Category: Vaccines

Mechanism Behind AstraZeneca and J&J Vaccine Blood Clots Found

A cloud of platelet factor 4 proteins interacting with the electrostatic surface of the Oxford vaccine, as seen through the computational microscope.
Credit: Chun Kit Chan, Arizona State University

An international team of scientists believe they may have found a molecular mechanism behind the extremely rare blood clots linked to adenovirus vaccines.

Scientists led by a team from Arizona State University, Cardiff University and others worked with AstraZeneca to investigate vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome (TTS), a life-threatening condition seen in a very small number of people after receiving the Oxford-AstraZeneca or Johnson & Johnson vaccines.

“The mechanism which results in this condition, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), was unknown,” said Abhishek Singharoy, an Arizona State University scientist and corresponding author of the study who teamed up to lead an international effort to tease out the details. 

Together, the team worked to solve the structural biology of the vaccine, and see the molecular details that may be at play, utilising state-of-the cryo-EM technology to analyse the AstraZeneca vaccine in minute detail. They sought to understand whether the ultra-rare side effect could be linked to the viral vector which is used in many vaccines, including those from Oxford/AstraZeneca and Johnson & Johnson.

Their findings suggest it is the viral vector – in this case, an adenovirus used to shuttle the coronavirus’ genetic material into cells – and the way it binds to platelet factor 4 (PF4) once injected that could be the potential mechanism.

In very rare cases, the scientists suggest, the viral vector may enter the bloodstream and bind to PF4, where the immune system then views this complex as foreign. They believe this misplaced immunity could result in the release of antibodies against PF4, which bind to and activate platelets, leading to clustering and blood clotting.

“It’s really critical to fully investigate the vector-host interactions of the vaccine at a mechanistic level,” said Singharoy. “This will assist in understanding both how the vaccine generates immunity, and how it may lead to any rare adverse events, such as VITT.”

Their findings were published in Science Advances.

Adenovirus expert Professor Alan Parker said: “VITT only happens in extremely rare cases because a chain of complex events needs to take place to trigger this ultra-rare side effect. Our data confirms PF4 can bind to adenoviruses, an important step in unravelling the mechanism underlying VITT. Establishing a mechanism could help to prevent and treat this disorder.”

“We hope our findings can be used to better understand the rare side effects of these new vaccines – and potentially to design new and improved vaccines to turn the tide on this global pandemic.”

The AstraZeneca and Johnson & Johnson vaccines both use an adenovirus to carry SARS-CoV-2 Spike proteins to trigger an immune response.

Since VITT was seen in both vaccines, scientists wondered whether the viral vector was involved. Additionally, neither the Moderna nor Pfizer vaccines, both mRNA vaccines, showed this effect.

Using cryo-EM technology to flash-freeze preparations of ChAdOx1, the adenovirus used in the AstraZeneca vaccine, they produce microscopic images of the vaccine components.

They were then able to view the viral capsid structure and other critical proteins that allow entry of the virus into the cell.

In particular, the team outlined the details for the structure and receptor of ChAdOx1, which is adapted from chimpanzee adenovirus Y25 – and how it interacts with PF4. They believe it is this specific interaction – and how it is then presented to the immune system – that could cuase the immune system to see it as foreign and release antibodies against this self-protein.

The research team also used computational models to show that one of the ways the two molecules tightly bind is via electrostatic interactions. The group showed that ChAdOx1 is mostly electronegative, attracting other positively charged molecules to its surface.

First author Dr Alexander Baker said: “We found that ChAdOx1 has a strong negative charge. This means the viral vector can act like a magnet and attract proteins with the opposite, positive charge, like PF4.” Baker is a member of ASU’s Biodesign Center for Applied Structural Discovery and an Honorary Research Fellow at Cardiff University School of Medicine.

“We then found that PF4 is just the right size and shape that when it gets close to ChAdOx1 it could bind in between the negatively charged parts of ChAdOx1’s surface, called hexons.”

The research team are hopeful that armed with a better understanding of what may be causing rare VITT they can provide further insights into how vaccines and other therapies, which rely on the same technology, might be altered in the development of the next generation vaccines and therapies.

“With a better understanding of the mechanism by which PF4 and adenoviruses interact there is an opportunity to engineer the shell of the vaccine, the capsid, to prevent this interaction with PF4. Modifying ChAdOx1 to reduce the negative charge may reduce the chance of causing thrombosis with thrombocytopenia syndrome,” said Baker.

The team likened it to the ‘two birds, one stone’ effect. The key contacts of individual amino acids that are essential to the capsid protein’s proteins interaction with PF4 can removed or substituted.

“The modification of the ChAdOx1 hexons to reduce their electronegativity may solve two problems simultaneously: reduce the propensity to cause VITT to even lower levels, and reduce the levels of pre-existing immunity, thus helping to maximize the opportunity to induce robust immune responses, said Singharoy.”

Source: EurekAlert!

WHO Predicts Shortfall in Syringe Production

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The World Health Organization has said that with the goal of two COVID vaccine doses for seven billion people between now and 2023, a shortage of at least one billion syringes “could occur”, if manufacturing does not increase. This could endanger other immunisation programmes.

Lisa Hedman, WHO Senior Advisor, from the Access to Medicines and Health Products division, warned that there could be a generation of children who miss scheduled immunisation jabs unless manufacturers come up with a way to make more single-use disposable syringes.

“When you think about the magnitude of the number of injections being given to respond to the pandemic, this is not a place where we can afford shortcuts, shortages or anything short of full safety for patients and healthcare staff,” said the WHO expert.

She told media that more than 6.8 billion doses of COVID vaccines are being administered globally per year – nearly twice the yearly number for routine inoculations.

“A shortage of syringes is unfortunately a real possibility and here’s some more numbers. That [given] the global manufacturing capacity of around six billion a year for immunisation syringes it’s pretty clear that a deficit in 2022 of over a billion could happen if we continue with business as usual.”

Reuse of syringes was inadvisable, also noting that syringes were particularly prone to transport delays because they took up 10 times the space of a vaccine.

Meanwhile, the heads of the International Monetary Fund (IMF), World Bank Group, WHO and the World Trade Organization (WTO) held a follow up session of High-Level Consultations with the CEOs of leading COVID vaccine manufacturing companies on Tuesday.

All participants at the meeting agreed on the urgency of increased vaccine dose delivery to low-income countries, where less than 2.5% of the population has been fully vaccinated.

The meeting’s aim was to identify how to ensure more equitable distribution of vaccines and all participants pledged to continue working together to clarify donations, vaccine swaps and delivery schedules, so that distribution of the life-saving vaccines can be more effectively targeted towards needy countries.

The meeting of the Multilateral Leaders Task Force on COVID-19 built on technical work undertaken by multidisciplinary teams during the months of September and October.

During the consultations, the leaders of the four organisations and the CEOs also examined how best to tackle trade-related bottlenecks; how to improve the donation process; what additional steps are needed to reach the vaccination target of 40% of people in all countries by the end of the year; and how to improve transparency and data sharing with the IMF-WHO Vaccine Supply Forecast Dashboard and the Multilateral Leaders Task Force.

The effort will require close collaboration between manufacturers, governments and the international COVAX initiative, on enhanced delivery schedules, especially for doses that are being donated.

Source: UN News

UN Urges Group B Streptococcus Vaccine to Protect Babies

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There is an urgent need for vaccines against Group B streptococcus, a major cause of preterm births, disability and infant mortality worldwide, according to a UN-backed report published on Wednesday.

Group B streptococcus (GBS) is a gram-positive bacteria that colonises the gastrointestinal and genitourinary tract. It can be transmitted in utero, is linked to around 150 000 infant deaths each year, more than half a million preterm births and significant long-term disability.

The report by the World Health Organization (WHO) and the London School of Hygiene & Tropical Medicine (LSHTM) updates 2017 estimates, and reveals that the global burden of GBS is far higher than was previously recognised.

“This new research shows that Group B strep is a major and underappreciated threat to newborn survival and wellbeing, bringing devastating impacts for so many families globally,” said Dr Phillipp Lambach, Medical Officer from WHO’s Immunization, Vaccines and Biologicals department.

The report is the first to quantify the major contribution of GBS to preterm births, and to neurological impairments such as cerebral palsy, hearing and vision loss, that can occur following infection.

Around 15% of all pregnant women worldwide, nearly 20 million annually, carry the GBS bacterium in their vagina, which can then spread to a foetus, or to newborns during labour. At present, GBS disease prevention in newborns is by administering antibiotic prophylaxis to women during labour, if the bacterium is detected during pregnancy.

However, significant health risks remain, as this intervention is unlikely to prevent most GBS-associated stillbirths, preterm births, or GBS disease that occurs later after birth.

“It is difficult to describe the breadth or depth of the grief when your child dies, or the accompanying guilt, and how it changes you, your family, and your relationships forever,” said Debbie Forwood, whose daughter Ada was stillborn after she developed a GBS infection.

Vaccine development urged
GBS burden is highest in low and middle-income countries, where screening and treatment are most challenging to implement, with regions such as sub-Saharan Africa having the highest rates of maternal GBS.
Now is the time for action, said Joy Lawn, an LSHTM Professor who contributed to the report.  While several candidate GBS vaccines are in development, none are yet available despite decades in the pipeline. The report calls for stepping up development of an effective GBS vaccine that could be administered to expectant mothers during routine pregnancy checkups.

The partners estimate more than 50 000 GBS-related deaths, and over 170 000 pre-term births, could be avoided if over 70 per cent of pregnant women were vaccinated.

Such protection could also be highly cost-effective, they added.  Net benefits from a year of maternal vaccinations could reach as high as $17 billion, accruing over several years, provided doses are affordably priced. For Ms. Forwood, this would be a bittersweet development.

“Only a GBS vaccine could have saved Ada.  When a vaccine can be widely rolled out, I will weep and scream with the unfairness that it came too late for her, and for all the other babies who are needlessly suffering and dying every year that it is delayed,” she said.

“But I will also weep with joy that in the future, many more will live, and their families will be saved from the living hell that is the death of a child.”

Source: UN News

Vaccine to Prevent Hookworm Infection Could be a ‘Gamechanger’

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There’s been a significant breakthrough in the development of a vaccine to prevent hookworm infection – a parasite which causes serious disease in tens of millions of people globally.

Mouse trials of the vaccine candidate in mice indicate that it is more than twice as effective than current alternatives. The results were published in Vaccines.

Professor Istvan Toth from UQ’s School of Chemistry and Molecular Biology said the easy oral administration would be a gamechanger for developing countries.

“Our vaccine candidate can be orally self-administered, bypassing the need for trained medical staff, and means there’s no requirement for special storage, enabling it to reach large, isolated populations,” Professor Toth said, noting that costs can be significantly reduced.

A serious healthcare challenge
About 500 million people worldwide are infected with hookworm, which lives within the human intestine, feeding on the host’s blood, digested through a special set of enzymes.

It’s often found in regions with poor water quality, sanitation, and hygiene – greatly impacting on the physical and cognitive development of children and increasing the risk of mortality and miscarriage.

UQ’s trials in mice showed significant improvements on an alternative vaccine candidate which only achieved a 30 to 50 per cent reduction in the number of worms.

“The UQ-developed vaccine resulted in an impressive 94% worm reduction in mice,” Professor Toth said, noting that besides being easier to deliver, it “triggers a staggeringly good immune response.”

Hookworms lose their appetite
Paper co-author Dr Mariusz Skwarczynski said the hookworm’s digestion enzyme (APR 1) was the target.

“When the function of these enzymes is blocked, the parasite starves,” Dr Skwarczynski said.

“Our vaccine produces antibodies against the hookworm enzymes responsible for the digestion of blood – they simply stop being able to eat properly.”

The researchers plan to continue working on and refining the vaccine candidate in preclinical development settings, to ensure its safety and efficacy, before beginning human clinical trials.

Source: University of Queensland

Creating a Cross-protective Coronavirus Vaccine

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Researchers have found that by targeting the core region of the spike protein receptor-binding domain, which remains structurally similar among SARS-related viruses, they can create a vaccine that offers cross-protection against SARS coronaviruses.

The COVID pandemic, caused by the β-coronavirus SARS-CoV-2, alerted the world to the seriousness of the threat posed by novel viruses. To protect against similar future outbreaks, there is an urgent need for broadly protective vaccines against SARS-related coronaviruses. In a recent study published in Journal of Experimental Medicine, a team of researchers led by Osaka University generated an immune antigen that was based on a conserved protein on the surface of SARS-related viruses. In mice immunised with this antigen, cross-neutralising antibodies against SARS-related viruses were elicited.

The coronavirus spike protein, specifically the receptor-binding domain (RBD) of spike protein that enables the virus to attach to host cells is a target for the development of neutralising antibodies, and a promising vaccine candidate. The RBD is made of two regions: the head, which is more immune-reactive and so has the most antibodies created for it, and the core. The head however changes more rapidly, while the core region is more stable amongst SARS-related viruses. Antibodies raised against this conserved core region of the RBD can therefore generate cross-protection against multiple SARS-related viruses.

As lead authors Ryo Shinnakasu and Shuhei Sakakibara explained, “The key to generating a vaccine that offers broad cross-protection among related viruses is to target a structure on the viral surface that is highly conserved. Our approach was to generate a vaccine in which the non-conserved region was masked from the immune system by the introduction of a carbohydrate molecule (or glycan) by a method known as glycan engineering. This would in turn expose the conserved core region of the RBD of spike protein.” When used to immunise mice, protective antibodies were induced that recognised the RBD core region not only of SARS-CoV-2 but also of other SARS-related viruses, such as bat SARS-like coronavirus, WIV1-CoV.

This finding is particularly promising because it demonstrates the potential for highly protective vaccines against various SARS-related viruses. As senior author Tomohiro Kurosaki warned, “Despite the existence of effective vaccines against current viruses, there is potential for the emergence of similar viruses in the future. This highlights the real need for broadly protective vaccines against SARS-related coronaviruses.”

The novel approach of vaccine design that they describe may help protect against a future global health crisis such as that experienced during the COVID pandemic.

Source: Osaka University

Typhoid Vaccine Safe for Children in Sub-Saharan Africa

Source: Pixabay CC0

typhoid vaccine has proven to be safe and effective for children, which raises hope of fighting the disease in Sub-Saharan Africa, according to a new study conducted in Malawi.

There are more than 1.2 million typhoid cases and 18 703 deaths per year in the region, the researchers wrote. The World Health Organization (WHO) recommended the typhoid conjugate vaccine in 2018 for use in countries where the disease is endemic.

Clinical trials in Malawi showed that a single dose of typhoid conjugate vaccine (the only one licensed for children as young as six months) prevented typhoid in roughly 84% of 14 069 children aged 9 months to 12 years.

“It is a great result for Malawi and for Africa,” says study co-author Melita Gordon, professor of clinical infection, microbiology and immunology at the University of Liverpool and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.

“We were the only site chosen for the trial on the continent. The other sites were in Nepal and Bangladesh and the results were completely consistent across the three sites.”

Typhoid is endemic in Malawi, which records 400 to 500 cases per 100 000 every year, according to Queen Dube, chief of health services at Malawi’s Ministry of Health.

While typhoid is treatable, it can impair physical and cognitive development in children, affect school attendance and performance, limit productivity and reduce earning potential.

“The existing vaccine could not be used in very young children. In addition, the first line antibiotics have been found to be ineffective against multi-drug resistant strains,” Prof Gordon said. “With this vaccine, we can now expect a reduced typhoid burden.”

After 18 to 24 months of surveillance, the vaccine was found to be safe, with no serious adverse effects on children. It also worked equally well on pre-school aged children.

Prof Gordon explains that the study encountered challenges such as a few children moving out of the research sites within the study period, and COVID-19 forced them to suspend the study for two months.

“However, we eventually managed a good retention rate due to regular text messaging to parents and the hard work of health surveillance assistants in mobilisation activities,” she added.

The efficacy data of the typhoid conjugate vaccine is the first in Africa, according to Gordon, who hopes that other African countries will follow Malawi’s example in planning to roll out the vaccine.

Source: SciDev.Net

Good Uptake of Flu Jabs for Children in Procedures

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Offering an influenza vaccination to children about to have surgery and general anaesthesia  at a US children’s hospital resulted in a great increase in flu vaccinations there. In their findings presented at the ANESTHESIOLOGY® 2021 annual meeting, the researchers also posited that this raised vaccination awareness.

“The ongoing threat of a simultaneous COVID pandemic and seasonal flu epidemic makes the widespread use of flu vaccines more important than ever,” said Tyler Morrissey, MD, lead author of the study and assistant professor of pediatric anesthesiology, Department of Anesthesiology, University of Colorado School of Medicine, Aurora. “Our research shows that having a standardised process for getting children vaccinated for flu while under anaesthesia during surgery provides a ‘teachable moment’ and opportunity to educate families on the importance of flu vaccination, and may be a model for other childhood vaccinations while under anaesthesia, including the COVID vaccine.”

Epidemics of seasonal flu occur annually. Although the CDC recommends that everyone 6 months and older receive a yearly flu vaccine, during the 2019-20 flu season, the authors noted that vaccination rates were less than 50% for adults and 60% for children.

In the study, the authors hypothesised that the perioperative period when patients are undergoing anaesthesia for surgery would be a ‘teachable moment’ for flu vaccination, which they defined as an event motivating individuals to spontaneously adopt risk-reducing health behaviours.

In October 2020, a standardised ‘Best Practice Alert’ process was implemented to actively offer flu vaccinations to all paediatric patients having general anaesthesia at the hospital In the preanaesthetic area, a care team member received a computer alert then determined if the child was eligible, discussed vaccination benefits and obtained parental consent for the vaccine. The vaccine was then administered in the operating room (OR) after the induction of general anaesthesia. Prior to the 2020-21 season, flu vaccinations under anaesthesia were only offered upon patient or family request.

The researchers found the number of children receiving perioperative flu vaccinations increased by 3500% after implementation of the institution’s standardised protocol, compared to the previous year. During the 2019-20 flu season, only 30 perioperative vaccines were administered. Prior to the intervention during the 2020-21 flu season, only 30 vaccines were given over a six-week period (1 Sept.–16 Oct.).  However, after the intervention that same season, 1063 flu vaccines were administered over a 25-week period (16 Oct.–31 March), with no reported vaccine-related complications.
“We’re super encouraged to see so many parents agree to have their children vaccinated for flu while undergoing anaesthesia,” said Dr. Morrissey. “The CDC has recommended that flu vaccination be offered to children 6 months of age and older at every health care seeking opportunity. As physicians on the front lines of the COVID pandemic, this is another great opportunity for our specialty to make a significant impact on public health.” 

Source: American Society of Anesthesiologists

World-first Malaria Vaccine Receives WHO Recommendation

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The World Health Organization (WHO) is recommending widespread use of a new malaria vaccine among children in sub-Saharan Africa and in other regions with moderate to high P. falciparum malaria transmission. The vaccine, known as the RTS,S/AS01 (RTS,S or Mosquirix), has been trialled in three countries in a pilot programme involving 800 000 children.

Though the vaccine only offers moderate protection against malaria, with 36% protection against malaria cases among children. One study estimated that even with realistic vaccine coverage, at a constraint of 30 million doses, 5.3 million cases and 24 000 deaths could be prevented among children under five, .

“This is a historic moment. The long-awaited malaria vaccine for children is a breakthrough for science, child health and malaria control,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “Using this vaccine on top of existing tools to prevent malaria could save tens of thousands of young lives each year.”

This comes amid stagnation in progress in recent years against the deadly disease. In sub-Saharan Africa, malaria remains a primary cause of childhood illness and death. More than 260 000 African children under the age of five die from malaria annually.

“For centuries, malaria has stalked sub-Saharan Africa, causing immense personal suffering,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “We have long hoped for an effective malaria vaccine and now for the first time ever, we have such a vaccine recommended for widespread use. Today’s recommendation offers a glimmer of hope for the continent which shoulders the heaviest burden of the disease and we expect many more African children to be protected from malaria and grow into healthy adults.”

The WHO recommends that in the context of comprehensive malaria control the RTS,S malaria vaccine be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by the WHO. This vaccine should be provided in a schedule of 4 doses in children from 5 months of age for the reduction of malaria disease and burden.

The outcome of the pilots informed the recommendation based on data and insights generated from two years of vaccination in child health clinics in Ghana, Kenya and Malawi. Findings include:

  • Vaccine introduction is feasible, improves health and saves lives, with good and equitable coverage of RTS,S seen through routine immunization systems. This occurred even in the context of the COVID pandemic.
  • RTS,S enhances equity in access to malaria prevention.
  • Data from the pilot programme showed that more than two-thirds of children in the 3 countries who are not sleeping under a bednet are benefitting from the RTS,S vaccine.
  • Layering of tools results in over 90% of children benefitting from at least one preventive intervention (insecticide treated bednets or the malaria vaccine).
  • Strong safety profile: To date, more than 2.3 million doses of the vaccine have been administered in 3 African countries – the vaccine has a favorable safety profile.
  • No negative impact on uptake of bednets, other childhood vaccinations, or health seeking behavior for febrile illness. In areas where the vaccine has been introduced, there has been no decrease in the use of insecticide-treated nets, uptake of other childhood vaccinations or health seeking behavior for febrile illness.
  • High impact in real-life childhood vaccination settings: Significant reduction (30%) in deadly severe malaria, even when introduced in areas where insecticide-treated nets are widely used and there is good access to diagnosis and treatment.
  • Highly cost-effective: Modelling estimates that the vaccine is cost effective in areas of moderate to high malaria transmission.

Next steps for the WHO-recommended malaria vaccine will include funding decisions from the global health community for broader rollout, and country decision-making on whether to adopt the vaccine as part of national malaria control strategies.

The pilot programme was financed through collaboration between Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

Source: WHO

Are Combination COVID Vaccines the Wave of the Future?

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An article in MedPage Today examines the potential for combination COVID vaccines.

Novavax and Moderna have recently announced the development of combination vaccines that would protect not only against COVID, but also against influenza. In the case of Moderna, they are testing a combination vaccine that also includes protection against respiratory syncytial virus (RSV) — a viral illness for which no vaccine is currently available, which would be a major advancement Because COVID vaccines can be administered simultaneously with other vaccines, albeit in separate injections, the next step would be to co-formulate them in the same injection with other vaccinations.

Combination vaccines are extremely valuable for several reasons, chief among them is convenience. If, during one visit to a provider, a person can get multiple vaccinations, it ensures uptake of all those vaccines without the need to schedule multiple visits or use multiple injections. A single needle puncture is better than multiple punctures, even for those who are not needle phobic. As more vaccines are developed, combination vaccines become critical in getting doses into arms with the minimum number of injections.

Combination vaccines have been around for a long time, and are the mainstay of routine vaccination. Today, children receive several combination vaccinations including the well-known MMR (measles, mumps, rubella) and DTap (diphtheria, tetanus, acellular pertussis). These types of vaccines have a long history with DTP, the first combination vaccine used in humans, dating to the 1940s. Pentacel immunises against five different pathogens at once. Such convenience, especially with hard-to-reach populations, is invaluable. Adults also receive combination vaccinations, most prominently the Tdap (tetanus, diphtheria, acellular pertussis) boosters. Many physicians wish there were more combination vaccination products available because they have the potential to significantly increase vaccination rates.

It is of course necessary to determine that combination vaccines are safe and effective. Because they contain more antigen, reactions at injection sites might be more pronounced, fever might be slightly higher, and tolerability lower. To avoid the risk of febrile seizures, infants do not get the MMRV (measles, mumps, rubella, varicella) vaccine, instead getting varicella separately.
A combination vaccine’s components should not interfere with each other or blunt the immune response. This immune interference was a concern with vaccines combining Hib with DTap. For instance, vaccines with different storage conditions or delivery mechanisms (eg, subcutaneous vs intra-muscular; lipid nanoparticle encased) may not be the best candidates to combine. It is also important to combine vaccines that have compatible age or time-based schedules for administration.

As scientists explore a combination flu and COVID vaccine, they will be looking closely at all of these safety and efficacy considerations.

It’s important to emphasize, considering widespread disinformation from the anti-vaccine movement, that there is no “antigen overload” risk with combination vaccines. The human immune system is bombarded with antigens every day. We even become bacteremic, when we brush our teeth, or eat. The antigens contained in a combination vaccine are miniscule by comparison. In fact, the first ever vaccine, for smallpox, was packed with particles and impurities but was still incredibly efficacious and led to control and eventual elimination of one of humanity’s deadliest scourges.

It is likely to see individual attacks on COVID combination vaccines long before they are even available. We’ve previously seen such attacks on the MMR vaccine — these attacks became so pervasive that manufacturers started to produce the single vaccines again to placate people who were the victims of a concerted disinformation campaign. But we can learn from these past challenges. It will be important to fight disinformation about the COVID-19 combination vaccines early on, and encourage their uptake when they become available.

But one thing is certain: we should aim to make COVID vaccination convenient, normal, and easy. Proactively working on next generation vaccines that do this by combining with other vaccinations, altering the mode of delivery (eg, oral or nasal vaccines), or simplifying storage requirements are important tasks.

Source: MedPage Today

Attenuated Virus Confers Broader Flu Protection

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A mouse study using both attenuated and inactivated forms of influenza has helped explain why people vaccinated with the inactivated virus still occasionally end up contracting the illness. The finding should help researchers develop vaccines that offer broad protection against viruses.

Influenza is a major global health burden, with the World Health Organization estimating that it causes one billion cases annually. Each year, vaccines are developed that offer some protection against infection. But the influenza virus is a moving target that is constantly mutating, and so vaccines can lose their effectiveness as a season progresses.

Influenza vaccines commonly come in two forms: inactivated vaccines (including component vaccines) and live attenuated vaccines. Live vaccines confer broader protection against variants than inactivated vaccines, but side effects such as fevers and headaches are more common. A result they have yet to be approved in some countries. Live vaccines induce the production of broadly reactive antibodies, but until now, scientists didn’t know why.

In a recent study, Masato Kubo of the RIKEN Center for Integrative Medical Sciences and his co-workers have discovered two processes that live vaccines induce in mice that together account for their broader protection.

They found that, like the virus itself, the live vaccine virus causes the virus to replicate deep in the lungs, which in turn induces a structural change in the virus haemagglutinin, a mushroom-shaped protein on the surface of the virus involved in infecting cells. This structural change exposes previously hidden regions of antigens that the immune system can recognise.

Next, germinal cells are activated by interleukin 4 (IL-4), a cytokine heavily involved in regulating antibody production. IL-4 is derived from special T cells known as follicular helper T cells. This activation causes a minor population of B cells to proliferate and it is these B cells that are responsible for generating broadly protective antibodies.

The role of IL-4 in inducing the broad immune response came as a surprise. “Until now there had been no direct evidence to show the importance of IL-4,” says Kubo. “That was one of the surprises of this study for me.”

“We believe both processes are needed for generating broadly active antibodies: viral duplication in the lungs and expansion of the minor population of B cells,” says Kubo. “These two processes mostly likely occur when a person is infected by the influenza virus itself.”

The team now plans to see if there are similar mechanisms for other viruses such as SARS-CoV-2.

Source: RIKEN