Category: Flu Virus

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Getting a Grip on Influenza: The Pursuit of a Universal Vaccine (Part 3) – Forbes

August 30, 2022

Employees in cleanroom suits test the procedures for the manufacturing of the messenger RNA (mRNA) ... [+] for the Covid-19 vaccine at the new manufacturing site of German company BioNTech on March 27, 2021 in Marburg, central Germany. (Photo by Thomas Lohnes / AFP) (Photo by THOMAS LOHNES/AFP via Getty Images)

This is a short series about a recent breakthrough on the road to developing a much sought-after broadly neutralizing vaccine against all influenza A viruses. If successful, it may act as a precursor to a truly universal flu vaccine, one that protects against all types, subtypes, and lineages of the virus. The breakthrough may also provide a blueprint for developing a Covid-19 vaccine that retains its efficacy in the face of new variants.

In the first part of this series, I gave a brief overview of the history and nature of influenza viruses, including why it has been so difficult to develop successful vaccines. Here, and in the previous article, I discuss some of the attempts that have been made to overcome these challenges, including their shortcomings. And in the last few installments I will offer a detailed analysis of the latest and most promising advances in the field.

Understanding mRNA Technology

Traditional influenza vaccines are based on killed influenza viruses. Inactivated viruses cannot cause infection or disease, but when injected they rally our immune system into action all the same. While our immune system clears the viruses, it learns about them. Next time were exposed, it is already primed to defend against infection.

But there are a couple issues with influenza vaccines that rely on inactivated viruses. For one, they take a long time to produce. Candidate vaccine viruses need to be grown, either in fertilized hens eggs or in mammalian cells, before being inactivated and purified for use in vaccines this is a biological production process, and can take up to six months to complete. This means the wild type viruses circulating across the globe can continue to mutate while the vaccines are being made. If the viruses change enough, they may be able to evade the immunological memory the vaccines would provide us. Slow production times also render inactivated vaccines poorly suited to pandemic response, where speed is of the essence.

Enter messenger RNA (mRNA) technology. Unlike traditional flu vaccines, mRNA vaccines do not depend on the cultivation of viruses. Instead, they are based on the synthesis of carefully designed mRNA.

All of the cells in the human body contain proteins. These are the building blocks of life, involved in almost all of our bodys vital processes. Messenger RNA, in turn, is crucial to the synthesis of proteins. Our cells need instructions to build proteins, and mRNA provides these instructions in the form of genetic information. In a sense, mRNA acts as a kind of blueprint.

Vaccines can take advantage of this, using mRNA to instruct our cells how to produce a protein or even just a small section of a protein that is unique to whatever virus the vaccines are meant to protect us from. In the case of Covid-19, for example, vaccines include mRNA that teaches our cells to make the SARS-CoV-2 spike protein, which the virus uses to bind to our cells. Our immune system then recognizes these proteins as foreign entities and quickly gets to work, as it would against inactivated viruses or the wild-type virus itself.

Lightning Fast Manufacturing

Messenger RNA vaccines can be manufactured extremely quickly because they bypass the need for inactivated viruses or virus antigens. Unlike traditional vaccines, mRNA vaccines are synthesized chemically. The process is more akin to how a pharmaceutical drug like aspirin is produced than it is to how current flu shots are produced.

As soon as researchers have a complete sequence of a virus genome, they can isolate the section they want to use for vaccination usually, the gene corresponding to the surface protein the virus uses to bind and enter our cells and artificially synthesize it in the lab. The gene can then be inserted into a small, circular piece of DNA known as a plasmid. Plasmids are easy to replicate, allowing researchers to produce large amounts of the target viral gene at once. Finally, the plasmids are put into a reactor with a molecule that transcribes the viral RNA into mRNA. Any remaining plasmid material is broken down and the mRNA put through a series of purifiers before being packaged into the protective lipid shell. The whole process takes a matter of weeks rather than months. Or maybe even less: in 2013, a team of scientists at Novartis generated an mRNA vaccine candidate in the span of eight days.

Messenger RNA technology skips a large chunk of the usual vaccine manufacturing process by recruiting our very own cells as factories to make the antigen onsite, instead of having to produce it externally and administer it after the fact. All thats needed for the mRNA vaccines is the relevant sliver of genetic material and a protective lipid shell. The rest of the work is done by us, inside our cells.

The protective lipid shell is crucial. Messenger RNA on its own is very fragile and any free floating or misplaced mRNA molecules in our body are quickly chopped up and broken down by enzymes. Added to this is the fact that mRNA cannot enter cells on its own, meaning it would never even be able to deliver the necessary genetic instructions. Lipid nanoparticles (LNPs) form a bubble around the delicate mRNA, helping to shield it and shuttle it into our cells (Figure 1).

A big part of the reason mRNA technology wasnt introduced into the mainstream until recently is because finding the right combination of lipid nanoparticles had given researchers difficulties. In 2004, while working on small-interfering RNA (siRNA), which can selectively silence genes in mammalian cells, researchers at Alnylam Pharmaceuticals made a breakthrough: attaching a cholesterol molecule to the siRNA allowed it to pass through cell membranes. A later breakthrough improved on this discovery by adding a transient positive charge to the lipid nanoparticle, creating a bubble around the siRNA that protected it and helped ferry it into cells more effectively. Although designed for siRNA, the same delivery technology opened the door for improved mRNA therapeutics. In fact, Pfizer and Moderna used very similar lipid nanoparticles to ferry the mRNA in their respective Covid-19 vaccines. And according to Alnylam, the lipid nanoparticle formulation is too similar to its own, leading them to file a lawsuit against the two pharmaceutical companies.

FIGURE 1. A schematic diagram of lipid nanoparticles used to protect and shuttle mRNA (red) during ... [+] vaccination.

Messenger RNA vaccines may soon become even quicker and cheaper to produce by implementing self-amplifying mRNA (samRNA) technology. With conventional mRNA vaccines, the amount of mRNA in the vaccine is the amount of mRNA that will end up in the cell, and by extension, the amount of antigen produced. Self-amplifying technology combines the mRNA with enzymes from alphaviruses, which help the mRNA make copies of itself once inside the cell (Figure 2). This means fewer mRNA molecules need to be used per vaccine. The samRNA vaccines may also induce a more robust immune response, as the mRNA stays in the body for a longer period of time.

FIGURE 2. samRNA delivery system (left) compared to conventional mRNA delivery system (right).

Faster production should allow manufacturers to keep up with new viral mutations; as soon as a variant of concern pops up, researchers could begin production of a bespoke vaccine to neutralize it. In the case of influenza, mRNA technology would improve the odds of vaccines being well matched to the circulating wild type viruses something we continue to have trouble with, even as recently as this past flu season.

Drawbacks?

Unlike Covid-19 outbreaks, which are usually driven by one dominant circulating variant, seasonal flu outbreaks are characterized by multiple cocirculating strains. These strains are derived from the four main influenza viruses: influenza A(H3N2), influenza A(H1N1), and two influenza B viruses. To account for differences in the hemagglutinin surface protein between strains, traditional flu shots are quadrivalent, meaning they contain an inactivated version of each of the four viruses. But a synthesized mRNA sequence can only make one particular protein; an effective mRNA influenza vaccine would need four different sequences to make four different HA proteins. A 2020 study led by researchers at the Icahn School of Medicine at Mount Sinai suggests this shouldnt be an issue. The team of scientists manufactured an mRNA vaccine against an influenza subtype that encoded four different proteins at once. They have since repeated the experiment for two additional influenza subtypes, and they plan to test a combined vaccine that encodes for a total of 10 to 12 different antigens across subtypes. This is part of a larger movement towards mRNA flu shots.

A more serious concern is that mRNA technology comes at the cost of thermostability. The delicate nature of mRNA renders it thoroughly unstable at room temperature, leading to degradation and loss of quality. In general, mRNA vaccines need to be stored and transported well below freezing Pfizers Covid-19 vaccine needs to be stored at -94 Fahrenheit, colder than Antarctic winter. This makes global distribution and storage a serious challenge, especially in areas without ready access to electricity.

But, this too, is already becoming a problem of the past. A process known as lyophilization, or freeze-drying, allows researchers to dehydrate the mRNA solution and turn it into a powder. This powder is stable at room temperature and can be mixed with diluents just before administration. In 2017, researchers used this method to produce a rabies mRNA vaccine that retained its efficacy after being stored at 113 degrees Fahrenheit for 12 months. Even when stored at 158 degrees Fahrenheit for three months, the vaccine managed to protect mice from disease. In India, Gennova Biopharmaceuticals has just received emergency use authorization for their lyophilized Covid-19 mRNA vaccine, which can be stored between 35 to 45 degrees Fahrenheit without degradation. Instead of sub zero temperatures, standard refrigeration will do just fine.

What remains unclear is whether mRNA technology by itself could address a major issue plaguing current influenza vaccines: waning immunity. A 2018 meta-analysis of influenza vaccine durability found that protection can vanish as early as 90 days post vaccination. Recombinant and inactivated vaccines both suffer from this issue, even though they trigger immune responses in different ways. If the Covid-19 mRNA vaccines are anything to go by, waning immunity will likely continue to be a factor even if influenza vaccines made the switch to mRNA technology.

The next article in this series will look at the nasal spray flu vaccine live attenuated influenza vaccine [LAIV] which has faced a bumpy road ever since it was first introduced. What did it promise, and why has it fallen short?

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Getting a Grip on Influenza: The Pursuit of a Universal Vaccine (Part 3) - Forbes

What is the tomato flu? Scientists monitoring outbreak in India – FOX 35 Orlando

August 30, 2022

A view of the city skyline seen from the Police Headquarters at ITO during the first day of national lockdown imposed by PM Narendra Modi to curb the spread of coronavirus on March 25, 2020 in New Delhi, India. (Photo by Sonu Mehta/Hindustan Times vi

NEW DELHI, India - Researchers in India say they are monitoring an outbreak of the tomato flu, or tomato fever, in the country calling it a new virus as the world continues to grapple with the COVID-19 pandemic.

Their findings were recently published in the medical journal "The Lancet," saying cases have been detected in the state of Kerala in children younger than 5 years old.

They said so far, the rare viral infection is considered non-life threatening but they want to prevent further outbreaks.

According to the journal, the tomato flu virus has symptoms similar to COVID-19 such as fever, fatigue, and body aches. Symptoms can also include large, red blisters that can become the size of a tomatohence the name.

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Researchers believe the virus is "self-limiting" with no specific drug existing to treat it.

Meanwhile, they believe the virus is spread through close contact and urge people to practice proper hygiene and sanitization. They suggest people who have the virus to isolate five to seven days after the onset of symptoms.

Health experts advise getting tested by a health care provider but here are some key differences between COVID-19, the flu and the common cold as told by a nurse educator.

But whether or not the virus is "new" is up for debate among scientists.

The Lancet reported that the tomato flu was first identified in the Kollam district of Kerala in May 2022. As of July, more than 80 children, younger than 5, were diagnosed with the illness.

However, doctors in Europe said the tomato flu is not new and is a variant of the hand, foot, and mouth disease (HFMD), publishing their findings in The BMJ.

RELATED: US governments COVID-19 website to suspend free at-home tests

Currently, neither the Centers for Disease Control and Prevention nor the World Health Organization specifically points out tomato flu.

Researchers in India said more follow-ups and studies are needed to understand and treat the tomato flu.

This story was reported from Los Angeles.

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What is the tomato flu? Scientists monitoring outbreak in India - FOX 35 Orlando

Heres why you caught that summer cold, again – ThePrint

August 30, 2022

Colds and the flu are generally associated with colder weather, but there have been increased reports of people suffering from summer colds this year.

A number of factors could be responsible including pandemic-era lockdowns, mask wearing and social distancing giving us less exposure to common colds in recent years.

Heatwaves and humidity fluctuations in many countries may also have played a role in the transmission of common cold viruses this year.

The advice for getting over a summer cold is the same as it would be if you caught one in the winter drink plenty of fluids, get lots of rest and eat nutritious foods.

Most of us associate colds and the flu with colder weather. But that doesnt mean you cant still catch a cold during the summer. Some viruses are even more common in summer than in the winter.

Both viruses cause typical cold symptoms, including a runny nose, low energy, muscle aches, cough, headaches and sore throat. Parainfluenza can sometimes causebronchitis and pneumoniain people who have a poorly functioning immune system. While these symptoms are similar to allergies, the telltale difference is thatallergies tend not to causefevers or body aches, and rarely cause coughs. Colds last from a few days to two weeks, but, depending on what triggered the allergy, allergy symptoms can last all summer for some people.

It seems counter-intuitive that certain viral infections are more common in warmer months when we spend more time outdoors. But in the warmer months, we also socialise and travel more meaning were mixing with a greater number of people, sometimes from different parts of the world. Many of us also gravitate towards air-conditioned indoor environments when the weather is hot.

But the structure of a virus may also explain why some spread more easily in the warmer months.

For a virus to spread and infect healthy cells, it needs to survive both outside and inside the body and it also needs to use the machinery of human cells (such as their DNA) to create copies of itself.

Viruses are surrounded by a protein coat, called a capsid, which not only gives the virus its shape but also protects the genetic material inside. The capsid also helps the virus attach to human cells to cause infections.

Some viruses (called enveloped viruses) are also surrounded by a lipid (fatty acid) envelope. This viral envelope helps the virus to avoid being destroyed by the immune system. It also plays a role in interacting with human cells to cause infection.

Many winter viruses (including influenza and RSV) are enveloped viruses. Enveloped viruses tend to bemore vulnerable to heat and drynessthan viruses that lack envelopes. This is one of the reasons why its thought that these winter cold viruses survive best in colder winter environments.

While some summer colds (such as enteroviruses) lack an envelope, others (parainfluenza virus 3) have an envelope. In fact, parainfluenza virus 3 is more common whentemperatures are high and humidity is low(though it can survive in a range of different humidities). This suggests that other parts of a viruss structure, aside from the envelope, may play some role in what conditions it can best survive and spread in but more research will be needed to better understand this.

The interplay between temperature and the immune response to a virus may also play a role. One study found that mice exposed totemperatures of 36Chave a diminished immune response against the flu virus. However, more research is needed to confirm this finding in humans.

Immune response

Many people have reported suffering from summer colds this year, leaving many to wonder why this is the case and if the pandemic has played a role.

Immunity to common cold viruses is short-lived. So each season, when we are exposed to new variants, our immune system has to adapt. But during the pandemic, various lockdown measures, such as distancing and wearing masks, limited the exposure that many people had to these viruses.

When we gathered again after lockdown,cold viruses began to circulate, but our immunity had not been boosted by exposure to that virus the previous year. While the predictability of seasonal viruses has changed since the emergence of COVID, the increases in summer colds seen this year are probably due to us travelling more, more social mixing, less mask wearing and distancing, and less exposure to respiratory viruses the previous year.

This year many parts of the world have also seen extremely hot temperatures and a spate of heatwaves. These temperatures and humidity fluctuations may have played a role in the transmission of common cold viruses this year. These factors will also become even more relevant in the future and may even change what time of year we see certain viruses. Climate change may furtherworsen the spreadofviruses in the future.

Since theres no vaccine for summer colds, the best thing you can do to avoid getting one is to stay away from people who are sick (if possible), wash your hands and avoid touching your face. If youre unlucky enough to have gotten one, the advice for getting over a cold is the same as it would be if you caught one in the winter: drink plenty of fluids, get lots of rest and eat nutritious foods. To protect others, coughing or sneezing into your elbow or tissues is also recommended.

It may also be worthwhile thinking about how you can protect yourself from getting sick as the temperatures cool in the coming months. The flu vaccine is recommended each winter for certain people, so its wise to check if you are due for a flu vaccine this year. This year the flu has been particularly bad for Australia, and predictions suggest it willbe the samefor many parts of the world this winter.

Thearticle originally appeared in the World Economic Forum.

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Heres why you caught that summer cold, again - ThePrint

What is tomato flu? Very contagious virus detected in kids, docs warn – New York Post

August 20, 2022

As the world continues its fight against COVID-19 and the ever-spreading monkeypox virus, it seems as though theres another illness gaining a foothold.

Tomato flu was first identified in India on May 6 and has so far infected 82 children, who are all under the age of 5, according to a study by the Lancet Respiratory Medicine Journal.

A further 26 kids up to the age of 10 are suspected of having cases of tomato flu.

Aptly named for the red blisters that appear on the skin, the new virus comes armed with fever and joint pain.

Just as we are dealing with the probable emergence of fourth wave of COVID-19, a new virus known as tomato flu, or tomato fever, has emerged in India in the state of Kerala in children younger than 5 years, the Lancet reported.

The rare viral infection is in an endemic state and is considered non-life-threatening; however, because of the dreadful experience of the COVID-19 pandemic, vigilant management is desirable to prevent further outbreaks.

The virus has so far been detected in the Kollam district of Kerala, India, and nearby areas of Anchal, Aryankavu and Neduvathur.

Children are at increased risk of exposure to tomato flu as viral infections are common in this age group and spread is likely to be through close contact, Lancets report added.

Medics say the infection, which currently has no drug to fight it, is very contagious and has striking similarities to hand, foot and mouth disease.

Given the similarities to hand, foot and mouth disease, if the outbreak of tomato flu in children is not controlled and prevented, transmission might lead to serious consequences by spreading in adults as well, the study added.

Other reported symptoms include vomiting, diarrhea, dehydration and body aches.

Some cases, albeit very few, reported a change in limb color.

It is not a fatal disease, but it is contagious and can spread from person to person, although the actual ways in which the infection spreads are still being studied, Dr. Subhash Chandra, assistant professor of Internal Medicine at Amrita Hospital told India Today.

Patients who develop tomato fever should drink plenty of fluids and rest in bed, as it is also advised for other viral fevers, to keep the body hydrated and well-rested.

Those who contract the virus are placed in isolation for 5 to 7 days.

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What is tomato flu? Very contagious virus detected in kids, docs warn - New York Post

Flu Viral: Here Are The Most Common Queries Answered – NDTV

August 20, 2022

Flu and viral: If you are down with the flu, you must isolate yourself to limit spread

A viral infection is known as influenza. It targets the respiratory system, including the nose, throat, and lungs. Although influenza is frequently referred to as the flu, it differs from stomach "flu" viruses that cause vomiting and diarrhoea. The flu often goes away on its own for most people. But occasionally, influenza and its side effects might be fatal.

Understanding the flu, its symptoms, prevention, and treatment can help you better deal with it. In this article, we discuss some of the most frequently asked questions regarding the flu.

1. How are flu virals spread?

Flu virals can spread in various ways. They may spread through airborne respiratory droplets (coughs or sneezes), touching a contaminated surface, saliva (kissing or shared drinks), skin-to-skin contact (handshakes or hugs), etc.

2. What causes flu spike in monsoon?

The sudden change in weather and fluctuation in temperature can cause influenza. Low immunity is also a reason. The best time for pathogenic microorganisms to reproduce is regarded to be the monsoon season, also referred to as the flu season.

The monsoon season has greater rates of disease than other times of the year because of the humidity, dirt, and standing water that function as a breeding ground for many viruses and bacteria. At this time of year, adopting a healthy lifestyle and improving living conditions can be effective preventative measures.

3. How can we prevent getting virals?

Physician Dr. Balamurugan suggests, The best way to prevent the flu is through annual vaccinations. Each flu shot protects against three to four different influenza viruses within that year's flu season.

Other ways to prevent spreading this disease include washing hands regularly, avoiding large crowds specifically during a flu outbreak, covering mouth and nose when cough or sneeze, staying home. Adds Dr. Balamurugan.

4. Should viral patients isolate? If yes, for how long?

Yes, 4 to 5 days after the onset of symptoms. The virus is transmissible and can transfer from one sick person to the other. Make sure to isolate and stay at home to reduce the spread.

5. Do flu virals cause long-term damage to us?

The flu can have some long-term effects, like increased risk of heart attack and stroke. And can worsen long-term medical conditions, like congestive heart failure, asthma, or diabetes. Mentions Dr. Balamurugan. Hence, it is ideal to seek the necessary vaccine and medication. Prevention is better than cure. You are encouraged to follow necessary preventive measures.

6. How to treat flu virals?

Dr. Balamurugan suggests, Flu is primarily treated with rest and fluid intake to allow the body to fight the infection on its own. Decongestant, Cough medicine, Nonsteroidal anti-inflammatory drug, Analgesic, and Antiviral drug. An annual vaccine can help prevent the flu and limit its complications.

7. How helpful is the influenza vaccine?

Flu vaccination can reduce the risk of flu-associated hospitalization. Flu vaccination has been shown in several studies to reduce the severity of illness in people who get vaccinated but still get sick. It is an important preventive tool for people with certain chronic health conditions. Vaccination helps protect pregnant people during and after pregnancy and may even be lifesaving in children.

In conclusion, proper care and isolation can help lower the spike in flu cases this monsoon. Proper vaccines and medication help eradicate the flu without causing severe damage to our bodies.

Disclaimer: This content including advice provides generic information only. It is in no way a substitute for a qualified medical opinion. Always consult a specialist or your own doctor for more information. NDTV does not claim responsibility for this information.

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Flu Viral: Here Are The Most Common Queries Answered - NDTV

Getting a Grip on Influenza: The Pursuit of a Universal Vaccine (Part 2) – Forbes

August 20, 2022

Taiwan researchers sort through eggs used for the cultivation of swine flu vaccine, in a plant in ... [+] Taichung, on June 18, 2009. Taiwan is set to mass produce swine flu vaccine in October, as the island's confirmed cases rose to 58 as of June 17. AFP PHOTO/PATRICK LIN (Photo credit should read PATRICK LIN/AFP via Getty Images)

This is a short series about a recent breakthrough on the road to developing a much sought-after broadly neutralizing vaccine against all influenza A viruses. If successful, it may act as a precursor to a truly universal flu vaccine, one that protects against all types, subtypes, and lineages of the virus. The breakthrough may also provide a blueprint for developing a Covid-19 vaccine that retains its efficacy in the face of new variants.

In the first part of this series, I gave a brief overview of the history and nature of influenza viruses, including why it has been so difficult to develop successful vaccines. The next few articles discuss some of the attempts that have been made to overcome these challenges, including their shortcomings. And in the last installments, I will offer a detailed analysis of the latest and most promising advances in the field.

The Seasonal Approach

Picking up where we left off in the previous article, any successful influenza vaccine has to account for the ability of influenza viruses to mutate. Genetic mutations to vital proteins can lead to antigenic variation changes to parts of the virus that our immune system relies on to stimulate its memory. Although various different parts of the virus serve as antigens, the surface proteins that help it enter and exit host cells are some of the most important. Changes to these proteins can prevent our antibodies from recognizing the virus, rendering them unable to block its spread. Antigenic variation is responsible for influenza reinfections, leading to seasonal flu outbreaks.

In an attempt to circumvent the issue of antigenic variation, vaccine manufacturers update the flu shot each year based on the latest circulating influenza strains. The idea is to expose our immune system to the antigens it is most likely to encounter during flu season, helping it to build up its antigen-specific defenses in advance once our immune system has built up its memory, it can jump into action straight away should we become infected.

Which influenza strains ultimately get used to make the yearly flu shot is decided on the basis of data collected throughout the year by the World Health Organizations (WHO) Global Influenza Surveillance and Response System (GISRS). This surveillance and response system is made up of roughly 150 different laboratories spread across the globe, each of which gathers thousands of influenza samples from sick patients. The most prevalent viral strains are then shared with five WHO Collaborating Centers for Influenza, which perform further analysis. Two times a year once in preparation for flu season in the Northern Hemisphere, and another in preparation for flu season in the Southern Hemisphere Directors of the WHO Collaborating Centers, Essential Regulatory Laboratories, and representatives of a few of the smaller national laboratories come together to: review the results of surveillance, laboratory, and clinical studies, and the availability of flu vaccine viruses and make recommendations on the composition of flu vaccines. Once the WHO vaccine composition committee has made its recommendations, each country makes a final decision on which viruses they will choose to use in their flu vaccines.

In the United States, all influenza vaccines are quadrivalent, meaning they contain four different influenza viruses. This is done to broaden protection against the various influenza subtypes and lineages known to drive seasonal outbreaks: influenza A (H1N1), influenza A (H3N2), influenza B/Victoria, and influenza B/Yamagata. Quadrivalent vaccines will also protect against any other influenza viruses that are antigenically similar.

Although this may seem like a relatively reliable process, there is one glaring drawback to the seasonal vaccination approach: vaccines produced in this way are nowhere near as effective as we might hope. At best, they protect 60% of people from illness, but this number can, and often does, drop much lower. For the influenza A (H3N2) subtype, vaccine effectiveness hovers around 33%. Of course, any protection is better than no protection, but it is still suboptimal remember, these numbers represent best case scenarios, years where the viruses selected for use in vaccines are well matched to those that actually end up circulating during the flu season. So, where are things going wrong?

Missing the Target: Egg-based Vaccines

Selection of candidate vaccine viruses (CVVs) is only one part of the equation, growing them is another. This is no simple feat considering they need to be available in bulk, enough to make millions of vaccines. For the past 70 years, the majority of manufacturers have turned to chicken eggs in order to achieve the necessary growth (Figure 1). The candidate vaccine viruses are injected into fertilized hens eggs and left to incubate for a few days. During this period, the viruses are able to replicate. The fluid in the eggs is then extracted and the viruses are killed (inactivated). Finally, the antigen of choice usually the hemagglutinin surface protein is isolated from the killed viruses and purified, making it ready for use in vaccines. Even now, most flu vaccines continue to be egg-based.

FIGURE 1. An overview of the steps involved in producing egg-based vaccines.

But there are two issues with this approach. First, growing the viruses in eggs is a fairly slow process. This means the selection of candidate vaccine viruses has to happen far in advance of flu season, to make sure manufacturers have enough time to produce the amounts needed. In the six to nine months it takes to grow and purify enough virus, the wild type influenza strains continue to mutate and change. If these changes impact the antigen, the wild type viruses may escape the immunity that the vaccines provide us, reducing their effectiveness. When this happens, the viruses are referred to as escape mutants.

A growing body of research suggests that a second factor may be even more important: egg-adapted changes. Because the candidate vaccine viruses are human influenza viruses, growing them in chicken eggs carries the risk that they adapt to the new immune niche while replicating. The immune niche of chickens is different to that of humans, so adaptations that improve viral fitness in chickens may result in genetic and antigenic changes to the viruses. As before, these changes can lead to a drop in vaccine effectiveness, since the vaccine strains no longer resemble the circulating wild type strains; the egg-adapted vaccines end up training our immune system to recognize the wrong viruses, thus hampering its ability to respond efficiently come flu season.

Egg Substitutes: New Ways of Growing Candidate Viruses

In response to these issues, manufacturers have tried to develop new production methods that avoid using chicken eggs to culture candidate viruses. This search has led to a cell-based approach and a recombinant approach (Figure 2).

FIGURE 2. Timeline of current influenza vaccine production methods. Schematic overview of egg-based, ... [+] cell-based and protein-based (recombinant) influenza vaccine production.

Cell-based vaccines are produced using candidate viruses grown in mammalian cells rather than chicken eggs. Aside from this, the manufacturing process between the two is virtually identical: candidate vaccine viruses are grown in mammalian cell cultures by the CDC, these are then handed over to private manufacturers who inoculate the viruses into mammalian cells, the viruses are left to replicate for a few days before being harvested, and finally, purified. Although approved in 2012, it wasnt until this past 2021-2022 flu season that fully egg-free, cell-based vaccines were produced previously, the initial production of candidate vaccine viruses by the CDC was still done using fertilized hens eggs, and only after being handed over to the private sector were the viruses mass-produced in mammalian cells.

Using the cell-based approach eliminates egg-adapted changes in candidate viruses, keeping the viruses as close as possible to the wild type influenza strains predicted to circulate during flu season. An added benefit of cell-based vaccines is that the production process can be scaled up more quickly; mammalian cells can be frozen in advance to ensure steady supply, which could prove especially useful during pandemic outbreaks.

In theory, the lack of egg-adapted changes should improve vaccine effectiveness. But what about in practice? Although there still hasnt been enough research for a clear consensus to develop, initial findings suggest the difference in effectiveness is modest at best, and statistically insignificant at worst. This hints that egg-adapted changes might not play as important of a role as initially suspected; low vaccine efficacy can occur even when eggs are not used in the manufacturing process. That said, the 2021-2022 flu season marks the first time truly egg-free cell-based vaccines in which all four viruses are derived entirely through cell-based methods were used, so perhaps future research will yield different results. For now, things dont look too promising.

Recombinant vaccines provide a third option, and manage to overcome a crucial issue faced by the other two options: the lengthy, tedious virus production process. Whereas egg- and cell-based vaccines depend on candidate virus samples, recombinant manufacturing skips this step. Instead, recombinant vaccines are made by isolating the gene that makes the hemagglutinin surface protein from a wild type influenza virus. Once isolated, this gene is combined with a different kind of virus, called baculovirus. The new virus is known as a recombinant baculovirus and it is used to ferry the gene that makes the hemagglutinin antigen into a host cell line. As soon as the gene enters the cells, they begin to mass produce the hemagglutinin antigen. The antigen can then be extracted and purified before being assembled into a vaccine.

Given that they are entirely egg-free and dont require candidate virus samples, recombinant vaccines bypass the issue of egg-dependent changes. Due to the speed of production, there is also a decreased risk of escape mutants developing. As before, there is a paucity of comparative research, making it difficult to draw any firm conclusions, but early findings suggest recombinant vaccines may be more effective than traditional egg-based and cell-based vaccines, including improved antibody production.

Takeaway

Developing consistently protective influenza vaccines has proven difficult, with effectiveness frequently hovering somewhere between 40 and 60%. Too low, considering the threat posed by influenza.

A big part of the challenge is the mutability of the virus; it is constantly changing, making it hard for our immune system to keep up and retain useful memories of previous encounters. In response, public health agencies and scientists around the world develop new vaccines every year that prime our immune systems for the latest circulating strains. Sometimes scientists miss the mark with their predictions, in which case the circulating influenza strains do not match up with those in the vaccine, undermining vaccine effectiveness. At other times predictions are right on the money, but the vaccine production process impairs effectiveness either by being too slow and giving the wild type viruses time to mutate again, or because of mutations to the candidate vaccine strains during mass-production in chicken eggs.

Cell-based and recombinant vaccines aim to resolve the issues on the production side of things. The former by skipping the need for eggs, and by extension, the threat of egg-adapted changes. The latter by skipping the need for eggs as well as cutting down the time it takes to produce the vaccines, reducing the risk of escape mutants. Despite these advances, vaccine effectiveness has not yet seen the boost it needs.

The below table gives a summary of the advantages and disadvantages associated with these three production processes.

FIGURE 3. Advantages and disadvantages of strategies for influenza virus vaccine production.

The next article in this series will look at two additional technologies: intranasal vaccines and mRNA vaccines. Might they succeed where the more traditional strategies have wavered?

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Getting a Grip on Influenza: The Pursuit of a Universal Vaccine (Part 2) - Forbes

Summer colds: this may explain why so many have suffered them this year – The Conversation

August 20, 2022

Most of us associate colds and the flu with colder weather. But that doesnt mean you cant still catch a cold during the summer. Some viruses are even more common in summer than in the winter.

The flu virus and respiratory syncytial virus (RSV) are more common in the winter months, as the colder temperatures and more time spent indoors around other people provide them with favourable conditions to spread.

But in the summer, enteroviruses and parainfluenza 3 virus are much more common, with infections from these viruses tending to peak in summer and early autumn when the weather is warmer and more humid.

Both viruses cause typical cold symptoms, including a runny nose, low energy, muscle aches, cough, headaches and sore throat. Parainfluenza can sometimes cause bronchitis and pneumonia in people who have a poorly functioning immune system. While these symptoms are similar to allergies, the telltale difference is that allergies tend not to cause fevers or body aches, and rarely cause coughs. Colds last from a few days to two weeks, but, depending on what triggered the allergy, allergy symptoms can last all summer for some people.

It seems counter-intuitive that certain viral infections are more common in warmer months when we spend more time outdoors. But in the warmer months, we also socialise and travel more meaning were mixing with a greater number of people, sometimes from different parts of the world. Many of us also gravitate towards air-conditioned indoor environments when the weather is hot.

But the structure of a virus may also explain why some spread more easily in the warmer months.

For a virus to spread and infect healthy cells, it needs to survive both outside and inside the body and it also needs to use the machinery of human cells (such as their DNA) to create copies of itself.

Viruses are surrounded by a protein coat, called a capsid, which not only gives the virus its shape but also protects the genetic material inside. The capsid also helps the virus attach to human cells to cause infections.

Some viruses (called enveloped viruses) are also surrounded by a lipid (fatty acid) envelope. This viral envelope helps the virus to avoid being destroyed by the immune system. It also plays a role in interacting with human cells to cause infection.

Many winter viruses (including influenza and RSV) are enveloped viruses. Enveloped viruses tend to be more vulnerable to heat and dryness than viruses that lack envelopes. This is one of the reasons why its thought that these winter cold viruses survive best in colder winter environments.

While some summer colds (such as enteroviruses) lack an envelope, others (parainfluenza virus 3) have an envelope. In fact, parainfluenza virus 3 is more common when temperatures are high and humidity is low (though it can survive in a range of different humidities). This suggests that other parts of a viruss structure, aside from the envelope, may play some role in what conditions it can best survive and spread in but more research will be needed to better understand this.

The interplay between temperature and the immune response to a virus may also play a role. One study found that mice exposed to temperatures of 36C have a diminished immune response against the flu virus. However, more research is needed to confirm this finding in humans.

Many people have reported suffering from summer colds this year, leaving many to wonder why this is the case and if the pandemic has played a role.

Immunity to common cold viruses is short-lived. So each season, when we are exposed to new variants, our immune system has to adapt. But during the pandemic, various lockdown measures, such as distancing and wearing masks, limited the exposure that many people had to these viruses.

When we gathered again after lockdown, cold viruses began to circulate, but our immunity had not been boosted by exposure to that virus the previous year. While the predictability of seasonal viruses has changed since the emergence of COVID, the increases in summer colds seen this year are probably due to us travelling more, more social mixing, less mask wearing and distancing, and less exposure to respiratory viruses the previous year.

This year many parts of the world have also seen extremely hot temperatures and a spate of heatwaves. These temperatures and humidity fluctuations may have played a role in the transmission of common cold viruses this year. These factors will also become even more relevant in the future and may even change what time of year we see certain viruses. Climate change may further worsen the spread of viruses in the future.

Since theres no vaccine for summer colds, the best thing you can do to avoid getting one is to stay away from people who are sick (if possible), wash your hands and avoid touching your face. If youre unlucky enough to have gotten one, the advice for getting over a cold is the same as it would be if you caught one in the winter: drink plenty of fluids, get lots of rest and eat nutritious foods. To protect others, coughing or sneezing into your elbow or tissues is also recommended.

It may also be worthwhile thinking about how you can protect yourself from getting sick as the temperatures cool in the coming months. The flu vaccine is recommended each winter for certain people, so its wise to check if you are due for a flu vaccine this year. This year the flu has been particularly bad for Australia, and predictions suggest it will be the same for many parts of the world this winter.

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Summer colds: this may explain why so many have suffered them this year - The Conversation

Monkeypox transmission, vaccines and treatment | HealthFocus SA | University Health – University Health System

August 20, 2022

Dr. Jason Bowling clears up common questions about the monkeypox outbreak, including information on vaccines, transmission and treatment of the virus.

Monkeypox is an orthopox virus. It is in the same family of viruses that includes smallpox, which people are very familiar with, and vaccinia virus. Vaccinia virus is important because its used in the vaccine that helps prevent smallpox and monkeypox.

The symptoms of monkeypox are similar to the symptoms of smallpox, but theyre much milder. In a typical syndrome with monkeypox, people will start off with fever, muscle aches, fatigue general non-specific viral infection symptoms.

After about a day or two of those symptoms, they can start to develop a rash, which classically began on the face, the arms and the legs, and maybe moves to the trunk.

What were seeing with the outbreak that started this year is that the symptoms can be a little bit different. Sometimes people dont have the initial fever and muscle ache they may just start off with a rash. And the rash may not be as distributed throughout the body. They may only have a few lesions.

Many of the people in this current outbreak have lesions in the genital area or perigenital area, so its a little bit different than the classic presentation were familiar with from prior outbreaks and infections with monkeypox.

If you know that youve been exposed to somebody that has confirmed monkeypox, its important to reach out to your medical provider. Public health might be reaching out to you because theyre doing contact tracing on people that have known exposures so they can provide them with vaccine to hopefully reduce their risk of having monkeypox.

Otherwise, if you dont have a known exposure but if you have a fever and a rash, thats something youd want to get evaluated. Again, this rash can look different for different people.

It tends to start as flat lesions and then it can progress to what looks like little bumps or pimples, and then move into blisters before it starts to scab over and eventually fall off with new skin, kind of like what you see with someone with chickenpox. The rash can be really painful initially, and then as it starts to scab and fall off, it can be really itchy.

Testing for monkeypox right now is through a PCR test, but its PCR testing of skin lesions, so you have to have the skin lesion or rash to get tested. Your provider will swab the top of the rash a couple of times, and those swabs will be sent off to the specialized lab where they do PCR testing to confirm that its monkeypox.

Monkeypox can be caused by a couple of different strains. Fortunately the strain thats causing this current global outbreak and the cases in the United States is causing milder infections. So fortunately, most people who get monkeypox have symptoms that go away and they dont end up in the hospital.

In the United States outbreak there havent been any deaths so far. Its not as serious as it could be, and fortunately most people dont end up in the hospital, but its still something to be aware of.

Monkeypox can leave scars. Any time you have a viral infection that causes a rash, theres a potential that you could get an infection of the rash, you could get scars from that, similar to having chickenpox or other viruses that cause a rash.

But most people dont. The lesions will resolve, theyll scab over and the new skin will form.

And it doesnt seem to cause long-lasting symptoms like we hear about with long-COVID. Well need to continue to follow this monkeypox outbreak, this is a little bit different than monkeypox outbreaks weve seen in the past, but so far were not seeing long-lasting symptoms other than the disease itself which lasts about two to four weeks. But after its resolved, people are not complaining of long-lasting symptoms.

There is treatment for monkeypox. Fortunately most people in this outbreak have not required treatment, theyve just have supportive care, which means they stay hydrated, they rest at home and they take some ibuprofen or Tylenol as needed for pain or fever. But they havent required specific treatment.

There is a treatment available through the CDC. This treatment is actually approved for smallpox, and its in the national stockpiles in case we had an outbreak of smallpox, which fortunately we do not have. But it can also be used to treat monkeypox, and its reserved for people who have severe cases of monkeypox.

So if it was a rare case that ended up in a hospital or an immunocompromised person, or somebody who had skin lesions in a place that was causing problems like in the throat and you were unable to eat or drink, that might be a good candidate for treatment.

Their provider would apply through the CDC to get this medication to treat it. The treatment comes in pill form that you can take by mouth, or through an IV, so you can get it in a couple of different ways.

There is still some ongoing study with this outbreak so we can have a better understanding of that. The predominant way its being spread is by prolonged skin to skin contact with someone that has lesions of monkeypox. This can happen with close encounters, intimate encounters, sexual encounters, but its actually the skin to skin itself, not what we normally think of with sexually transmitted diseases where its being transmitted by other bodily fluids.

Theres still ongoing research to see what other bodily fluids contain monkeypox. It can also be transmitted if there is contaminated bed sheets or clothing from somebody that has the monkeypox lesions. Those pustules can have fluid in them and if that fluid contaminates sheets and someone handles those sheets, thats another potential avenue of getting infected.

It can also be transmitted by large respiratory droplets, but its not clear how effective its transmitted in that way. They havent had, so far in this outbreak with these contact tracings, found anyone thats contracting monkeypox from a casual conversation with somebody else. And even with somebody thats traveled in an airplane close to somebody else with monkeypox, they havent seen transmission that way or through health care encounters.

So respiratory doesnt seem to be as effective a means of transmission. Itd be something youd be concerned about for household contact someone that spends a prolonged time talking to somebody closely could potentially be a method of transmission.

Monkeypox is an envelope virus, which means it responds readily to disinfectants. Its like SARS-CoV-2, the virus that causes COVID-19, or influenza virus, which causes the flu. All of those respond really well to EPA-registered disinfectants.

If youre going to disinfect surfaces in your house to check the label. Theres an EPA-registered number on there and you can see if its registered for that. If its active against flu its going to be active against monkeypox.

Hand hygiene is important, so washing your hands with soap and water or an alcohol-based hand rub.

For silverware and plates, its important that you can use the dishwasher so you dont have to use separate utensils if someone else in the house had monkeypox and you were trying to not get it yourself, its okay if you run it through the dishwasher with hot water and detergent or if you hand wash it with hot water and soap.

The short answer is two to four weeks it depends on the skin lesions.

One of the challenges with monkeypox infection is that it lasts for a while. A person can potentially be transmissible from the skin lesions, which are the major way that someone should transmit it to somebody else, until those skin lesions have scabbed or fallen off or new skin has grown there. That can take around two to four weeks in an average case of monkeypox, so people are potentially transmissible in that time period.

The CDC would ideally like somebody to stay home that whole time period, but practically speaking that may not be feasible. Whats important is if someone leaves the house, if they have to go to the grocery store or something else, is that they keep all of those skin lesions covered. They can wear long sleeves, they can wear pants and gloves.

Its also recommended if theyre going to have prolonged face to face contact with somebody, the person with monkeypox should wear a well-fitting mask.

JYNNEOS is the vaccine thats currently available and recommended for preventing monkeypox. The challenge is theres not a huge supply of that right now. The vaccine manufacturer is working on making more JYNNEOS vaccine so that we can distribute it more widely in the United States and globally so we can cut down this outbreak faster.

The initial dosing of the JYNNEOS vaccine its a two-dose vaccine you give a dose and four weeks later you give a second dose. It was studied by giving it through the subcutaneous tissue, which is the layer of fat right underneath the skin like a standard vaccine.

However, theyve studied and seen that if you give the injection in the skin layer itself, not going through to the fat but stopping in the skin layer, you can still get a good immune response while using less vaccine. You can actually use one-fifth or 20% of the vaccine amount and still get a good response.

By doing that, we can extend the limited vaccine supply by five. So because of that, its recommended for people that are age 18 and older that are getting the monkeypox vaccine that it be administered in the skin layer itself so we can have more doses for everybody.

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Monkeypox transmission, vaccines and treatment | HealthFocus SA | University Health - University Health System

Why is swine flu surging in Maharashtra? What are the symptoms? – The Indian Express

August 20, 2022

In the first 12 days of August, Maharashtra reported nearly 900 new cases of swine flu with 23 fatalities linked to the infection. This is almost a 162 per cent increase over the total swine flu cases and toll, 552 and 20 respectively, which the state had reported since the beginning of the year till July 31.

With the massive uptick in cases this month, the state has so far reported a total of 1,449 cases and 43 deaths, with Pune, Kolhapur and Nashik recording the most number of fatalities.

What is swine flu or H1N1?

The influenza viruses belong to the Orthomyxoviridae family. Of the four genera described, the influenza A virus is the one that infects humans most commonly. The virus has proteins called hemagglutinin (H) and neuraminidase (N), both of which help it infect cells in the human respiratory and gastrointestinal tract. There are at least 18 H subtypes and 11 N subtypes, and combinations of these are used to denote the type of strain. Swine flu named as it was a reassortment of human, pig, and bird influenza viruses is a type of influenza A virus. It has the H1 and N1 subtypes of these proteins and is hence called H1N1. It was responsible for a pandemic in the year 2009, and since then, H1N1, H3N2 and some Influenza B strains have been the predominant strains circulating worldwide.

Why is the state witnessing such a surge in cases this year?

The virus is known to peak during the monsoon. The surge this year could be a combination of three factors first, this is the first monsoon since 2020 without lockdowns. Second, it is possible that COVID-19 has made people more aware and they are accessing healthcare earlier. Third, there is a widespread acceptance of getting nasopharyngeal swabs and better access to diagnostic test kits, leading to increased testing. However, it is possible that this is a genuine surge, and what we are witnessing is an exceptional year.

It has been witnessed that in alternative years, the state/Mumbai reports a large number of swine flu cases. What are the epidemiological reasons behind it?

Reassortment of viral proteins on the surface of the influenza virus can occur every few years. This can render existing immunity from past infections ineffective, as the virus evades the antibodies formed as a result of exposure to the earlier strains. Such antigenic drifts can cause year-to-year variability. Once every decade or so, larger changes in the virus (antigenic shift) can have the potential of causing a big spike. So, the creation of a new strain can have the same effects as the ancestral strain had on a native population.

How are the symptoms of COVID-19 different from swine flu? How can a person differentiate the symptoms?

Symptoms are similar and can be difficult to distinguish. Fever, nasal congestion, headache, sore throat, muscle aches and pains, cough are manifestations of both infections. Diarrhoea can also be seen in both. Secondary bacterial infections are possibly commoner in influenza than what we have witnessed in COVID-19 over the past two years. In the absence of having a documented close contact with someone who has influenza, it is impossible to distinguish between influenza and COVID-19, based on symptoms. Testing is the only way to confirm the infection.

What are the precautionary measures people should take?

Similar to COVID-19, influenza tends to cause the most severe disease among those with compromised immunity. These would include individuals who are elderly, those with immuno-suppressive conditions or on medication which suppress immunity, pregnant women, and those with comorbidities. Such individuals should especially avoid crowded spaces, closed, poorly ventilated areas and mask up especially when indoors. The annual influenza vaccine is protective, and those who have not received it this year should do so after consulting their doctor. Frequent hand-sanitising and isolating when sick are useful drills to protect oneself and close contacts. Oseltamivir, when started early, can potentially reduce the duration of illness and transmissibility, and would be recommended, especially for high-risk individuals.

What kind of patients are requiring hospitalisation?

Most individuals who have severe disease tend to be immuno-compromised. Influenza can often make individuals vulnerable to secondary bacterial infections after the initial viraemic phase and one needs antibiotics if there are indicators of a secondary infection. Viral respiratory infections are known to worsen underlying chronic diseases, and those with respiratory diseases such as COPD, asthma and underlying heart disease are especially vulnerable.

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Why is swine flu surging in Maharashtra? What are the symptoms? - The Indian Express

3 cases of avian flu now suspected in Nunavut – CBC.ca

August 20, 2022

Three birds in Nunavut are thought to have died from avian influenza recently.

On Friday, the territorial government announced a third suspected case of the flu. The first two were announced Aug. 5.

The most recent case was detected in a herring gull on Tukarak Island near Sanikiluaq, a community of about 1,000 people. That's south of Coats Island, where one of the other cases was detected in a live thick-billed murre. The flu has also been detected in a herring gull near Cambridge Bay.

All of the cases have been reported to the Nunavut government from the federal government's Canadian Wildlife Service.

Cases of avian influenza havenow been reported in all provinces and territories except for the N.W.T.

In a public health advisory Friday, Nunavut's Department of Health said the risk to humans is low, but people should take precautions when handling wild birds. Generally speaking, cases of transmission to humans happen through close, lengthy contact with infected birds or contaminated environments.

There is no evidence that the virus can be transmitted to people if they eat fully cooked birds or eggs.

People should wear gloves, wash their hands with soap and water, and clean dirty clothes and equipment as soon as possible if they harvest wild birds and eggs, the department stated.

Signs that birds may have avian flu include nervousness, trembling or lack of co-ordination, swelling around the head, neck and eyes, and diarrhea or sudden death.

If you come across more than one dead bird in an area, that's a sign the virus is present too.

If you feel sick after handling a bird, you should contact your local health centre. If you notice unusual death or illness in birds, you can contact the local conservation office for your community.

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3 cases of avian flu now suspected in Nunavut - CBC.ca

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