Influenza A (H5N1) vaccine

The Influenza A (H5N1) vaccine is a prescription medication belonging to the vaccine class.

The Influenza A (H5N1) vaccine is approved for use in individuals six months and older to protect against seasonal influenza viruses and lower the risk of infection, serious illness, and complications.

It is not a part of national routine immunization programmes.

The Influenza A (H5N1) vaccine is given intramuscularly, subcutaneously and intranasally, and the choice depends on the dose form, age and health considerations. It does not function according to standard pharmaceutical pharmacokinetics. Instead of passing through the normal absorption, distribution, metabolism, or elimination processes, it stimulates the immune system to produce antibodies to protect against specific influenza A virus strains belonging to the Orthomyxoviridae RNA virus.

The common side effects of the Influenza A (H5N1) vaccine include low-grade fever, mild fatigue, and pain or redness at the injection site, usually for a short period.

The Influenza A (H5N1) vaccine is available as an emulsion for injections.

The Influenza A (H5N1) vaccine is available in the United States, Canada, United Kingdom, Australia, Japan, Germany, and India.

The Influenza A vaccine belonging to the vaccine class is a sterile injectable solution.

Due to variations in immune responses and possibly alternative protective mechanisms, a particular post-vaccination hemagglutination-inhibition (HI) antibody titer has not been proven to correlate with protection against H5N1 influenza. However, the efficacy of the influenza vaccination is frequently evaluated using HI titers.

Studies indicate that HI antibody titers of less than 1:40 may, for up to 50% of patients, offer some protection against other influenza strains. Remembering that the protective threshold might vary depending on the particular influenza strain, general health, and individual factors impacting immunity is crucial. Consequently, HI titers are valuable markers of vaccination action but may only partially predict protection against all influenza types.

The Influenza A (H5N1) vaccine is available as an emulsion for injection.

Emulsion for injection: To be administered parenterally, as applicable.

The Influenza A (H5N1) vaccine can be used as follows:

• For protection against an infection caused by the H5N1 influenza virus subtype, a viral vaccination called H5N1 adjuvanted is utilised.
• It is given yearly to protect people and communities throughout flu seasons, especially for at-risk populations, including the elderly, young children, pregnant women, and those with chronic medical conditions.

The Influenza A (H5N1) vaccine can help support the following health benefits:

• Influenza prevention: For preventing influenza infections, influenza vaccinations are very effective. Protecting specific influenza A virus strains lowers the possibility of acquiring the flu. This is critical for vulnerable groups more sensitive to the severe consequences of influenza, including young children, the elderly, and people with underlying medical issues. Vaccines help prevent hospitalisations, pneumonia, and even flu-related mortality by decreasing the prevalence of the illness.
• High-risk populations: Influenza Vaccines against the A virus protect the elderly, children, pregnant women, people with weakened immune systems, and those with long-term illnesses. These populations may benefit most from immunisation since they are more likely to experience influenza-related severe outcomes. The vaccination helps public health equality and lowers healthcare inequalities by protecting these vulnerable people.
• Reduced severity of illness: The vaccination may lower the severity of the disease even if those who have received it get the influenza virus. Milder symptoms and a shorter sickness duration are the result since it improves the immune system's ability to identify and treat the virus. Ensuring that vaccinated people recover more quickly and with fewer complications reduces the burden on healthcare systems during flu seasons. Vaccination helps reduce the number of flu cases, lowering the demand for medical care, hospitalizations, and the strain on healthcare resources.
• Herd immunity: Public health benefits significantly from this widespread vaccination. The possibility of influenza A virus infection is reduced within the community. It protects the person vaccinated and individuals with weaker immune systems or those who may be unable to receive the vaccine themselves, such as infants under six months, reducing the burden on healthcare systems and improving overall community well-being.

The Influenza A (H5N1) vaccine is approved for its use in the following clinical indications:

• Prophylaxis of Influenza A in persons aged six months and above
• Prophylaxis of Influenza B in persons aged six months and above
• Children and adults with chronic lung illness, including asthma, cardiovascular disease, kidney disease, hepatitis, diabetes mellitus, neurologic disease, or isolated hypertension.
• Individuals who suffer from immunosuppression (due to drugs or HIV infection).
• Pregnancy
• Administering aspirin or drugs containing salicylates to kids and teenagers (6 months to 18 years old) increases their chance of getting Reye syndrome after acquiring the flu.
• Long-term facility occupants and inhabitants of nursing homes.
• Individuals who are obese (adult BMI more than 40)

Parenterally: The Influenza A (H5N1) vaccine is given parenterally. For children less than six months, it is not established, the vaccine is injected intramuscularly into the anterolateral thigh for children 6 to 11 months; do not inject the gluteal region or areas where a significant nerve trunk might be present and for children over 12 months of age it is injected directly into the upper arm muscle (deltoid).

When given concurrently with injectable vaccines, the shots have to be delivered using different syringes at different places. Following immunization, monitoring for at least 15 minutes for signs of acute allergic reactions is essential.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Emulsion for injection:

3.75mcg/mL or 3.75mcg/0.5mL hemagglutinin (HA) of the H5N1 influenza virus strain (AS03 adjuvant)

H5N1 influenza virus strain at a concentration of 7.5mcg/0.5mL HA (MF59 adjuvant /Audenz)

Dosage Adjustment for Adult Patients

Immunisation against H5N1 Influenza (Avian Flu)

Two dose series: 0.5 mL intramuscularly administered at intervals of 21 days.

The Influenza A (H5N1) vaccine is available as an emulsion for injection.

Influenza A (H5N1) vaccine should be used to prevent influenza A virus infections in high-risk individuals, along with no appropriate nutritional restrictions.

Influenza A (H5N1) vaccine usually has little effect on dietary or food substances when administered. Consuming regular foods and drinks before and after receiving the vaccine is safe.

Staying well hydrated by drinking water or other fluids is commonly advised. Maintaining a rich-balanced diet that includes a variety of fruits, vegetables and lean proteins can help boost the body's immunological response to the vaccine and overall health during vaccination.

The dietary restriction should be individualized as per patient requirements.

Influenza A (H5N1) vaccine may be contraindicated in the following conditions-

• Hypersensitivity (previous dose of the flu vaccine or any of its components)
• Guillain-Barré syndrome
• Severe immunosuppressive diseases like HIV/AIDS or those receiving immunosuppressive medications
• Allergic to latex rubber (present in vial stopper)

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

• Children with weak immune systems, such as those with HIV/AIDS infection or cancer or who are taking certain drugs, may not respond as well to the Influenza A (H5N1) vaccine and may consult a healthcare professional who might suggest modifying the vaccine schedule or giving additional doses to these people to improve protection.
• If the individual has a moderately critical acute sickness (with or without fever of over 101.3°F or 38.5°C), administration of the vaccine should be postponed.
• If an individual is receiving other vaccines simultaneously, healthcare providers should cautiously administer the vaccine, considering all the potential interactions and the intervals between vaccinations.
• The choice of administering influenza A (H5N1) vaccination should be based precisely on possible benefits and risks if Guillain-Barré syndrome happens within six weeks of receiving a prior influenza vaccine.

There is no sufficient scientific evidence traceable regarding the use and safety of the Influenza (H5N1) vaccine for lactating populations.

There is no sufficient scientific evidence regarding the use and safety of the Influenza A (H5N1) vaccine in concurrent use with any particular food.

The adverse reactions related to the influenza A (H5N1) vaccine can be categorized as

Common: Pain, swelling, redness at the injection site, fatigue, headache and low-grade fever.

Less common: Chills and muscle/joint pain, arthralgia and loss of appetite.

Rare: Severe Allergic Reactions (Anaphylaxis), and Guillain-Barré Syndrome (GBS).

Post-marketing Reports (Audenz)

Disorders of the blood and lymphatic system: lymphadenopathy

Disorders of the immune system: angioedema and anaphylaxis are indications of hypersensitivity responses

Among the neurological conditions are Bell Palsy, including febrile convulsions, demyelination, encephalitis, Guillain-Barre Syndrome, neuritis, paraesthesia, syncope, and encephalitis.

Conditions of the skin and subcutaneous tissues: urticaria, pruritus, and an idiopathic rash

Muscle loss conditions affecting the musculoskeletal system and connective tissue

The clinically relevant drug interactions of the influenza A (H5N1) vaccine are briefly summarized here:

• Immunosuppressants- The immunological response may be suppressed by immunosuppressive treatments such as radiation, antimetabolites, alkylating agents, cytotoxic medicines, and corticosteroids (used in dosages larger than therapeutic doses).
• Other Vaccines- Multiple vaccinations, including the Influenza A (H5N1) vaccine, given at the same time may increase the risk of adverse reactions. To reduce such a risk, medical professionals frequently adhere to vaccination regimens considering the time and space of vaccines.

The common side of the Influenza virus vaccine includes the following-

• Pain, redness or swelling where the shot was given
• Fatigue
• Headache
• Chills
• Feeling tired or weak.
• Joint pain
• GI disturbances like nausea, stomach discomfort, vomiting or diarrhoea.
• Fever.
• Loss of appetite
• Irritability
• Sleepiness

The Influenza A (H5N1) vaccine should be prudent in the following population groups.

• Pregnancy: There is no sufficient scientific evidence traceable regarding the use and safety of the Influenza (H5N1) vaccine for pregnant populations. Before using this vaccine during pregnancy, weigh the potential benefits against the possible adverse effects.

• Paediatrics: Influenza A vaccination can be beneficial and safe for children. It protects children and vulnerable populations from the flu, lowering the severity and consequences of the viral infection. During flu season, it is essential to protect the general public's health and the well-being of children.

Dosage Adjustment for Paediatric Patients

Immunisation against Influenza (H5N1) vaccine (Avian Flu)

Less than six months: Safety and effectiveness are not yet established

Six months to 17 years:

AS03 adjuvant

0.25 mL IM in a 2-dose series administered within a 21-day interval

MF59 adjuvant (Audenz)

0.5 mL IM in a 2-dose series administered within a 21-day interval

• Geriatrics: There is no sufficient scientific evidence traceable regarding the use and safety of the Influenza (H5N1) vaccine for geriatric populations.

• Lactating mothers: There is no sufficient scientific evidence traceable regarding the use and safety of the Influenza (H5N1) vaccine for lactating populations. Before using this vaccine during breastfeeding, weigh the potential benefits against the possible adverse effects.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Overdosage of the Influenza A (H5N1) vaccine rarely occurs because these vaccines are administered as pre-determined single doses based on recommended schedules by healthcare professionals according to specific or precise dosing guidelines.

There is no specific antidote or treatment for excessive Influenza A (H5N1) vaccine intake. Medical attention should be sought immediately when an overdose is suspected, followed by close monitoring for any adverse effects or allergic reactions. Supportive therapy may include, if necessary, addressing any symptoms that persist or worsen. Physical treatment might be added if required.

Pharmacodynamics of Influenza A (H5N1) vaccine:

The Influenza A (H5N1) vaccine has a potential physiological mechanism that plays a role in its pharmacodynamics, involving its interaction with the immune system. The vaccine contains inactivated influenza A viral components. After infection, immune-related cells trigger an immunological response after detecting these components as foreign matter. T cells support the formation of immunological memory, while B cells contribute to producing virus-specific antibodies. When the body is exposed to the live influenza A virus again, the immune system rapidly recognises it and destroys it to stop disease. This adaptive immune response offers protection against further viral exposure. The viability of the vaccination strains with the influenza A virus variants present in circulation determines the vaccine's effectiveness.

Pharmacokinetics of Influenza A (H5N1) vaccine:

The Influenza A (H5N1) vaccine is given subcutaneously. It does not function according to standard pharmaceutical pharmacokinetics. Instead of passing through the normal absorption, distribution, metabolism, or elimination processes, it stimulates the immune system to produce antibodies to protect against specific influenza A virus strains belonging to the Orthomyxoviridae RNA virus family, reducing the risk of infection, severe illness, and complications.

• MacDonald, Noni E et al. “The benefits of Influenza A (H5N1) vaccine in pregnancy for the fetus and the infant younger than six months of age.” Paediatrics & child health vol. 19,9 (2014): e121-2.
• Lee, I.T., Nachbagauer, R., Ensz, D. et al. Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal Influenza A (H5N1) vaccine (mRNA-1010) in healthy adults: interim analysis. Nat Commun 14, 3631 (2023). https://doi.org/10.1038/s41467-023-39376-7
• Shobana Balasingam, Annelies Wilder-Smith, Randomized controlled trials for influenza drugs and vaccines: a review of controlled human infection studies,International Journal of Infectious Diseases,Volume 49,2016,Pages 18-29,ISSN 1201-9712,https://doi.org/10.1016/j.ijid.2016.05.013.

• Explain to the caregivers the vaccine's dosage and schedule, including the benefits that vaccination reduces the risk of flu-related illness, hospitalization, and complications.
• Remind the vaccine recipient, their parents, or their guardians whether they experienced any adverse reactions from a previous dose of the Influenza A (H5N1) vaccine. Also, inform them that the shot should be given annually before or during flu season.
• Assure caregivers that Influenza A (H5N1) vaccine immunizations are generally safe, with only minor, short side effects. Encouraging them to immediately report any unexpected or severe responses to the healthcare physician and, whenever applicable, to use reporting systems like the Vaccine Adverse Event Reporting System (VAERS)
• Inform caregivers of the recommended immunization schedule, which usually consists of two or three doses, depending on the vaccine brand. Also, mention the ages at which the doses should be administered and give the Vaccine Information Statements, which must be disclosed before immunization by the National Childhood Vaccine Injury Act of 1986 about the Centres for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines), these resources are freely accessible.

https://main.mohfw.gov.in/sites/default/files/Universal.pdf

https://www.indianpediatrics.net/oct2014/785 figure1.pdf

https://www.ncbi.nlm.nih.gov/books/NBK537197/

http://www.cdc.gov/vaccines/schedules/hcp/index.html