Tuesday, March 21, 2023

Flu Vaccine Mechanism Of Action

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Influenza A Vaccine Description

SwineFlu Influenza H1N1 Mechanism of Action MOA Animation

Influenza A 2009 Monovalent Vaccine, for intramuscular injection, is a sterile, clear, colorless to slightly opalescent suspension with some sediment that resuspends upon shaking to form a homogeneous suspension. Influenza A 2009 Monovalent Vaccine is prepared from influenza virus propagated in the allantoic fluid of embryonated chicken eggs. Following harvest, the virus is purified in a sucrose density gradient using a continuous flow zonal centrifuge. The purified virus is inactivated with beta-propiolactone, and the virus particles are disrupted using sodium taurodeoxycholate to produce a “split virion”. The disrupted virus is further purified and suspended in a phosphate buffered isotonic solution.

Influenza A 2009 Monovalent Vaccine is formulated to contain 15 mcg hemagglutinin per 0.5 mL dose of influenza A/California/7/2009 v-like virus.

Thimerosal, a mercury derivative, is not used in the manufacturing process for the single dose presentations therefore these products contain no preservative. The multi-dose presentation contains thimerosal, added as a preservative each 0.5 mL dose contains 24.5 mcg of mercury.

The rubber tip cap and plunger used for the preservative-free, single-dose syringes and the rubber stoppers used for the multi-dose vial contain no latex.

Assessment Of Vaccine Delivery

The difference between the antigen content measured by single radial immunodiffusion assay of unused MNPs per vaccine strain) and that of the residual antigen content of the 11 MNPs used in the substudy showed that the mean HA dose delivered by MNPs was 10.8g 1.1) for the H1N1 strain, 14.4g for the H3N2 strain, and 13.3g for the B strain27. Our measurements also showed that the IM injection administered 18g of HA per H1N1 vaccine strain, 17g of HA per H3N2 vaccine strain, and 15g of HA per B vaccine strain with a delivery efficiency of 60%, 85%, and 89%, respectively. Mean dose delivered by each strain significantly differed between MNP and IM groups .

Other Adverse Reactions Associated With Influenza Vaccination

Anaphylaxis has been reported after administration of AFLURIA. Although AFLURIA and Influenza A 2009 Monovalent Vaccine contain only a limited quantity of egg proteins, these proteins can induce immediate hypersensitivity reactions among persons who have severe egg allergy. Allergic reactions include hives, angioedema, asthma, and systemic anaphylaxis .

The 1976 swine influenza vaccine was associated with an increased frequency of GBS. Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. If influenza vaccine does pose a risk, it is probably slightly more than one additional case per 1 million persons vaccinated.

Neurological disorders temporally associated with influenza vaccination, such as encephalopathy, optic neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy, have been reported.

Microscopic polyangiitis has been reported temporally associated with influenza vaccination.

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Why Do We Need The Flu Vaccine Every Year

Flu vaccines have an excellent safety record. They are the best protection we have against an unpredictable virus which can cause severe illness and deaths each year among at-risk groups. It is important to have a flu vaccine every year because the flu virus is very variable and changes over time. Each year there are different strains around, and a new vaccine has to be prepared to deal with them. Vaccination from previous years is not likely to protect people against current strains of flu.

Each years flu vaccine is made to give the best protection against the strains of flu that are expected to circulate in the coming season. The trivalent vaccine protects against three of the flu virus strains which are most likely to be around. The quadrivalent vaccine protects against four flu virus strains. However, decisions about what to put in the flu vaccine have to be made six months before the flu season starts.

Every February in the Northern Hemisphere, the World Health Organization reviews the types of flu that have been circulating in all parts of the world and chooses the ones which will go into the vaccine for the following autumn. This allows time for the vaccine to be made but it also gives the flu virus time to change before vaccination starts in the autumn. This means that sometimes the flu vaccine may not be a good match for all the strains of flu that are circulating. Read more about the WHO recommendations for the 2022-23 season.

Precautions While Using Influenza Virus Vaccine

The human antibody response to influenza A virus infection and ...

It is very important that your child return to your doctors office at the right time if your child needs a second dose of the vaccine. Be sure to notify your doctor of any side effects that occur after you or your child receive this vaccine.

This vaccine may cause a serious allergic reaction called anaphylaxis, which can be life-threatening and requires immediate medical attention. Tell your doctor right away if you or your child have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after receiving the injection.

Children who have received a certain brand of the influenza vaccine have developed a fever and in some cases a fever with seizures. Talk with your doctor if you have concerns about this.

If you are very sick and have a high fever, you will probably need to wait until you are well before you receive this vaccine.

Influenza virus vaccine may not protect everyone who receives it. It will not also treat flu symptoms if you already have the virus.

The tip cap of the prefilled syringe for certain brands of the injection contains dry natural rubber , which may cause allergic reactions in people who are sensitive to latex. Tell your doctor if you or your child have a latex allergy before you receive this vaccine.

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Same Target Different Approach

While the discussion above has focused on improving the influenza vaccine pipelines currently in use, such approaches are still limited by factors intrinsic to the TIV and LAIV platforms themselves. As such, it is likely that major improvements to influenza vaccines will come about through development of distinct vaccination platforms. Correspondingly, new vaccine delivery and manufacturing technologies are being investigated for use in production of influenza vaccines. These vaccine approaches include the use of vectored or expressed HA antigens and/or targeting of different viral antigens.

Vaccine Supply And Distribution

How much influenza vaccine is projected to be available for the 2021-2022 influenza season?

Flu vaccine is produced by private manufacturers, so supply depends on manufacturers. Vaccine manufacturers have projected that they will supply the United States with as many as 188 million to 200 million doses of influenza vaccine for the 2021-2022 season. These projections may change as the season progresses. All flu vaccines for the 2021-2022 season will be quadrivalent . Most will be thimerosal-free or thimerosal-reduced vaccine and about 18% of flu vaccines will be egg-free.

Where can I find information about vaccine supply?

Special Consideration Regarding Egg Allergy

People with egg allergies can receive any licensed, recommended age-appropriate influenza vaccine that is otherwise appropriate. People who have a history of severe egg allergy should be vaccinated in a medical setting, supervised by a health care provider who is able to recognize and manage severe allergic reactions. Two completely egg-free flu vaccine options are available: quadrivalent recombinant vaccine and quadrivalent cell-based vaccine.

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Advances In Development And Application Of Influenza Vaccines

  • 1School of Life Science and Engineering, Foshan University, Foshan, China
  • 2Department of Veterinary & Biomedical Sciences, University of Minnesota, Twin Cities, MN, United States

Influenza A virus is one of the most important zoonotic pathogens that can cause severe symptoms and has the potential to cause high number of deaths and great economic loss. Vaccination is still the best option to prevent influenza virus infection. Different types of influenza vaccines, including live attenuated virus vaccines, inactivated whole virus vaccines, virosome vaccines, split-virion vaccines and subunit vaccines have been developed. However, they have several limitations, such as the relatively high manufacturing cost and long production time, moderate efficacy of some of the vaccines in certain populations, and lack of cross-reactivity. These are some of the problems that need to be solved. Here, we summarized recent advances in the development and application of different types of influenza vaccines, including the recent development of viral vectored influenza vaccines. We also described the construction of other vaccines that are based on recombinant influenza viruses as viral vectors. Information provided in this review article might lead to the development of safe and highly effective novel influenza vaccines.

Immunogenicity In A Pediatric Population

Vaccines and the Immune Response: How Vaccines Work

An open-label, uncontrolled, multi-center study to evaluate the safety, tolerability and immunogenicity of AFLURIA in children 6 months to 9 years of age was conducted in Australia. The study subjects were subdivided into two groups dependent upon age at time of enrollment. A total of 298 subjects were enrolled, including 151 subjects, 6 months to less than 3 years and 147 subjects, 3 years to less than 9 years .

Two doses of AFLURIA were administered to all subjects, with a 30 day interval between each dose. Children ages 6 months to less than 3 years received two 0.25 mL doses of AFLURIA. Children ages 3 years to less than 9 years were administered two 0.5 mL doses of AFLURIA. Sera for immunological assessment were taken 30 days following each vaccination. Immunogenicity endpoints were the seroconversion rate and the proportion of subjects with a minimum post-vaccination HI antibody titer of 1:40. The results for each dose are presented in Table 7.

For both age groups, the vaccine met FDA acceptance criteria for immunogenicity developed for healthy adults for all three influenza strains following two doses. These criteria are: 1) that the lower bound of the 2-sided 95% CI for the seroconversion rate should be at least 40% and 2) the lower bound of the 2-sided 95% CI for the proportion of subjects with a post-vaccination HI titer of 1:40 should be at least 70%.

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Types Of Seasonal Influenza Vaccine

Two types of influenza vaccine are widely available: inactivated influenza vaccines and live attenuated influenza vaccines . Traditionally, influenza vaccines have been produced to protect against 3 different seasonal influenza viruses . In most countries this is still the case and the current trivalent vaccines contain influenza A, pandemic A and 1 of 2 influenza B lineage viruses. However, recently vaccines which protect against 4 different viruses, including both influenza B lineage viruses , have become available in some countries.

Regardless of the type or composition of seasonal influenza vaccine, vaccination should be administered annually to provide optimal protection against infection.

Box 1 Types Of Influenza

There are four types of influenza virus: types A, B, C, and D. Influenza A and B viruses cause seasonal epidemics in humans. While influenza A virus circulates in humans and a variety of animals in addition, such as birds, pigs, dogs, and horses, influenza B virus infection is limited to humans and seals. Influenza C virus causes a mild respiratory illness only in humans. Influenza D virus has not been shown to cause illness in humans.

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Route Of Vaccine Delivery

Another approach being explored to increase the immunogenicity of influenza vaccines is to differentially stimulate the immune system through alternative delivery routes. Such an approach in terms of influenza vaccine delivery is intradermal inoculation, with the rationale of engaging the abundant pool of professional antigen-presenting cells in the skin. APCs are efficient at capturing and processing antigens for subsequent presentation in the lymphoid organs, resulting in stimulation of both innate and adaptive immunity . In some cases, i.d. vaccines performed better than the conventional intramuscular or subcutaneous vaccines in stimulating a robust immune response . This approach is especially relevant for the elderly, since in two head-to-head studies, i.d. vaccines were superior to i.m. vaccines in terms of immunogenicity in the elderly . Initial reports on the i.d. delivery of the influenza vaccine in healthy adults showed that it was as efficacious as i.m. vaccines in stimulating an antibody response, even with only half the standard dose of HA . A systematic review of clinical studies with i.d. vaccines showed that most studies reported comparable immunogenicity between reduced doses of i.d. vaccines and standard i.m. vaccines , suggesting that i.d. vaccination could provide a dose-sparing strategy.

Who Should Get The Flu Vaccine

Investigation,managemnt and vaccination of influenza (2)

Everyone over 6 months of age should get the flu vaccine yearly. If the free vaccination program doesn’t cover you, you can still get the vaccine at a fair cost.

Many employers offer free vaccination to staff, and some pharmacists can give the flu jab, as well as GPs and clinics, local council community health clinics, schools, aged care facilities and hospitals.

You may need a flu vaccine if you work in or visit an aged or disabled care facility. You may need to show proof of flu vaccination before you enter. If you get the vaccine, you can get an immunisation history statement at the Australian Immunisation Register.

Ask your GP, clinic or pharmacist where you can get your flu vaccine.

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Safety Experience From Clinical Studies

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a vaccine cannot be directly compared to rates in the clinical studies of another vaccine and may not reflect the rates observed in clinical practice.

Clinical data for AFLURIA have been obtained in four clinical studies, three in adult populations and one in a pediatric population . Safety data are provided for two of the adult studies and the pediatric study.

A US study included 1,357 subjects for safety analysis, ages 18 to less than 65 years, randomized to receive AFLURIA or placebo . There were no deaths or serious adverse events reported in this study.

A UK study included 275 subjects, ages 65 years and older, randomized to receive preservative-free AFLURIA or a European-licensed trivalent inactivated influenza vaccine as an active control . There were no deaths or serious adverse events reported in this study.

An open-label, uncontrolled study in children, conducted in Australia , included 298 subjects, ages 6 months to less than 9 years. All subjects received preservative-free AFLURIA administered as two doses, one month apart . Subjects were subdivided into two age groups: children ages 6 months to less than 3 years received two 0.25 mL doses of AFLURIA and children ages 3 years to less than 9 years received two 0.5 mL doses of AFLURIA. There were no deaths or vaccine-related serious adverse events reported in this study.

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Immunological Deconstruction Of Vaccines

Vaccines can be classified into two broad groups. The first group, live attenuated vaccines, comprises weakened versions of the pathogens these mimic the kind of protective immunity induced in people who survive live infection22. Examples of this group include vaccines against acute infections caused by invariant pathogens such as smallpox, yellow fever, measles, mumps, rubella and chicken pox. Live attenuated vaccines have been administered to billions of people worldwide and elicit strong cellular and antibody responses and often confer immunity that lasts for several decades, with even a single immunization22. However, in many acute infections, such as infection with respiratory syncytial virus and malaria, natural infection itself does not engender complete protection against reinfection, so any vaccine must improve on what nature has evolved. Furthermore, pathogens that mutate rapidly , those that exist as multiple serotypes or those that cause persistent or latent infection pose formidable immunological challenges22.

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What Is Being Done To Improve Influenza Vaccines

For more than a decade, collaborative efforts in the United States across the federal government and the private sector have led to improved influenza vaccine technologies that have expanded vaccine supply and/or improved vaccine effectiveness.

To further support improvement of influenza vaccines, the White House issued Executive Order 13887: Modernizing Influenza Vaccines in the United States to Promote National Security and Public Health on September 19, 2019. The EO established a National Influenza Vaccine Task Force, which CDC is a member of, and calls for the modernization of influenza vaccines and vaccine manufacturing along with increased national influenza vaccination.

Influenza Virus Vaccine Side Effects

Neuraminidase Inhibitors: Mechanism of Action

In 1976, a number of people who received the swine flu influenza vaccine developed Guillain-Barré syndrome , which is a disease that may cause paralysis. Most of these people were over 25 years of age. Although only 10 out of every one million people who received the vaccine actually developed GBS, this number was 6 times higher than would normally have been expected. Most of the people who got GBS recovered completely.

It is assumed that the swine flu virus included in the 1976 vaccine caused the problem, but this has not been proven. Since that time, studies have shown that the risk of acquiring GBS from an influenza vaccine is very low .

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common

  • Bruising, hard lump, redness, or pain at the injection site
  • cough
  • large, flat, blue or purplish patches in the skin
  • loss of appetite
  • swelling or puffiness of the face
  • unusual tiredness or weakness
  • fast heartbeat
  • hives, itching, or skin rash
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • noisy breathing

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Generation Of Broadly Protective Vaccines

Current inactivated vaccines provide some protection to vaccine recipients from viruses that are antigenically similar to the vaccine viruses. However, such vaccines fail to suppress infections caused by antigenically drifted viruses and offer no protection against an antigenic shifted virus that has the potential to cause a pandemic. Therefore, there is a need for a vaccine capable of inducing immune responses that last for a long time and that protect against a wide range of viruses, ideally all influenza A and B viruses. Several approaches have been taken to produce such vaccines based on the concept of inducing immune responses against the conserved protective epitopes in virus proteins. The targets of universal vaccine candidates include the HA stem, the RBS of HA, the extracellular domain of M2 , and the CTL epitopes in M1 and NP.

Despite the high variability of the HA head, the RBS is functionally conserved because sialic acid receptor recognition is an essential step for influenza virus entry. Antibodies against the RBS mimic the binding mode of sialic acid to some extent, resulting in a high cross-neutralizing capability,,. Although the RBS could be a target for a broadly protective vaccine, such a vaccine is not being actively investigated because of the lack of an optimally designed antigen. However, efforts towards this goal are underway, as are efforts towards the development of antiviral drugs targeting the RBS,.

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