Ha G186v/l194p Double Mutant Disrupts The Rbs
With the knowledge that HA mutations G186V and L194P exert an opposing structural effect on the RBS and that the HA G186V/L194P double mutant was highly deleterious to the virus , we were interested in examining the structural effect of the HA G186VL194P double mutant. Of note, the HA G186V/L194P double mutant abolishes virus replication but not HA protein expression. We were therefore able to recombinantly express and purify the Bris07 HA G186V/L194P double mutant. Crystal structures of the Bris07 HA G186V/L194P double mutant were determined at 2.25 Ã, 2.1 Ã, and 2.4 Ã for the apo form, in complex with 3â²SLNLN, and in complex with 6â²SLNLN, respectively. In all three structures, the electron density for the 190-helix was very weak to absent compared to that of the Bris07 HA L194P single mutant , whose structure was previously determined in the same crystallization condition . This observation indicates that the 190-helix in Bris07 HA G186V/L194P double mutant is extremely disordered. Consistently, the electron density for the receptor analogs 3â²SLNLN and 6â²SLNLN was also very weak in the complex with the Bris07 HA G186V/L194P double mutant. This structural analysis shows that combining HA mutations G186V and L194P dramatically destabilizes the 190-helix, causing a disruption of the RBS and also of antigenic site B, which is the major antigenic site in recent H3N2 viruses .
Electron Density of the 190-Helix
Why You Need A Flu Vaccine In 2021
Experts are expecting the worst from the 2021-2022 flu season. Flu rates were unusually low last winter, in large part because most people were wearing masks, social distancing, and staying home when feeling sick to prevent the COVID-19 pandemic from getting any worse. But with many people returning to society, and a good portion of them without masks, the flu season could come back with a vengeance this season. The early and strong return of RSV is one sign of this.
Without exposure to the flu last year, people may be more vulnerable than usual this season. Because of this, its crucial to get your flu shot.
If youve taken steps to prevent your kid from getting the coronavirus, youd be hypocritical not to do the same for the flu. So far, 655 children aged 17 and below have died from COVID in 2020 and 2021 combined, according to the Centers for Disease Control and Prevention . In comparison, 199 kids were reported to the CDC to have died from flu during the 2018-2019 flu season alone, and statistical modelling suggests that 434 children may have actually died from the flu that season.
So if you worried at all about your kids during the pandemic, you should make sure they get the flu shot. You should get it too, because the flu kills thousands of adults aged 18-49 each year and sends tens of thousands to the hospital . Theres very little point in avoiding getting COVID during a global pandemic just to get knocked out by the seasonal flu.
G186v And L194p Lead To Differences In Receptor
To understand how G186V influences receptor binding, crystal structures of IVR-165 HA in complex the with avian receptor analog NeuAcÎ±2-3GalÎ²1-4GlcNAcÎ²1-3GalÎ²1-4GlcNAc and the human receptor analog NeuAcÎ±2-6GalÎ²1-4GlcNAcÎ²1-3GalÎ²1-4GlcNAc were determined at 2.1 and 2.4 Ã, respectively . When binding to IVR-165 HA, 3â²SLNLN adopts an extended conformation , whereas 6â²SLNLN adopts the canonical folded-back conformation . We also observed a shift of the 220-loop toward the RBS during receptor binding , which is a typical feature of recent human H3 viruses . Similar to our previous observation with Bris07 L194P HA , IVR-165 HA had negligible binding to the glycan array . Of note, the glycan array has more stringent requirements for the detection of receptor binding than the X-ray structure analysis here, which involves soaking the crystals in a 100-fold molar excess of the receptor analogs. Being able to observe electron density for the receptor analogs in our crystal structures but no signal in the glycan array experiments indicates very weak binding to the receptor. This result also substantiates the notion that efficient replication of human influenza virus in chicken eggs does not require strong binding between HA and sialylated receptors .
Structural Analysis of IVR-165 HA in Complex with Glycan Receptor Analogs
The RBS conformations of IVR-165 HA and Bris07 HA-L194P in complex with 6â²SLNLN are compared.
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Table 1 Influenza Vaccines United States 202021 Influenza Season*
|Trade name||HA or virus count for each vaccine virus||Route|
|Standard dose, cell culture based|
|High dose, egg based|
|Fluzone High-Dose Quadrivalent|
|Standard dose, egg based with MF59 adjuvant|
|Standard dose, egg based with MF59 adjuvant|
|0.2-mL prefilled single-use intranasal sprayer||2 through 49 yrs||106.5-7.5 fluorescent focus units/0.2 mL||NAS|
Abbreviations: ACIP = Advisory Committee on Immunization Practices FDA = Food and Drug Administration HA = hemagglutinin IIV3 = inactivated influenza vaccine, trivalent IIV4 = inactivated influenza vaccine, quadrivalent IM = intramuscular LAIV4 = live attenuated influenza vaccine, quadrivalent MDV = multidose vial NAS = intranasal PFS = prefilled syringe RIV4 = recombinant influenza vaccine, quadrivalent SDV = single-dose vial.
* Vaccination providers should consult FDA-approved prescribing information for 202021 influenza vaccines for the most complete and updated information, including indications, contraindications, warnings, and precautions. Package inserts for U.S.-licensed vaccinesexternal icon. Availability and characteristics of specific products and presentations might change and/or differ from what is described in this table and in the text of the full report.
§ The dose volume for Afluria Quadrivalent is 0.25 mL for children aged 6 through 35 months and 0.5 mL for persons aged 3 years.
Can I Get The Flu Vaccine If I Have A Latex Allergy
Influenza vaccines used in Australia dont contain latex and are safe for people with a latex allergy or sensitivity. While the product information for Fluarix Tetra and Fluad Quad state that some presentations of the vaccine cannot be considered latex-free, these presentations are actually not supplied in Australia.
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Delivery Of The Flu Shot In 2021
Not all flu shots are the same. Some arent even shots. Here are your 2021 flu vaccine options:
Nasal Spray: The nasal spray vaccine is the only kind to include a live attenuated influenza vaccine. Although it cant give you the flu, it does have a higher likelihood of inducing flu-like symptoms. This vaccine does not contain thimerosal or other preservatives. Its available only for patients aged 2 to 49.
For: People who cant stand the needle or jet spray or who want to avoid preservatives.
Inactivated shots are usually given with a needle, but Afluria Quadrivalent can be given to adults with a jet injector, which is basically a high-powered spray that penetrates the skin.
For: Needles can be used for everyone aged 6 months and older. The jet spray is approved for adults aged 18 to 64.
Northern Hemisphere Influenza Season
The composition of trivalent virus vaccines for use in the 2017â2018 Northern Hemisphere influenza season recommended by the Advisory Committee on Immunization Practices on August 25, 2017, was:
- an A/Michigan/45/2015 pdm09âlike virus
- an A/Hong Kong/4801/2014 -like virus
- a B/Brisbane/60/2008âlike virus
In addition to these components, quadrivalent vaccines will also include a B/Phuket/3073/2013âlike virus .
In California, some emergency systems were strained by a spike in H3N2 flu cases. In addition, some areas experienced local shortages of oseltamivir. The severity of the flu season seemed somewhat comparable to the 2009â10 swine flu outbreak. A February 2018 CDC interim report estimated the vaccine effectiveness to be 25% against H3N2, 67% against H1N1, and 42% against influenza B.
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Do All Flu Shots Contain Egg Protein
If youre still concerned about egg allergies, there are two flu vaccine brands this year that are completely egg-free: Flucelvax Quadrivalent and Flublok Quadrivalent. They dont contain egg protein because they are made using newer manufacturing processes that dont require growing flu viruses inside of eggs.
Comparing 5 Vaccine Formulations
The retrospective cohort study included more than 13 million seniors ages 65 and older who received one of five flu vaccine formulations last season: Flucelvax , egg-based quadrivalent , egg-based high-dose, adjuvanted, and standard-dose vaccines. The last three versions are all trivalent .
Though an earlier study suggested that the cell-based recombinant vaccine produced in insect cells was more effective than standard egg-based vaccines, it wasn’t evaluated in the study, because it wasn’t used in enough Medicare recipients to allow analysis. The cell-based vaccine the researchers did analyze contained a cell-cultured H3N2 vaccine strain component for the first time last season, though the 2009 H1N1 and influenza B vaccine viruses were produced from egg-adapted viruses.
Of the seniors who were vaccinated through the end of January, 5% got cell-cultured quadrivalent, 14% egg-based quadrivalent, and 63%, 11%, and 7% received the high-dose, adjuvanted, and standard-dose trivalent, respectively.
To gauge differences in how well all versions performed against each other, the main factor the researchers looked at was their impact against flu-related hospitalizations and emergency room visits.
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Reporting Of Adverse Events Following Influenza Vaccine
Health professionals and consumers are encouraged to report all adverse events associated with influenza vaccination in patients of any age to the TGA or through the current arrangements in their state or territory.
All reports contribute to the TGA’s ongoing monitoring of the safety of influenza vaccines.
The TGA cannot give advice about an individual’s medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a vaccine or medicine.
What Is In The Flu Shot
Every year, scientists around the world do their best to get one step ahead of the flu by developing that years iteration of the flu shot. As a reminder, vaccines work by giving your body a chance to fight off an altered version of a virus or bacteria, so that if and when it encounters the live virus in the wild, it already knows how to react, and you never get sick. But whats in a flu shot is a little more complicated.
The recipe starts with the four most common influenza strains from around the world, injected into fertilized chicken eggs or mammalian cells, deactivated so it doesnt give you the actual flu, mixed with a grab-bag of preservatives, antibiotics, and sugars. This combination is then formulated for a shot or spray to make it in time for the 2021 flu season. For those science-is-fucking-awesome types out there, this is indeed awesome.
Its also complex as hell something that keeps virologists on their toes every year. Influenza strains constantly mutate, but scientists get one shot at the annual vaccine, making their best guess some 30 weeks in advance to get the flu shot out to the public.
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Influenza Immunisation Program Advice 2022
View a summary of the Queensland government’s 2022 influenza immunisation program advice which provides important information specific to Queensland including:
- which vaccines to give for specific age groups
- information regarding people with medical conditions who are eligible for funded influenza vaccine
- vaccine ordering and supply details.
Should You Get A Flu Shot If You Have An Egg Allergy
For many years, flu shots were not recommended for people with egg allergies. The vaccine is grown in chicken eggs and it was thought that this could cause a serious allergic reaction in people with egg allergies. For this reason, flu shots were avoided by people with egg allergies. However, current research and data show that the risk of this type of reaction, even in people with significant egg allergies, is extremely low.
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What If I Think Ill Have A Reaction
If you are concerned about the possibility of a reaction, talk to your healthcare provider or pharmacist to ensure the person giving the vaccine knows what to watch for and what to do if a reaction occurs.
Because a majority of life-threatening allergic reactions occur soon after vaccination, there is no need to wait 30 minutes for observation after receiving a flu shot. However, if you get a vaccine and start to experience the symptoms of a severe allergic reaction, seek medical attention immediately. Use your Epi-Pen if you have one and call 911 or get to the Emergency Room.
How The Incredible Edible Egg May Actually Be Hampering Your Flu Vaccine
People grumble a lot about the shortcomings of the flu vaccine, which some years offers less protection than expected. What they may not know is that the source of at least some of the problems is a common item found in all grocery stores and many fridges.
The overwhelming majority of flu vaccines are made from viruses grown in eggs. This production process is inexpensive and time-tested flu vaccines have been made this way as long as flu vaccines have been made.
But the process is not ideal and it leads to issues that can undermine the vaccines effectiveness. Increasingly, experts are questioning whether the pros of egg production are worth putting up with the cons.
We need to do a lot to improve existing vaccines. And getting away from eggs would be very valuable, said Dr. Kanta Subbarao, director of the World Health Organizations influenza collaborating center in Australia.
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Why The Egg Method Won’t Work For A Coronavirus Vaccine
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Influenza Virus Surveillance For Vaccine Preparation
The large number of influenza A subtypes and the two influenza B lineages, combined with the dynamic nature of influenza through acquisition of mutations, requires constant surveillance and analysis. The World Health Organization established a network of influenza surveillance laboratories in 1952, which is now known as the Global Influenza Surveillance and Response System that currently encompasses some 143 National Influenza Centres in 113 countries and 6 WHO Collaborating Centres . This network plays a key role in the surveillance of influenza viruses and the isolation of strains in both eggs and cells, as well as providing gene sequences of these viruses . Antigenic and genetic analyses are also performed by the WHO CCs to determine whether new appearing viruses are antigenically different to the current vaccine strain. This assessment is then declared at the two influenza vaccine strain recommendation meetings held in February and September for the Northern Hemisphere and Southern Hemisphere vaccines respectively. Following this declaration of strains, either the sequences are utilised to develop recombinant vaccines or inserted into vectors to allow for reverse engineered rescue of the strain or the wildtype viruses are reassorted with high growth parental viruses. In either case, this process allows for the manufacture of current seasonal and pandemic strains.
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Do Children Adults Pregnant Women And The Elderly Need A Different Vaccine
Generally, children, adults and pregnant women get the same vaccine to protect them against the flu. However, if your child is under 9 years old and has not been vaccinated before, they will need to get 2 doses of the vaccine, at least 4 weeks apart, in their first year.
In 2018, 2 new flu vaccines became available for people aged 65 years and over. These vaccines are not available for people younger than 65.
Findings Raise New Possibilities
In an accompanying editorial, two epidemiologists from the Centers for Disease Control and Prevention’s Influenza Division wrote that understanding why seasonal flu vaccines are less effective against H3N2 and findings new ways to improve protection are critical, especially in H3N2-dominant seasons such as 2017-18. The authors are Brendan Flannery, PhD, MPH, and Alicia Fry, MD.
They said the relative effectiveness difference between the cell-culture and high-dose vaccine wasn’t statistically significant and that better effectiveness of the cell-culture vaccine was likely due to the H3N2 cell-derived component. The small relative increase suggests that egg-adaptation changes don’t entirely explain the lower vaccine effectiveness for H3N2 viruses, they add.
“One wonders how a vaccine with higher dose and absence of egg-adaptation changes would have compared in this study,” Flannery and Fry wrote
They also noted that the cell-culture and high-dose vaccines had 5% to 7% higher relative effectiveness than the adjuvanted egg-based vaccine, which was 4% more effective than standard egg-based vaccines.
“This suggests that adjuvant worked less well than increased antigen dose at improving effectiveness against A viruses,” they wrote, adding that it would be useful to know if adjuvanted vaccines offer benefits against antigenically drifted viruses, plus 2009 H1N1 and B viruses, as well as what role an adjuvanted cell-culture vaccine might play.
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