the vaccine ecosystem to facilitate the full operationalization of AVMA and expedite the attainment of health security, as envisaged in Agenda 2063.

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$1 Billion Supports Vaccine Manufacturing in Africa Precision Vaccinations News - Precision Vaccinations

(Precision Vaccinations News)

The Coalition for Epidemic Preparedness Innovations (CEPI) recently announced it hadpartnered with Jurata Thin Film, Inc.to advance development of thermostable under-the-tonguevaccine films as a needle-free vaccine delivery platform.

On December 5, 2023, CEPI confirmed that it will provide up to an initial $1.2 million to support Jurata's proprietary innovative formulation platform, which, if shown to be successful, could help expand access to vaccines in underserved regions and advance the global response to future emerging infectious disease outbreaks.

CEPI's initial funding will support optimizing the composition and process of creatingthin films and preclinical studies.

Under the agreement with CEPI, Jurata will create vaccine films to remain stable at 2-8 degrees, 25 degrees, and 40 degrees.

Jurata will optimise the composition of the films by testing various buffers, pH, stabilizers, sugars, salts, and different drying parameters and assessing how this affects vaccine stability and delivery.

Jurata aims to improve vaccine accessibility by stabilizing the 3D structure of mRNA-containing lipid nanoparticle vaccine materials, provided by Quantoom Biosciences, part of Univercells, into a thin thermostable film, thereby removing frozen storage needs.

The vaccine films are also lightweight and compact, simplifying the transportation process and potentially allowing for more doses to be shipped at any one time compared to current needle-and-syringe distribution.

Dr. Irnela Bajrovic,Chief Scientific Officer, Jurata, commented in a press release, "Our stabilising formulations have the potential to facilitate global access to mRNA vaccines, and our thin film delivery platform could make vaccine administration far easier than needle-and-syringe injections."

"We are grateful to CEPI for supporting our innovative technology and look forward to working with Quantoom to show the breadth of mRNA vaccines our technology can stabilize and deliver."

This is the fourth partner to be announced as part ofCEPI's Call for Proposalsfor thermostable vaccine manufacturing innovations, announced in January 2022.

Thermostable vaccines are also identified as apreferred vaccine characteristicby the World Health Organization.

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$1.2 Million Supports Under-the-Tongue Vaccine Film Delivery - Precision Vaccinations

A new instrument has just been approved that could help catalyse the sustainable growth of vaccine manufacturing in Africa. The African Vaccine Manufacturing Accelerator (AVMA) is designed to make up to US$ 1 billion available over the next ten years to support the sustainable growth of Africa's manufacturing base, which has the potential to not only contribute to healthy global vaccine markets, but also benefit outbreak and pandemic prevention, preparedness, response and resilience.

The COVID-19 pandemic brought the strategic importance of access to vaccine manufacturing into the public eye and to the forefront of the minds of policymakers. The countries and regions with the strongest research, manufacturing and regulatory ecosystems were the first to access COVID-19 vaccines. Other regions, by stark contrast, were locked out of access during the early days of the pandemic, as vaccine nationalism and market failure initially held sway.

No region felt the negative effects of COVID-19 vaccine inequity more than Africa. And no region stands to benefit more from sustainable growth in its vaccine manufacturing sector.

At present, demand for vaccines in Africa is valued at over US$ 1 billion annually, with this figure projected to grow along with the continent's population over the next several decades. Africa already accounts for around 20% of the world's population, yet the continent's vaccine industry provides only around 0.2% of global supply.

A sustainable expansion of Africa's vaccine manufacturing capacity would have a double payoff for the continent, contributing to the growth of a high-value biotechnology sector on the continent at the same time as supporting pandemic and outbreak prevention and response. At the same time, a strong vaccine manufacturing sector in Africa could benefit the overall health of vaccine markets globally.

Speaking at the annual International Conference on Public Health in Africa in November 2023, Dr Jean Kaseya, director-general of the Africa Centres for Disease Control and Prevention (Africa CDC), likened this to the continent's 'second independence'. At the same event, Gavi interim CEO David Marlow signalled Gavi's commitment to work with partners to "drive an African vaccine revolution, creating an industry that can boost economies, create jobs and help ensure that when the next pandemic hits, vaccines made in Africa are ready to protect populations".

Since 2001, Gavi has become one of the world's largest buyers of vaccines, working closely with African countries and manufacturers to shape the market for vaccines, and helping to expand the number of manufacturers of Gavi-supported vaccines from 5 producers to 19. So when the African Union (AU) set a bold target for African countries to produce and supply more than 60% of the continent's vaccine requirements by 2040, Gavi was a natural partner to help chart a collective path towards a sustainable manufacturing ecosystem in the region.

Gavi's ten-point plan for developing and strengthening vaccine manufacturing in Africa set out the key actions needed to diversify and secure vaccine supply in Africa and support of the AU's vision, including the need for Gavi to update the Alliance's market shaping model to assign greater value to vaccine supply resilience in Africa.

As part of the ten-point plan, Gavi set out the need for a new financial instrument that would send a powerful signal to global markets that Gavi will support the development of African vaccine manufacturing. And this is where AVMA comes in. AVMA aims to deliver the right balance of incentives to encourage investment in Africa, and the entrance of new African manufacturers at the scale needed to be viable on a long-term basis.

The biotech sector in Africa is still young, and it will take time for new manufacturers to build the production scale required to be sustainable. AVMA works by offering two types of incentive payments that offset some of the initial high costs of production. Some of these payments will be higher for a subset of vaccines (the priority vaccine market group) for which there is an unmet need or a need to boost market health or for which a manufacturer has established a prioritised vaccine technology platform in Africa that could be brought online during a pandemic response.

The first type of payment, known as a 'milestone payment', will be triggered when a manufacturer producing one of the vaccines included in the Gavi priority vaccine market group succeeds in obtaining WHO prequalification (PQ). PQ is a form of regulatory approval that must be obtained before a manufacturer can win a Gavi-UNICEF tender . This payment is targeted to support manufacturers to offset some of the financial burden of meeting the standards for PQ, and helps to bridge the period between this prequalification and production.

Milestone payments are calibrated to provide the greatest incentive to invest in modes of manufacturing most likely to support pandemic preparedness. The highest milestone payments of US$ 25 million will accrue to manufacturers that receive prequalification for vaccines produced with a 'pandemic ready' technology platform, such as the capacity to produce mRNA or viral vector vaccines. At the other end of the scale, the lowest milestone payments of US$ 10 million will accrue to manufacturers that receive PQ for 'fill and finish' manufacturing of one of the vaccines in the priority market category , whereby the final stages of production, vial filling and labelling are undertaken at an African manufacturing facility.

The second type of payment, termed an 'accelerator payment', will be paid as a per-dose 'top-up', in addition to the offered market rate manufacturers receive on winning Gavi-UNICEF tenders. These payments will be highest, at around US$ 0.50 per dose, for the end-to-end manufacture of priority market vaccines , and vaccines produced using 'pandemic ready' technology platforms. At the other end of the scale, lower tiered incentives are paid for lower-cost 'fill and finish' manufacturing, with the overall objective to incentivise a more sustainable end-to-end business model.

AVMA will offer the highest per-dose incentive payments and milestone payment to manufacturers that are able to supply vaccines that have strategic importance for the African continent.

This strategic importance can derive from several factors, including the need to build supply security and resilience for vaccines against certain outbreak-prone diseases, specific opportunities for commercially sustainable new market entrants, or the need to develop and produce vaccines with product profiles optimised to meet African priorities and contexts.

The final list of priority market vaccines is designed to balance these strategic priorities, and ensure that incentives are calibrated to encourage a broad ecosystem without diluting their potential impact. The priority market vaccines are:

With an intended capitalisation of up to US$ 1 billion, AVMA is designed to provide incentives for ten years, with various caps on incentives so that no vaccine type, or single manufacturer, is overrepresented. In addition, the availability of incentives is balanced to offer the best chance of cultivating a broad and resilient manufacturing sector.

Detailed terms and conditions to underpin AVMA and the payment of incentives will be communicated prior to the launch of the facility.

AVMA is a clear signal that the political will to achieve the African Union's vision is now being translated into purposeful and pragmatic action.

The incentive structure for the AVMA was fine-tuned during an intense 12-month period of consultation, design and modelling. This extensive testing and calibration was done with the aim of ensuring that support would maximise the sustainability of African manufacturing capacity and minimise inadvertent market distortions. But building a thriving vaccine manufacturing ecosystem in Africa will take years of steady commitment, coordination and investment.

There are numerous initiatives aimed at strengthening vaccine manufacturing in Africa. Ensuring that this multitude of initiatives and national strategies are aligned will be crucial to developing a diverse ecosystem that meets Africa's strategic economic and pandemic preparedness goals. The speed at which manufacturers can achieve regulatory prequalification will also be a crucial rate-limiting step for the expansion of the sector.

Gavi estimates that AVMA would need to disburse between US$ 750 million to US$ 1 billion to see a solid and sustainable foundation offering both resilient vaccine supply and improved pandemic response. As a minimum, the instrument aims to support at least four African vaccine manufacturers operating sustainably and at scale to win Gavi/UNICEF tenders for the production of well over 800 million vaccine doses over 10 years.

The stage is now set for African vaccine manufacturing to be transformed in the years to come.

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The African Vaccine Manufacturing Accelerator: what is it and why is it important? - Gavi, the Vaccine Alliance

Clark, A. et al. Estimating global, regional and national rotavirus deaths in children aged <5years: Current approaches, new analyses and proposed improvements. PLoS ONE 12, e0183392 (2017).

Article PubMed PubMed Central Google Scholar

Troeger, C. et al. Rotavirus vaccination and the global burden of rotavirus diarrhea among children younger than 5 years. JAMA Pediatr. 172, 958965 (2018).

Article PubMed PubMed Central Google Scholar

Troeger, C. et al. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect. Dis 18, 12111228 (2018).

Article Google Scholar

Burnett, E., Jonesteller, C. L., Tate, J. E., Yen, C. & Parashar, U. D. Global impact of rotavirus vaccination on childhood hospitalizations and mortality from diarrhea. J. Infect. Dis. 215, 16661672 (2017).

Article PubMed Google Scholar

Parashar, U. D., Hummelman, E. G., Bresee, J. S., Miller, M. A. & Glass, R. I. Global illness and deaths caused by rotavirus disease in children. Emerg. Infect. Dis. 9, 565 (2003).

Article PubMed PubMed Central Google Scholar

WHO. Rotavirus vaccines: WHO position paperJuly 2021Vaccins antirotavirus: Note de synthse de lOMSJuillet 2021. Wkly. Epidemiol. Rec. Relev pidmiol. Hebd. 96, 301219 (2021).

Google Scholar

WHO. Rotavirus vaccines: WHO position paperJanuary 2013. Wkly. Epidemiol. Rec. Relev pidmiol. Hebd. 88, 4964 (2013).

Google Scholar

Carvalho, M. F. & Gill, D. Rotavirus vaccine efficacy: Current status and areas for improvement. Hum. Vaccines Immunother. https://doi.org/10.1080/21645515.2018.1520583 (2018).

Article Google Scholar

Platts-Mills, J. A. et al. Impact of rotavirus vaccine introduction and postintroduction etiology of diarrhea requiring hospital admission in Haydom, Tanzania, a rural African setting. Clin. Infect. Dis. 65, 11441151 (2017).

Article CAS PubMed PubMed Central Google Scholar

Mahamba, D. et al. Prevalence and factors associated with rotavirus infection among vaccinated children hospitalized for acute diarrhea in Mwanza City, Tanzania: A cross sectional study. Open J. Pediatr. 10, 392403 (2020).

Article CAS Google Scholar

Temu, A. et al. Prevalence and factors associated with Group A rotavirus infection among children with acute diarrhea in Mwanza, Tanzania. J. Infect. Dev. Ctries. 6, 508515 (2012).

Article PubMed Google Scholar

Jani, B. et al. Detection of rotavirus before and after monovalent rotavirus vaccine introduction and vaccine effectiveness among children in mainland Tanzania. Vaccine 36, 71497156 (2018).

Article PubMed Google Scholar

McNulty MS. Rotaviruses. J. Gen. Virol. 40(1), 18 (1978)

WHO. Manual of Rotavirus Detection and Characterization Methods (World Health Organization, 2009).

Google Scholar

Esona, M. D. & Gautam, R. Rotavirus. Clin. Lab. Med. 35, 363391 (2015).

Article PubMed Google Scholar

Santos, N. & Hoshino, Y. Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev. Med. Virol. 15, 2956 (2005).

Article PubMed Google Scholar

Malakalinga, J. J., Misinzo, G., Msalya, G. M. & Kazwala, R. R. Rotavirus burden, genetic diversity and impact of vaccine in children under five in Tanzania. Pathogens 8, 210 (2019).

Article CAS PubMed PubMed Central Google Scholar

Kirkwood, C. D., Boniface, K., Barnes, G. L. & Bishop, R. F. Distribution of rotavirus genotypes after introduction of rotavirus vaccines, Rotarix and RotaTeq, into the National Immunization Program of Australia. Pediatr. Infect. Dis. J. 30, S48S53 (2011).

Article PubMed Google Scholar

Roczo-Farkas, S. et al. The impact of rotavirus vaccines on genotype diversity: A comprehensive analysis of 2 decades of Australian surveillance data. J. Infect. Dis. 218, 546554 (2018).

Article PubMed Google Scholar

Mokomane, M. et al. Diversity of rotavirus strains circulating in Botswana before and after introduction of the monovalent rotavirus vaccine. Vaccine 37, 63246328 (2019).

Article CAS PubMed Google Scholar

Gibory, M. et al. Genetic diversity of rotavirus strains circulating in Norway before and after the introduction of rotavirus vaccination in children. J. Med. Virol. 94, 26242631 (2022).

Article CAS PubMed Google Scholar

Seheri, L. et al. Rotavirus strain diversity in Eastern and Southern African countries before and after vaccine introduction. Vaccine 36, 72227230 (2018).

Article CAS PubMed Google Scholar

Hokororo, A. et al. Predominance of rotavirus G1 [P8] genotype among under-five children with gastroenteritis in Mwanza, Tanzania. J. Trop. Pediatr. 60, 393396 (2014).

Article PubMed PubMed Central Google Scholar

Moyo, S. J. et al. Genetic diversity of circulating rotavirus strains in Tanzania prior to the introduction of vaccination. PLoS One 9, 10 (2014).

Article Google Scholar

WHO. Generic Portocols for (i) Hospital-Based Surveillance to Estimate the Burden of Rotavirus Gastroenteritis in Children and (ii) a Community-Based Survey on Utilization of Health Care Services for Gastroenteritis in Children: Field Test Version (World Health Organization, 2002).

Google Scholar

Akran, V. et al. Molecular characterization and genotyping of human rotavirus strains in Abidjan, Cote dIvoire. J. Infect. Dis. 202(1), 220224 (2010).

Article Google Scholar

Das, B. K. et al. Characterization of rotavirus strains from newborns in New Delhi, India. J. Clin. Microbiol. 32, 18201822 (1994).

Article CAS PubMed PubMed Central Google Scholar

Cunliffe, N. A. et al. Rotavirus G and P types in children with acute diarrhea in Blantyre, Malawi, from 1997 to 1998: Predominance of novel P [6] G8 strains. J. Med. Virol. 57, 308312 (1999).

Article CAS PubMed Google Scholar

Abeid, K. A. et al. Monovalent rotavirus vaccine effectiveness and impact on rotavirus hospitalizations in Zanzibar, Tanzania: Data from the first 3 years after introduction. J. Infect. Dis. 215, 8 (2017).

Google Scholar

ORyan, M. Rotarix(RIX4414): An oral human rotavirus vaccine. Expert Rev. Vaccines 6, 1119 (2007).

Article PubMed Google Scholar

Mchaile, D. N. et al. Prevalence and genotypes of Rotavirus among children under 5 years presenting with diarrhoea in Moshi, Tanzania: A hospital based cross sectional study. BMC Res. Notes 10, 6 (2017).

Article Google Scholar

Mhango, C. et al. Rotavirus genotypes in hospitalized children with acute gastroenteritis before and after rotavirus vaccine introduction in Blantyre, Malawi, 19972019. J. Infect. Dis. 15, 9 (2022).

Google Scholar

Ruiz-Palacios, G. M. et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N. Engl. J. Med. 354, 1122 (2006).

Article CAS PubMed Google Scholar

Yen, C. et al. Monovalent rotavirus vaccine provides protection against an emerging fully heterotypic G9P [4] rotavirus strain in Mexico. J. Infect. Dis. 204, 783786 (2011).

Article CAS PubMed Google Scholar

Correia, J. B. et al. Effectiveness of monovalent rotavirus vaccine (Rotarix) against severe diarrhea caused by serotypically unrelated G2P [4] strains in Brazil. J. Infect. Dis. 201, 6 (2010).

Article Google Scholar

Malakalinga, J. J., Misinzo, G., Msalya, G. M., Shayo, M. J. & Kazwala, R. R. Prevalence and genomic characterization of rotavirus group A genotypes in piglets from southern highlands and eastern Tanzania. Heliyon 8, e11750 (2022).

Article CAS PubMed PubMed Central Google Scholar

Steele, A. D. et al. Human rotavirus vaccine Rotarix provides protection against diverse circulating rotavirus strains in African infants: A randomized controlled trial. BMC Infect. Dis. 12, 8 (2012).

Article Google Scholar

Clarke, E. & Desselberger, U. Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings. Mucosal Immunol. 8, 117 (2015).

Article CAS PubMed Google Scholar

Svensson, L., Sheshberadaran, H., Vesikari, T., Norrby, E. & Wadell, G. Immune response to rotavirus polypeptides after vaccination with heterologous rotavirus vaccines (RIT 4237, RRV-1). J. Gen. Virol. 68, 19931999 (1987).

Article CAS PubMed Google Scholar

Sadiq, A. & Bostan, N. Comparative analysis of G1P [8] rotaviruses identified prior to vaccine implementation in Pakistan with Rotarix and RotaTeq vaccine strains. Front. Immunol. 11, 562282 (2020).

Article CAS PubMed PubMed Central Google Scholar

Ward, R. L. Possible mechanisms of protection elicited by candidate rotavirus vaccines as determined with the adult mouse model. Viral Immunol. 16, 1724 (2003).

Article CAS PubMed Google Scholar

Ianiro, G., Recanatini, C., DErrico, M. M., Monini, M., RotaNet-Italy Study Group. Uncommon G9P [4] group A rotavirus strains causing dehydrating diarrhea in young children in Italy. Infect. Genet. Evol. 64, 5764 (2018).

Article PubMed Google Scholar

Degiuseppe, J. I., Stupka, J. A. & Network, A. R. S. Emergence of unusual rotavirus G9P [4] and G8P [8] strains during post vaccination surveillance in Argentina, 20172018. Infect. Genet. Evol. 93, 104940 (2021).

Article CAS PubMed Google Scholar

Tatte, V. S., Maran, D., Walimbe, A. M. & Gopalkrishna, V. Rotavirus G9P [4], G9P [6] and G1P [6] strains isolated from children with acute gastroenteritis in Pune, western India, 20132015: evidence for recombination in genes encoding VP3, VP4 and NSP1. J. Gen. Virol. 100, 16051630 (2019).

Article CAS PubMed Google Scholar

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