Virus World

Moderna said it will talk with regulators to figure out next steps for its combination COVID-flu vaccine and will present data at an upcoming medical conference.

Millions of Americans got both shots at the same time this winter following a major White House public health push, which said: God gave us two arms - one for the flu shot and the other for the Covid shot.' Getting Pfizer's Covid bivalent booster and a flu shot on the same day may raise the risk of a stroke, a small official analysis suggests. The Food and Drug Administration (FDA) found the preliminary link while scouring vaccine injury databases after a separate safety concern was raised about Pfizer's jab. FDA officials who have been investigating the link said most of the patients had also received their flu shot on the same day, which might be a factor. Millions of Americans got both shots at the same time this winter following a major public health push by the White House. In September, Dr Ashish Jha, White House Covid Response Coordinator, said: 'I believe this is why God gave us two arms — one for the flu shot and the other for the Covid shot.' The FDA is launching a bigger study to examine potential safety problems arising from vaccinating against Covid and flu simultaneously. The findings will help the agency decide whether to continue with its recommendation to get both vaccines at the same time next winter.

For now health officials are still recommending people get both shots at once because getting infected with flu or Covid also raises the risk of strokes.  Dr Walid Gellad, professor of medicine at the University of Pittsburgh who was not involved in the analysis, said the issue required further investigation. 'Sometimes signals are not clear. It makes sense to look into it more, and it doesn't make sense to change practice given the known benefits (of getting the booster) in this age group.' The possible link between the shots and strokes was found as part of an independent FDA review into Pfizer's Covid vaccine.  The findings were presented today at a meeting of outside experts that advise the FDA on vaccine policy. In November, a small real-time government surveillance system that monitors vaccine injuries known as the Vaccine Safety Datalink (VSD) detected a possible link between the Covid shot and strokes among over-65s. Investigators found that 130 seniors suffered strokes in the 21 days after receiving Pfizer's booster among about 550,000 recipients in the VSD database.  One man in his 70s died a month after the stroke, which was determined his likely cause of death. But officials said the overall increase in strokes seems to wane with time, weakening the link to the Covid shot. Richard Forshee, deputy director of the FDA's biostatistics office, told the agency's independent vaccine committee: 'So far the data that we have seen suggests the absence of a safety risk for the bivalent boosters in age 65 years and older.'

The FDA reviewed data from 4.25 million seniors who received Pfizer's omicron booster and did not identify any increased stroke risk.  The agency's review of VAERS database also did not find an increased risk. The FDA also reached out to international health agencies and Pfizer to find out what they observed in their data, and the stroke link was not corroborated. However, the FDA reviewers ran a small analysis that indicated seniors who received both the Pfizer omicron booster and a high-dose or adjuvanted flu vaccine on the same day may have a higher risk of stroke. Its comes as a key panel of advisors to the FDA recommended switching the entire vaccine series to bivalent booster doses. Currently, a person receiving the original two-dose vaccine regimen will receive the original vaccine doses tailored to the Wuhan strain, but the bivalent shot as a booster. The Vaccines and Related Biological Products Advisory Committee, which is made up of outside experts that advise regulators, voted 21-0 to make the original regimen the bivalent shots too. The FDA will now need to approve of this change, which it is likely to do in the coming days. While it will only impact people who are still unvaccinated against the virus, the change could be a key step towards making the Covid vaccine an annual shot - like it is for the flu.

An international team of researchers has used mRNA technology to develop an influenza vaccine that targets four proteins that tend to change little across viral strains. In their paper published in Proceedings of the National Academy of Sciences, the group describes their approach to developing a new kind of flu vaccine and how well it has worked in test mice.   Because the two main types of flu strains, A and B, adapt so quickly to annual vaccines, new ones have to be developed every year. This approach is not only expensive, but also hit-and-miss—the medical community sometimes encounters a surprise variant that their newly created vaccine cannot fight. Because of that, medical researchers have been looking for a better alternative. In this new effort, the researchers built on lessons learned from the pandemic. The two main vaccines developed to protect people against COVID-19 are based on messenger RNA technology (mRNA), in which pieces of genetic code are administered, prompting the immune system to produce proteins that target the SARS-CoV-2 virus should it appear.

To develop a similar type of vaccine for influenza, the researchers used multiple bits of genetic code to get the body to produce antigens for matrix protein 2, the stalk part of hemagglutinin, nucleoprotein and neuraminidase. The team then tested their vaccine on mice, none of which had ever been infected by the influenza virus. In all, 20 mice were injected with combinations of the new vaccine. Some were injected with a vaccine for just two of the mRNA segments, for example, while others got all four. They also injected some of the mice more than once. Blood testing showed that all of the mice produced some degree of an increase in antibody production, but only the mice who got the quadrivalent shot were fully protected, though there was one exception—the mice that got a monovalent vaccine with just nucleoprotein. The researchers also found that some of the combinations led to an increase in production of cytotoxic T cells, which prior research has shown play a major role in combating flu infections in both mice and humans.

Research cited published in P.N.A.S. (Nov. 2, 2022):

https://doi.org/10.1073/pnas.2206333119 

In 2009, global health officials started tracking a new kind of flu. It appeared first in Mexico, in March, and quickly infected thousands. Influenza tends to kill the very young and the very old, but this flu was different. It seemed to be severely affecting otherwise healthy young adults. American epidemiologists soon learned of cases in California, Texas, and Kansas. By the end of April, the virus had reached a high school in Queens, where a few kids, returning from a trip to Mexico, had infected a third of the student body. The Mexican government closed its schools and banned large gatherings, and the U.S. considered doing the same. “It was a very scary situation,” Richard Besser, who was then the acting director of the Centers for Disease Control and Prevention, told me. Early estimates suggested that the “swine flu,” as the new strain became known, killed as many as fourteen per cent of those it infected—a case fatality rate more than two hundred times higher than typical seasonal flu. The virus soon spread to more than a hundred and fifty countries, and the Obama Administration considered delaying the start of school until after Thanksgiving, when a second wave could be under way. Manufacturers worried about vaccine supplies. Like most flu vaccines, the one for the swine flu was grown in chicken eggs. “Even if you yell at them, they don’t grow faster,” Tom Frieden, who replaced Besser as the director of the C.D.C., said, at a press conference.

In the end, the world got lucky. The early stats were misleading: although swine flu was extremely contagious, it wasn’t especially deadly. Sometimes the reverse is true. Avian flu, which spread across the world during the winter of 2005-06, is not particularly transmissible but is highly lethal, killing more than half of those it infects. Each flu virus has its own epidemiological profile, determined by its genetic makeup, and flu genes shift every year. Howard Markel, a physician and historian of epidemics who, in the early two-thousands, helped invent the concept of “flattening the curve,” compared influenza’s swappable genetic components to “two wheels of fortune.” A double whammy—ease of spread combined with lethality—could make covid-19, or even the 1918 flu, which killed between forty million and a hundred million people, look like a twenty-four-hour bug.

After the swine flu’s relatively harmless nature became apparent, many people asked if the alarm it provoked had been warranted. A Swiss survey found that trust in institutions had decreased. Some scientists and officials accused the World Health Organization of stirring up a “faked” pandemic to justify its budget. But most drew the opposite conclusion from the experience. Trying to prepare for a deadly flu pandemic had left them more alarmed. “There was just a sense of overwhelming relief,” Besser said. “If this had been like 1918, we sure weren’t ready.” In truth, we’re never fully ready for the flu. We know it’s coming, like the first fall leaf, and yet three times in the past century—in 1918, 1957, and 1968—it has flattened us, killing a million or more each time. Even in ordinary years, the disease infects a billion people around the world, killing hundreds of thousands; one study estimated that it costs the United States economy close to a hundred billion dollars annually. Our primary weapon against the virus, the flu vaccine, is woefully inadequate. Over the last decade and a half in the United States, flu vaccines have prevented illness only forty per cent of the time; in particularly bad years, when vaccines were less fine-tuned to the strains that were circulating, they were only ten-per-cent protective. Today, the coronavirus pandemic is rightfully the object of our most strenuous efforts. And yet, as the infectious-disease specialists David Morens, Jeffrey Taubenberger, and Anthony Fauci wrote, in a 2009 article in The New England Journal of Medicine, that “we are living in a pandemic era that began around 1918,” when the flu used shipping networks to traverse the world. Since the 1918 pandemic, this century-long, multi-wave pandemic has killed roughly the same number of people.....

Covid suppression measures may have solved the headache of correctly formulating flu shots to match a winter's dominant influenza strain. In the eight years leading up to the Covid-19 pandemic, one of the subtypes of influenza A viruses started acting bizarrely. Flu viruses continuously evolve, to evade the immune defenses humans develop to fend them off. But after 2012, H3N2 started to behave differently.  It was almost as if there was a falling out within a family. The viruses formed into factions — clades, in virologists’ language — drifting further and further apart with each passing year and making the process of choosing the version of H3N2 to include in flu shots an increasingly challenging task. The greater the genetic distance between the clades, the bigger the cost of making the wrong choice. Vaccine that protects reasonably well against one might perform poorly if the other turned out to be the dominant strain in a given winter. In fact, that’s precisely what happened in the 2017-18 season, when the flu shot failed to protect three-quarters of vaccinated people in the U.S. against the H3N2 strain in circulation.  But an unexpected upside of the Covid-19 pandemic may have solved this problem for us — or at least made flu’s diversity more manageable. With Covid suppression measures like mask wearing, school closures, and travel restrictions driving flu transmission rates to historically low levels around the world, it appears that one of the H3N2 clades may have disappeared — gone extinct. The same phenomenon may also have occurred with one of the two lineages of influenza B viruses, known as B/Yamagata. Neither has been spotted in over a year. In fact, March of 2020 was the last time viral sequences from B/Yamagata or the H3N2 clade known as 3c3.A were uploaded into the international databases used to monitor flu virus evolution, Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle, told STAT.

If the global pool of flu viruses has truly shrunk to this degree, it would be a welcome outcome, flu experts say, making the twice-a-year selection of viruses to be included in flu vaccines for the Northern and Southern hemispheres much easier work.  “I think it has a decent chance that it’s gone. But the world’s a big place,” Bedford said of the H3N2 clade that may have disappeared. Florian Krammer, a flu expert at Mount Sinai School of Medicine in Manhattan, has been scouring genetic databases looking for B/Yamagata viruses. He’s hoping the viruses in this lineage are gone for good. “Just because nobody saw it doesn’t mean it has disappeared completely, right? But it could,” Krammer said. Flu is complex and a brief primer might be helpful here. There are two key families that cause human disease, influenza A and influenza B. Two subtypes of flu A viruses currently transmit among people, H1N1 and H3N2. Within those two subtypes are subclassifications or clades, with H3N2 viruses having more diversity than H1N1. Flu B doesn’t have subtypes, but its viruses divide into two “lineages”, B/Victoria and B/Yamagata. In the not-too-distant past only one of the B viruses was included in flu shots every year, but now most brands are quadrivalent — four-in-one shots that include one version each of the H1N1 and H3N2 viruses, and both flu B viruses. “We work so hard to get quadrivalent vaccines … and now, if really Yamagata has disappeared, then actually trivalent [vaccine] would be okay again,” said Ben Cowling, a flu expert at Hong Kong University. For the record, Cowling is among the skeptics when it comes to the question of whether B/Yamagata is actually gone.  So is Cécile Viboud, a flu epidemiologist at the National Institutes of Health’s Fogerty International Center.  “It’s hard to rule out,” Viboud said, adding these viruses could be circulating at low levels in places that didn’t use the types of non-pharmaceutical interventions like mask wearing and social distancing that other countries have employed to suppress Covid transmission. “The world is a very big place.”

The measures used to slow the spread of Covid-19 have had a dramatic impact on transmission of a number of respiratory viruses. Flu, respiratory syncytial virus — known as RSV — and many of the other bugs that afflict us during cold and flu season have been mercifully absent during the pandemic.  During a typical year, the genetic sequences of about 20,000 flu viruses are logged into GISAID, a repository used by researchers and public health officials to monitor the evolution of influenza and coronaviruses. But in the past year, only 200 were uploaded, Bedford said. Part of that is likely due to the fact that labs that do viral sequencing are prioritizing work on SARS-CoV-2, the virus that causes Covid. But a big factor here is that there is just a lot less flu transmission occurring, around the globe. That has led to a substantial winnowing of the pool of human flu viruses. “There had been maybe five-ish, six-ish [H3N2] clades circulating and now there’s two or three that made it through that bottleneck,” Bedford said. Though there’s been little flu illness globally, there are places that have seen outbreaks during the pandemic, he noted, saying China recorded flu B transmission — the Victoria lineage — and West Africa, Bangladesh, and Cambodia had H3N2 activity. Richard Webby, director of the World Health Organization Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds, cautioned that only a portion of flu viruses ever undergo genetic sequencing, so predictions about which flu viruses may have disappeared that are based on what’s in the databases risk being wrong.

But Webby does believe there has been a large reduction in the diversity of the circulating flu viruses, saying it will be interesting to see how that plays out in coming years. “Without doubt this is definitely going to change something in terms of the diversity of flu viruses out there. The extent to which it changes and how long it stays changed are the big question marks. But we have never seen this before,” said Webby, whose center is based at St. Jude Children’s Hospital in Memphis. His bet is that the B/Yamagata viruses aren’t gone, noting the flu B virus lineages sometimes go quiet for a while, only to reappear later. “But I do think we’re likely to lose a little bit of the H3N2 diversity. That’s a great thing.  Currently when we sit down to make recommendations for vaccine strains, it’s always the headache virus,” Webby said. “If we have to pick a [subtype] to lose diversity in, that would be the one.”

(HealthDay)—Influenza vaccination may have a protective effect for COVID-19-positive patients, according to a brief report recently published in the Journal of the American Board of Family Medicine. Ming-Jim Yang, M.D., from the University of Florida in Gainesville, and colleagues conducted a retrospective review involving 2,005 patients older than 18 years of age who tested positive for COVID-19. Influenza vaccination status and comorbidities were examined. Severity of disease as reflected by hospitalization and intensive care unit (ICU) admission was examined as the primary outcome. The association between influenza vaccination status and hospitalization was examined. The researchers found that compared with those who were vaccinated, COVID-19-positive patients who had not received the influenza vaccine within the last year had 2.44- and 3.29-fold increased odds of hospitalization and ICU admission, respectively. The results were adjusted for age, race, gender, hypertension, diabetes, chronic obstructive pulmonary disease, obesity, coronary artery disease, and congestive heart failure. "One of the biggest problems we have with any preventive measure is getting people to do it," a coauthor said in a statement. "So, maybe this would be a pretty good push for people to go out and get their flu shot."

Study published in JABFM:

https://www.jabfm.org/sites/default/files/COVID_20-0528.pdf

Researchers at Georgia State University.develop universal flu vaccine that protects against six influenza viruses in mice. The researchers developed and showed that a novel nanoparticle vaccine that combines two major influenza proteins is effective in providing broad, long-lasting protection against the influenza virus in mice, showing promise as a universal flu vaccine. Findings from the new study—performed in mice and published recently in Advanced Healthcare Materials through an article titled “Double‐Layered M2e‐NA Protein Nanoparticle Immunization Induces Broad Cross‐Protection against Different Influenza Viruses in Mice”—suggest this unique vaccine combination has potential as a universal influenza vaccine or component of such vaccines.

The double-layered nanoparticle vaccine contains the influenza virus proteins matrix protein 2 ectodomain (M2e) and neuraminidase (NA). Mice were immunized with the nanoparticle vaccine before being exposed to the influenza virus, and they were protected against six different strains of the virus. “This nanoparticle antigen combination conferred mice with strong cross-protection,” explained lead study investigator Ye Wang, a doctoral candidate at the Institute for Biomedical Sciences. “It can protect mice from different strains of influenza virus. Each season, we have different flu strains that affect us. By using this approach, we hope this nanoparticle vaccine can protect humans from different strains of the influenza virus.”

Influenza is a leading cause of death by infection. Seasonal flu vaccines are insufficient to prevent influenza outbreaks and developing a universal influenza vaccine is the ideal strategy for eliminating public health threats of influenza epidemics and pandemics. A universal influenza vaccine would eliminate the need for vaccinations each season and offers universal protection against all influenza strains. The influenza virus protein M2e is found in all influenza virus strains, with each strain having a very similar version, and the protein has mutated very slowly over time. The protein NA is found on the surface of the influenza virus and has also mutated much slower than other influenza proteins. This double-layered nanoparticle vaccine uses M2e as its core, and NA is coated on the surface. In the current study, mice were exposed to one of six influenza virus strains after receiving the nanoparticle vaccine by intramuscular injection. The vaccine proved to have long-lasting immune protection, which was unchanged against viral challenges up to four months after immunizations. 

Published in Advanced Healthcare Materials (Dec. 15, 2019):

https://doi.org/10.1002/adhm.201901176

Toward the end of last year’s flu season — in about the middle of winter — flu experts noticed that the number of infections was not dropping, but picking up. A new virus seemed to be emerging, and it was making many Americans sick.  The virus was a type of H3N2 strain, and it started rapidly spreading among people in the United States before spreading into Europe, Canada, and South America. This put scientists worldwide who are tasked with determining what’s in the yearly flu vaccine on high alert. Did the flu vaccine for the 2019–2020 flu season need to be updated to protect against this new virus strain? The next flu season was still many months away, but it was time to scramble.

“Almost every year there is some kind of challenge,” says Dr. David Wentworth, a leading flu expert and chief of the U.S. Centers for Disease Control and Prevention’s (CDC) Virology, Surveillance, and Diagnosis Branch. “The thing about the flu is you have to be nimble.” One of the trickiest tasks for public health experts worldwide is creating the annual flu vaccine. The number of people who get sick from the flu each year depends largely on how well scientists predict what strains of the flu will be circulating and match them with a successful vaccine. “The flu virus evolves so fast,” says Wentworth. “It’s important to update the vaccine when it changes significantly enough to warrant it.”

The process of identifying the “right” viruses and producing enough flu vaccine for the nation starts with year-round study of flu viruses globally and ends with millions of Americans being vaccinated, the CDC says. While the effectiveness of each year’s flu vaccine can vary, the vaccine still prevents millions of illnesses, tens of thousands of hospitalizations, and thousands of deaths every year in the United States. And this year, the new vaccine does contain a new H3N2 strain. Flu experts worldwide, Wentworth says, are always prepared for the unpredictable. “We get kind of used to it with influenza because there are a lot of curveballs you need to respond to very rapidly,” he says. Wentworth and the CDC’s flu team led Elemental through their process for making this season’s flu vaccine.

How well the flu vaccine works in a given year depends partly on the match between the viruses used to make the vaccine and the viruses spreading among people during a given flu season. That’s why a year ago flu researchers started considering the newer H3N2 strain for this year’s vaccine. In fact, Wentworth and his team are already thinking about the vaccine for the 2020–2021 flu season.

A team of researchers from the Yale School of Public Health, the University of Maryland School of Medicine, the University of Texas and the University of Florida has used math models to show that the development of a universal influenza vaccine could save tens of thousands of lives annually. In their paper published in Proceedings of the National Academy of Sciences, the group describes how they used mathematical modeling to evaluate the impact of a universal flu vaccine and what they found.

Every year, millions of people in the U.S. become infected and tens of thousands die from flu. And as the researchers note, the efficacy of flu vaccines is approximately 44 percent—leaving a significant number of people at risk of being infected, even if they get a shot. They note also that the National Institute of Allergy and Infectious Diseases in the U.S. recently announced that a universal vaccine with an efficacy rate of approximately 75 percent had been developed, sparking hopes of greatly reducing flu infections. They further note that the U.S. government has pledged more than a billion dollars to subsidize the development of a universal vaccine that would be one hundred percent effective. In this new effort, the researchers have created and used models to show how many people would be spared infections and how much money would be saved if such a vaccine were developed and used.

The researchers report that the models showed that if just 10 percent of current vaccinations were replaced with a universal vaccine, there would be approximately 5.3 million fewer people infected each year and approximately 6,300 fewer death, and that there would be over a billion dollars saved in healthcare expenses. The team also reports that if all current vaccinations were replaced with a universal vaccine, there would be 17 million fewer infections and 19,500 fewer deaths. And the cost savings would average approximately $3.5 billion each year. They note that infection and death rate changes would vary by state as would the cost savings. But they conclude, the savings in healthcare costs related to treating influenza patients would far outweigh the amount the government has pledged to find a universal vaccine.

Findings published on Sept. 23, 2019 in P.N.A.S.:

https://doi.org/10.1073/pnas.1909613116

Researchers at UC Riverside have developed a new vaccine approach using RNA that is effective against any strain of a virus and can be used safely even by babies or the immunocompromised. Every year, researchers try to predict the four influenza strains that are most likely to be prevalent during the upcoming flu season. And every year, people line up to get their updated vaccine, hoping the researchers formulated the shot correctly. The same is true of COVID vaccines, which have been reformulated to target sub-variants of the most prevalent strains circulating in the U.S. This new strategy would eliminate the need to create all these different shots, because it targets a part of the viral genome that is common to all strains of a virus. The vaccine, how it works, and a demonstration of its efficacy in mice is described in a paper published today in the Proceedings of the National Academy of Sciences.

“What I want to emphasize about this vaccine strategy is that it is broad,” said UCR virologist and paper author Rong Hai. “It is broadly applicable to any number of viruses, broadly effective against any variant of a virus, and safe for a broad spectrum of people. This could be the universal vaccine that we have been looking for. Traditionally, vaccines contain either a dead or modified, live version of a virus. The body’s immune system recognizes a protein in the virus and mounts an immune response. This response produces T-cells that attack the virus and stop it from spreading. It also produces “memory” B-cells that train your immune system to protect you from future attacks. The new vaccine also uses a live, modified version of a virus. However, it does not rely on the vaccinated body having this traditional immune response or immune active proteins — which is the reason it can be used by babies whose immune systems are underdeveloped, or people suffering from a disease that overtaxes their immune system. Instead, this relies on small, silencing RNA molecules.

Mechanism and Efficacy of RNA-Based Vaccine

“A host — a person, a mouse, anyone infected— will produce small interfering RNAs as an immune response to viral infection. These RNAi then knock down the virus,” said Shouwei Ding, distinguished professor of microbiology at UCR, and lead paper author. The reason viruses successfully cause disease is because they produce proteins that block a host’s RNAi response. “If we make a mutant virus that cannot produce the protein to suppress our RNAi, we can weaken the virus. It can replicate to some level, but then loses the battle to the host RNAi response,” Ding said. “A virus weakened in this way can be used as a vaccine for boosting our RNAi immune system.” When the researchers tested this strategy with a mouse virus called Nodamura, they did it with mutant mice lacking T and B cells. With one vaccine injection, they found the mice were protected from a lethal dose of the unmodified virus for at least 90 days. Note that some studies show nine mouse days are roughly equivalent to one human year.

There are few vaccines suitable for use in babies younger than six months old. However, even newborn mice produce small RNAi molecules, which is why the vaccine protected them as well. UC Riverside has now been issued a US patent on this RNAi vaccine technology. In 2013, the same research team published a paper showing that flu infections also induce us to produce RNAi molecules. “That’s why our next step is to use this same concept to generate a flu vaccine, so infants can be protected. If we are successful, they’ll no longer have to depend on their mothers’ antibodies,” Ding said.  Their flu vaccine will also likely be delivered in the form of a spray, as many people have an aversion to needles. “Respiratory infections move through the nose, so a spray might be an easier delivery system,” Hai said. Additionally, the researchers say there is little chance of a virus mutating to avoid this vaccination strategy. “Viruses may mutate in regions not targeted by traditional vaccines. However, we are targeting their whole genome with thousands of small RNAs. They cannot escape this,” Hai said. Ultimately, the researchers believe they can ‘cut and paste’ this strategy to make a one-and-done vaccine for any number of viruses. “There are several well-known human pathogens; dengue, SARS, COVID. They all have similar viral functions,” Ding said. “This should be applicable to these viruses in an easy transfer of knowledge.”

Publised in PNAS (April 17, 2024):

https://doi.org/10.1073/pnas.2321170121

The BCCDC says this year's vaccine appears to cut the risk of medically attended influenza-like illness by more than half, with an estimated vaccine effectiveness of 55 per cent. The BC Centre for Disease Control says early evaluation shows this year’s influenza vaccine formula is providing “substantial” protection against the wave of flu so far. “The earlier-than-usual influenza epidemic this season has enabled us to assess vaccine effectiveness earlier than usual,” BC CDC epidemiologist and Canadian Sentinel Practitioner Surveillance Network lead Dr. Danuta Skowronski said. “We will update our analyses in the new year, but these interim findings show a substantial reduction in the risk of influenza illness for vaccinated people who seek medical care.” Analysis for the period from Nov. 1 to Dec. 14 with samples from B.C., Alberta, Ontario and Quebec had cut the risk of medically attended influenza-like illness by more than half, with an estimated vaccine effectiveness of 55 per cent. An update from the BCCDC on Thursday also showed there had been no additional flu-related deaths among children and youth this season. Six people under the age of 18 have died so far this year, several due to suspected influenza-linked bacterial infections. That same update showed that the epidemic wave appears to be waning. About 16 per cent of samples over the week ending Dec. 17 came back positive — down from a high of 27 per cent during the week ending Nov. 26.

The BCCDC’s latest analysis shows the number of tests that came back positive for RSV for the week ending Dec. 17 jumped to 13 per cent, up from six per cent in the week ending Nov. 26. Test-positivity for both RSV (37 per cent) and influenza A (21 per cent) remains higher among children and youth younger than 18 than in the general population, the BCCDC said. According to the BCCDC, the H3 subtype of influenza A remains the dominant strain of influenza this year, accounting for more than 90 per cent of tested samples. The H3N2 subtype is often linked to more severe outbreaks and lower vaccine effectiveness, however, this year’s vaccine appears to be as good as or better than in previous years the subtype was dominant, the agency said. “Vaccine protection is especially important for people at higher risk of severe complications and for a health-care system that is managing the circulation of multiple respiratory viruses at the same time as we enter the holiday period,” Skowronski said. The province continues to recommend vaccines for anyone aged six months and older, and is urging anyone who feels unwell to stay home.

US CDC historical data on influenza vaccine effectiveness in past seasons available at: 

https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html 

The vaccine was only about 16 percent effective at reducing a person’s chance of getting a mild or moderate infection, the agency said. Experts said a good rate would be at least 50 percent. This season’s flu vaccine has offered little to no protection against getting a mild or moderate case of influenza, the Centers for Disease Control and Prevention said this week.This season’s flu vaccine has offered little to no protection against getting a mild or moderate case of influenza, the Centers for Disease Control and Prevention said this week. In a study of more than 3,600 Americans in seven states, the C.D.C. said in a report that the vaccine was only around 16 percent effective, a rate that it said was “not statistically significant.” “It’s not ineffective, but it’s clearly suboptimal in its efficacy,” Dr. Jesse L. Goodman, a former chief scientist at the Food and Drug Administration, said on Thursday. He reviewed the report but was not associated with it. Still, despite the vaccine’s lackluster performance this season, which started in October and lasts through May, the C.D.C. suggested that people get inoculated, saying that it could “prevent serious outcomes.”

Scientists had warned in 2020 that the flu season, if it was severe, could possibly converge with Covid to create a dreaded “twindemic.” But coronavirus restrictions — including working from home and the use of masks — along with a high flu vaccine rate may have helped reduce caseloads the last few seasons, during which, the C.D.C. said, cases have been at a record low. Still, even a mild flu season can be devastating. The C.D.C. estimated that during the 2019-20 flu season, around 22,000 people in the country had died and 400,000 had been hospitalized. This season, the agency said, “influenza activity” declined in December and January, during the worst of the Omicron surge, but increased in early February. In October and November of 2021, the agency investigated a flu outbreak at the University of Michigan, where there were 745 cases, mostly involving students who had not been vaccinated against the flu. Investigators there also found that the vaccine did not offer much protection. Dr. Goodman said that this season’s results showed how much flu vaccines could be improved.

“The next pandemic could be an influenza pandemic,” Dr. Goodman said, “so we need better vaccines.” Every year, scientists decide whether they need to update the flu vaccine to protect against the strains that they predict will dominate the upcoming season. The low efficacy rate this season, Dr. Goodman said, “suggests that there was a mismatch between the strains of virus in the vaccine and what’s circulating.” Scientists updated this season’s vaccines to offer protection against four flu viruses, including H3N2, which ended up being this season’s dominant strain, the report said. H3N2 was also dominant during the 2017-18 flu season, which experts had said was “moderately severe.” Since the agency began calculating the vaccine’s effectiveness in 2004, the efficacy rate has been as high as 60 percent — for the 2010-11 season — and as low as 10 percent, during the first season the C.D.C. tracked it. Dr. Goodman said he would consider a rate between 50 and 80 percent to be good. The flu is a life-threatening respiratory illness that can fill up hospital beds. It shares symptoms with Covid, including fever, coughing, a sore throat and fatigue. Adults 65 and older, those who are pregnant or immunocompromised and children under 5 are most at risk of the flu.

CDC report (March 11, 2022) available at:

https://www.cdc.gov/mmwr/volumes/71/wr/mm7110a1.htm 

Vaccine makers are betting that the mRNA technology powering two successful Covid vaccines will help curb the tragic global death toll from the flu.  As the world grapples with Covid-19, influenza isn’t getting much attention these days. But the flu’s global impact is staggering: three million to five million cases of severe illness every year, and up to 650,000 deaths. Every few decades, a new flu strain spills over from animals and leads to a pandemic. The deadly toll of influenza is all the more striking when you consider that we have had vaccines to fight it for eight decades. But they remain mediocre. A flu shot is good for only one flu season, and its effectiveness typically reaches somewhere between 40 and 60 percent. In some years it’s as low as 10 percent. But a new generation of highly effective flu vaccines may emerge in the next few years, based on the same mRNA technology that has protected hundreds of millions of people against Covid-19. While traditional influenza vaccines are grown for months in chicken eggs, mRNA vaccines are manufactured relatively quickly from scratch. In theory, their faster production may make them better matched to each season’s flu strains. And when they’re injected into people, they may provoke a stronger immune response than traditional flu vaccines do.

Two companies — Moderna, the Massachusetts biotech company that produced one of the authorized mRNA vaccines for Covid-19, and Sanofi, a French vaccine maker — began trials for mRNA flu vaccines this summer. Pfizer and BioNTech, the companies that produced the other mRNA Covid-19 vaccine, started their own flu trial last month. And Seqirus, a vaccine producer based in England, is planning to test another mRNA vaccine for the flu early next year.  No one can say for sure how well any of these four seasonal flu vaccines will turn out, but many experts are optimistic. And further down the line, mRNA technology may be tailored to make vaccines that work for years against a wide range of influenza strains. “I am beyond excited for the future of flu vaccination,” said Jenna Bartley, an immunologist at the University of Connecticut. No one can say for sure how well any of these four seasonal flu vaccines will turn out, but many experts are optimistic. And further down the line, mRNA technology may be tailored to make vaccines that work for years against a wide range of influenza strains. “I am beyond excited for the future of flu vaccination,” said Jenna Bartley, an immunologist at the University of Connecticut.

Vaccine aims to elicit broadly protective antibodies against the “stalk” of a surface protein on influenza viruses. For epidemiologists, the COVID-19 pandemic has greatly intensified their long-standing nightmare about another virus: the emergence of a new and deadly strain of flu. A universal flu vaccine, effective against any strain of the influenza virus that can infect humans, could protect us from this peril, but progress has been slow. A novel concept for one universal vaccine candidate has now passed its first test in a small clinical trial, its developers report today in Nature Medicine.  “This is an important paper,” says Aubree Gordon, an epidemiologist at the University of Michigan School of Public Health who studies influenza transmission and vaccines. The influenza virus rapidly accumulates mutations and easily “reassorts,” or swaps, genes between strains, creating variants that can dodge any past immunity people had acquired naturally or from vaccines. That’s why a new flu vaccine must be developed each year.

Existing flu vaccines contain weakened or inactivated influenza viruses with a mix of hemagglutinins (HAs), the proteins that stud their surfaces. These vaccines primarily aim to trigger antibody responses against HA’s top part, or head. Genetic changes in flu viruses rarely alter most of the head. But a small part of the head does reassort, or mutate, frequently, which allows new viral strains to dodge any immune memory and forces flu vaccinemakers to prepare new formulations each year, with updated HAs. HA’s bottom portion, or stalk, is less apt to vary, and epidemiological studies have shown people who have been exposed to an influenza strain and developed antibodies to the stalk can ward off a wide variety of other strains. So, the new universal flu vaccine candidate, one of a handful in development, puts HA’s stalk front and center. The study shows for the first time that “you can develop a vaccine strategy that produces stalk-reactive antibodies in humans,” says virologist Florian Krammer of the Icahn School of Medicine at Mount Sinai, who co-leads a multi-institutional universal flu vaccines consortium funded by the U.S. National Institute of Allergy and Infectious Diseases and helped develop the candidate tested in the new trial. Other clinical trials testing stalk-based universal flu vaccine candidates have yet to report data. Targeting the stalk is harder than it sounds, because immune memory cells built up over a lifetime of flu infections react so strongly to the conserved region of HA’s head that this response overrides production of antibodies against the stalk. Some researchers have tried to make flu vaccines that only contain HA’s stalk, but this fragment is highly unstable. To get around this problem, Krammer and colleagues made what they call chimeric HAs, which link the protein’s conserved stalk to unusual heads that are entirely new to the human immune system and don’t trigger a person’s immune memory. Only low levels of head antibodies are produced, allowing a strong new immune response to stalk to dominate. In essence, the head of the chimera is only there to stabilize the stalk.

Influenza vaccines contain three to four strains of the virus that are classified as group A, which breaks into two other divisions, and group B strains. The researchers developed vaccines made from live, weakened versions of influenza viruses or inactivated viruses bearing chimeric HAs representing only one division of group A. In the trial, 51 participants received the various vaccines and their antibodies were compared with those of 15 people who received placebos. A single shot of vaccine with chimeric HA inactivated viruses, the researchers report, “induced remarkably high antistalk antibody titers.” The trial was only a phase I study to establish safety and measure immune responses, which means it didn’t test the ability of the vaccines to protect people from influenza. Still, when the researchers transferred human antibodies triggered by the experimental vaccines into mice and then “challenged” the rodents with the influenza virus, the mice lost far less weight than untreated mice who also were infected, suggesting the antibodies protected them. Immunologist James Crowe, who runs the vaccine center at Vanderbilt University, says the study is “a serious effort” to test the stalk antibody hypothesis and “an important first step.”  Krammer says it will likely take at least 2 years to develop chimeric HAs representing enough other strains from influenza groups A and B to be combined into a universal vaccine. That mix would then be tested in a large-scale, multiyear study designed to show that the vaccine candidate works better than the seasonal vaccine. The seasonal vaccine works fairly well in years when its HA closely matches the variants in circulation, so the chimeric HAs would only show their true power during one of the rarer years when there’s a mismatch. This “long development path,” Krammer suspects, is the main reason his team lost an initial corporate partner, GlaxoSmithKline, which has another universal flu vaccine in clinical trials. “It’s difficult to get to get a lot of interest for something like this,” Krammer says.

Cited Research Published in Nat. Medicine (Dec. 7, 2020):

https://doi.org/10.1038/s41591-020-1118-7

Fully vaccinating children reduced the risk of hospitalization for complications associated with influenza by 54%, according to a new study by Ben-Gurion University of the Negev (BGU) and University of Michigan researchers. The research, published in the December, 2019 print journal Clinical Infectious Disease, is one of the few studies worldwide that has tested the effectiveness of childhood vaccination against influenza and risk of hospitalization due to the influenza complications. The study was led by Dr. Hannah Segaloff, an epidemiologist at the School of Public Health, University of Michigan and Prof. Mark Katz, M.D., of BGU's Department of Health Management, Faculty of Health Sciences and a senior researcher at the Clalit Institute of General Research. Prof. Katz also teaches in BGU's Medical School for International Health.

The retrospective study reviewed the vaccination data of 3,746 hospitalizations of children ages six months to 8 years old at six hospitals in Israel. They were tested for influenza over three winter seasons 2015-16, 2016-17 and 2017-18. The findings reveal that the flu vaccine reduced hospitalizations associated with the flu by more than half. They also validate guidelines in the United States and Israel that recommend two vaccine doses for children up to age 8 who have never been vaccinated or who previously received one dose. "Children vaccinated according to government guidelines are much better protected from influenza than those who only receive one vaccine," says Dr. Segaloff. "Over half of our study population had underlying conditions that may put them at high risk for severe influenza-related complications, so preventing influenza in this group is critically important.

Published in Clinical Infectious Diseases:

https://doi.org/10.1093/cid/ciz125

The influenza (flu) vaccine can not only prevent illness that may cause a week or more of misery, it can reduce the likelihood of hospitalization in children and death in adults, according to two analyses of Centers for Disease Control and Prevention (CDC)-supported U.S. influenza surveillance data being presented at IDWeek 2019.  The first study supports the benefit of flu vaccination in preventing severe outcomes in children. Children who received the influenza vaccine were half as likely to be hospitalized with flu as those who didn’t get vaccinated, according to the study, which followed more than 3,600 children over two seasons. The second study looked at more than 43,000 older adults hospitalized with flu over five seasons and found that vaccination reduced the risk of severe outcomes – including death, pneumonia, intensive care admission and mechanical ventilation – by more than one-third.

“These studies add to the evidence that influenza vaccines prevent serious complications from flu,” said Angela P. Campbell, MD, MPH, FIDSA, FPIDS, lead author of the study in children and medical officer in the Epidemiology and Prevention Branch of the Influenza Division at the CDC, Atlanta. “They show just how important it is that everyone six months and older who is eligible to get a flu vaccine does so every year.”

Flu vaccination in children reduces risk of hospitalization

In the first study, conducted by seven pediatric medical centers comprising the New Vaccine Surveillance Network, researchers analyzed flu test results from 3,630 children, aged 6 months to 17 years old, who were hospitalized with acute respiratory illness over two flu seasons in which influenza A(H3N2) viruses were the predominantly circulating virus. Patients were tested for influenza using molecular diagnostic tests: 163 out of 1,714 (10%) during the 2016-2017 season and 218 out of 1,916 (11%) during the 2017-2018 season tested positive for flu, including A(H3N2), A(H1N1) and B viruses. Researchers estimated how well the flu vaccine worked to reduce hospitalizations due to laboratory-confirmed influenza by comparing the frequency of flu vaccination among children who tested positive for flu to vaccination among children without flu, adjusting for age, race/ethnicity, enrollment month, study site and underlying medical conditions. Based on this information, the vaccine effectiveness against influenza-associated hospitalizations was 50% over the two seasons (49% for the first season and 51% the second), meaning that vaccination reduced the risk of hospitalization with flu by about half. “This is encouraging given that flu vaccines often work better against H1N1 and B flu viruses than against H3N2 viruses,” said Dr. Campbell. “Our findings support the use of vaccination to prevent severe flu illness in children during every flu season, regardless of which viruses are predominant.”

Flu vaccination in adults reduces risk of death

In the second study, researchers looked at five flu seasons using the U.S. Influenza Hospitalization Surveillance Network and identified 43,608 adults (18 and older) hospitalized with laboratory-confirmed flu. Overall, 38% of those 18 to 64 years old and 65% of those 65 or older had received a flu vaccine. Researchers assessed vaccination status among hospitalized patients to determine the reduction in the odds of severe outcomes among vaccinated patients compared to those who were unvaccinated. The findings showed that in patients diagnosed with influenza A(H1N1), flu vaccination reduced their odds of severe outcomes, including death, by 36%. Severe outcomes included death, pneumonia, admission to the intensive care unit and mechanical ventilation.

Flu vaccination in adults 18-64 with A/(H1N1) influenza was associated with reduced risk of the following: 36% death, 17% pneumonia, 19% intensive care unit (ICU) admission and 34% mechanical ventilation. Vaccination also was associated with a shorter ICU length of stay. Flu vaccination in those 65 years or older was associated with reduced risk of the following: 28% ICU admission, 46% mechanical ventilation. It was also associated with a shorter hospital length of stay.....

In 2017, a terrible flu season in Australia presaged an American outbreak in which 79,000 died. Experts advise getting the shot soon. Australia had an unusually early and fairly severe flu season this year. Since that may foretell a serious outbreak on its way in the United States, public health experts now are urging Americans to get their flu shots as soon as possible.

“It’s too early to tell for sure, because sometimes Australia is predictive and sometimes it’s not,” said Dr. Daniel B. Jernigan, director of the influenza division of the Centers for Disease Control and Prevention. “But the best move is to get the vaccine right now.” The number of cases of flu in this country is still quite low, according to the weekly C.D.C. FluView released Friday. But as the weather cools, it is expected to ramp up. In 2017, Australia suffered its worst outbreak in the 20 years since modern surveillance techniques were adopted. The 2017-2018 flu season in the United States, which followed six months later as winter came to the Northern Hemisphere, was one of the worst in modern American memory, with an estimated 79,000 dead. 

This year’s Australian outbreak began in April, two months earlier than usual, and persisted into October. Alarming early reports  said the number of deaths might surpass those in 2017, but that did not quite happen. (The country did have more positive flu tests than ever before, but that was in part because far more tests were performed.). Nonetheless, there were more flu-related deaths than usual, while hospitalization rates and nursing home outbreaks “were at moderate to high levels,” said  Ian Barr, deputy director of World Health Organization Collaborating Center for Reference and Research on Influenza in Melbourne.  Direct comparisons of mortality rates are difficult, because Australia counts only deaths in which a hospital declares influenza the cause; there were 662 this year, and 745 in 2017. Not only is the United States population 13 times bigger, but the C.D.C. — aware that flu triggers even more deaths from pneumonia, sepsis, heart attack and other illnesses — looks at the increased death rates from many illnesses in bad flu years, and calculates how many were probably due to influenza.

At the peak of the 2017-2018 season, the C.D.C. estimated that more than 56,000 Americans would die. Officials later calculates that  79,000 had— which, the agency noted, is more people than usually fill a Super Bowl stadium.  In 2017, Australia’s deadly season set off alarm bells in Britain, where tabloids featured headlines about the "killer Aussie flu".  But no such dire warnings were issued to Americans, in part because of turmoil at the C.D.C. and its parent agency, the Department of Health and Human Services. 

Last month, Dr. Price’s successor, Alex M. Azar II, also got a flu shot on camera at a news conference   that National Foundation for Infectious Diseases holds every year to urge Americans to get vaccinated. Mr. Azar — who stayed through the question and answer session — made it clear that the Trump administration is firmly behind vaccination......