Adjupanrix (H5N1 Pandemic Influenza Vaccine)

What Is Adjupanrix and What Is It Used For?

Adjupanrix is a pre-pandemic (mock-up) influenza vaccine developed by GlaxoSmithKline Biologicals. It contains inactivated split virion H5N1 influenza virus combined with the AS03 adjuvant system. The vaccine is designed for prophylaxis of influenza during officially declared pandemic situations and is authorised for adults aged 18 years and older.

Adjupanrix represents a critical component of global pandemic influenza preparedness. Unlike seasonal influenza vaccines that are updated annually to match circulating strains, Adjupanrix was developed as a "mock-up" vaccine using the H5N1 avian influenza strain A/VietNam/1194/2004 NIBRG-14. This particular strain was selected because very few people have pre-existing immunity to it, allowing regulatory authorities to assess how well the vaccine stimulates an immune response in a largely naive population.

The concept behind a mock-up vaccine is strategically important for pandemic preparedness. By completing the full regulatory approval process with a model strain, the manufacturer can rapidly switch to the actual pandemic virus strain when a pandemic is declared, without needing to repeat the entire approval process from scratch. This significantly accelerates the availability of vaccines during a genuine pandemic emergency, potentially saving millions of lives.

The vaccine contains 3.75 micrograms of haemagglutinin antigen per 0.5 mL dose, which is considerably lower than the typical 15 micrograms found in standard seasonal influenza vaccines. This dose reduction is made possible by the inclusion of the AS03 adjuvant system, a squalene-based oil-in-water emulsion that substantially enhances the body's immune response to the antigen. The ability to use less antigen per dose is a major advantage during a pandemic, as it allows manufacturers to produce significantly more vaccine doses from the same amount of raw material.

The European Medicines Agency (EMA) granted marketing authorisation for Adjupanrix on 19 October 2009 under exceptional circumstances. This regulatory pathway was appropriate because comprehensive efficacy data cannot be collected under normal non-pandemic conditions. The authorisation is subject to annual benefit-risk reviews by the EMA, and as of the most recent assessment, the vaccine remains authorised and available for deployment when needed.

What Should You Know Before Taking Adjupanrix?

Before receiving Adjupanrix, inform your healthcare provider about any allergies (especially to eggs), current illnesses, pregnancy or breastfeeding status, and any medications you are taking. The vaccine contains trace amounts of egg protein, formaldehyde, and gentamicin, which may cause allergic reactions in sensitised individuals.

Contraindications

Adjupanrix should not be administered to individuals who have experienced a previous anaphylactic (life-threatening) allergic reaction to any component of the vaccine or its trace residues. These include egg or chicken protein (ovalbumin), formaldehyde, gentamicin sulphate, and sodium deoxycholate. A history of severe allergic reaction following a previous dose of any influenza vaccine is also a contraindication.

However, it is important to note that during an active pandemic, the risk-benefit calculation may change significantly. In such circumstances, the vaccine may be administered even to individuals with known hypersensitivity, provided that appropriate resuscitation facilities and trained medical personnel are immediately available. This reflects the potentially life-saving importance of vaccination during a severe pandemic.

Vaccination should be deferred in patients experiencing severe febrile illness (high fever). A minor infection without significant fever, such as a mild cold, is generally not a reason to postpone vaccination.

Warnings and Precautions

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following administration. Adjupanrix should be administered with caution to individuals with thrombocytopenia (low platelet count) or any bleeding disorder, as intramuscular injection may cause bleeding at the injection site in these patients.

Patients with endogenous or iatrogenic immunosuppression may have an inadequate antibody response to vaccination. This includes individuals receiving systemic corticosteroids, cytotoxic chemotherapy, radiotherapy, or other immunosuppressive treatments. While vaccination may still be recommended for these patients during a pandemic, they should be counselled that the level of protection achieved may be lower than in immunocompetent individuals.

The vaccine contains thiomersal as a preservative. Thiomersal is a mercury-containing compound present at 5 micrograms per dose (equivalent to 2.5 micrograms of organic mercury). While extensive research has found no evidence of harm from thiomersal at these concentrations, patients with known thiomersal sensitivity should be informed of its presence.

Vaccination with Adjupanrix may temporarily cause false-positive results in serological tests for HIV-1, hepatitis C virus (HCV), and human T-lymphotropic virus type 1 (HTLV-1) when tested using the ELISA method. Western blot confirmatory testing is not affected. Healthcare providers should be aware of this potential interference when interpreting laboratory results shortly after vaccination.

Pregnancy and Breastfeeding

Limited data are available regarding the use of Adjupanrix in pregnant women. Animal studies have not indicated any direct harmful effects on fertility, pregnancy, embryonic/foetal development, parturition, or postnatal development. However, as with all vaccines, the decision to vaccinate during pregnancy should be made on a case-by-case basis, weighing the potential benefits against the potential risks, particularly in the context of a declared pandemic when the risk of infection may be high.

It is not known whether Adjupanrix is excreted in human breast milk. During a pandemic situation, the benefits of vaccination for breastfeeding mothers are generally considered to outweigh any theoretical risks. Healthcare providers should discuss the specific circumstances with each patient.

How Does Adjupanrix Interact with Other Drugs?

Adjupanrix has limited data on drug interactions. Immunosuppressive agents may reduce the vaccine's effectiveness. If co-administration with another vaccine is necessary, injections should be given at different anatomical sites.

The interaction profile of Adjupanrix is relatively straightforward, as it is a vaccine rather than a systemically acting pharmaceutical agent. However, there are several important considerations that healthcare providers should be aware of when administering this vaccine.

The most clinically significant interaction involves immunosuppressive therapies. Corticosteroids (particularly at high systemic doses), cytotoxic drugs, and radiotherapy may all diminish the immune response to Adjupanrix, potentially resulting in suboptimal protection. For patients on such therapies, the timing of vaccination relative to treatment cycles should be carefully considered where possible, although during a pandemic emergency, vaccination should generally not be delayed.

No formal clinical studies have been conducted on the co-administration of Adjupanrix with other vaccines. If it is deemed necessary to administer another vaccine at the same time, the two injections should be given at different anatomical sites (for example, one in each arm). Patients and healthcare providers should be aware that adverse reactions from each vaccine may be intensified when given simultaneously.

What Is the Correct Dosage of Adjupanrix?

The standard adult dose of Adjupanrix is two injections of 0.5 mL each, administered intramuscularly at least 3 weeks apart. The vaccine is supplied as two separate components that must be mixed before administration by a qualified healthcare professional.

Adjupanrix must always be prepared and administered by trained healthcare professionals. The vaccine is supplied as a multidose presentation consisting of two separate vials: one containing the antigen suspension (split influenza virus) and one containing the AS03 adjuvant emulsion. These two components must be mixed immediately before use. Each reconstituted multidose vial yields ten doses of 0.5 mL each.

Adults (18-60 years)

Clinical trials have demonstrated that more than 80% of adults developed protective antibody levels (as measured by haemagglutination inhibition assay) after receiving the complete two-dose regimen. The immune response was robust and durable, with protective antibody titres persisting for at least six months after the second dose in the majority of subjects.

Elderly (over 60 years)

The immune response in elderly individuals may be somewhat weaker than in younger adults, which is consistent with the well-known age-related decline in immune function (immunosenescence). The AS03 adjuvant is particularly valuable in this age group, as it helps to overcome the reduced immunogenicity that older patients typically experience with non-adjuvanted vaccines.

Children

It is important to note that the EU marketing authorisation for Adjupanrix is primarily for adults aged 18 years and older. Paediatric dosing information is based on limited clinical study data. In clinical trials, children aged 3-9 years who received half-doses (0.25 mL) achieved comparable antibody levels to adults receiving full doses, likely due to their more vigorous immune systems.

Missed Dose

If the second dose of Adjupanrix is delayed beyond the recommended 3-week interval, it should be administered as soon as practically possible. There is no need to restart the vaccination series. The extended interval between doses is unlikely to significantly affect the final immune response, although prompt completion of the two-dose regimen is recommended for optimal protection, particularly during an active pandemic.

Overdose

No cases of overdose with Adjupanrix have been reported in clinical trials or post-marketing experience. If an overdose were to occur (for example, inadvertent administration of a double dose), the patient should be observed for any adverse effects. The most likely consequence would be an intensification of the expected local and systemic adverse reactions, such as increased injection site pain, more pronounced fever, or more severe myalgia. Symptomatic treatment should be provided as needed.

What Are the Side Effects of Adjupanrix?

The most common side effects of Adjupanrix include injection site reactions (pain, redness, swelling), headache, fatigue, muscle aches, joint pain, and fever. These reactions are generally mild to moderate and resolve within a few days. Serious side effects such as anaphylaxis or Guillain-Barré Syndrome are very rare.

Like all vaccines, Adjupanrix can cause side effects, although not everybody gets them. The majority of adverse reactions observed in clinical trials were mild to moderate in severity and resolved spontaneously within one to three days after vaccination. Side effects tend to be more pronounced after the first dose compared to the second dose, and younger adults may experience reactions more frequently than older individuals.

The AS03 adjuvant contributes to a somewhat higher rate of local and systemic reactions compared to non-adjuvanted influenza vaccines. This is an expected consequence of the enhanced immune stimulation provided by the adjuvant system and is generally considered an acceptable trade-off for the improved immunogenicity and antigen-sparing benefits that the adjuvant provides.

In clinical trials, cases of Bell's palsy (temporary facial paralysis) were reported, although all cases resolved spontaneously without lasting effects. Additionally, temporary false-positive serological test results for HIV, hepatitis C, and HTLV-1 have been observed following vaccination when tested using ELISA methodology. Western blot confirmatory tests are not affected.

How Should You Store Adjupanrix?

Adjupanrix must be stored in a refrigerator at 2-8°C. The vaccine must not be frozen and should be protected from light by keeping it in the original packaging. After mixing the two components, the vaccine must be used within 24 hours.

Proper storage of Adjupanrix is critical to maintaining the vaccine's potency and safety. The cold chain must be maintained throughout the entire distribution and storage process. Both the antigen suspension and the adjuvant emulsion should be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Freezing is strictly prohibited, as it can destroy the integrity of the emulsion and alter the physical properties of the adjuvant system, potentially rendering the vaccine ineffective or unsafe.

The vaccine should be stored in its original outer packaging to protect it from light. Exposure to light over time can degrade the biological components of the vaccine. Before use, both vials should be inspected visually. The antigen suspension should appear as a clear, colourless liquid, while the adjuvant emulsion should be a whitish, homogeneous, opalescent liquid. If either component shows signs of discolouration, particulate matter, or other abnormalities, it should not be used.

Once the antigen suspension and adjuvant emulsion have been mixed, the reconstituted vaccine must be used within 24 hours. During this 24-hour window, the mixed vaccine may be stored either at room temperature (up to 25°C) or returned to the refrigerator (2-8°C). Any unused vaccine remaining after 24 hours must be discarded according to local regulations for the disposal of biological waste.

What Does Adjupanrix Contain?

Each dose of Adjupanrix contains 3.75 micrograms of H5N1 haemagglutinin antigen combined with the AS03 adjuvant system (squalene, DL-alpha-tocopherol, and polysorbate 80). The vaccine also contains thiomersal as a preservative.

Active Ingredients

The active substance in Adjupanrix is split influenza virus, inactivated, from the strain A/VietNam/1194/2004 NIBRG-14 (H5N1). Each 0.5 mL dose contains 3.75 micrograms of haemagglutinin, the primary surface glycoprotein of the influenza virus against which protective antibodies are directed. The virus is propagated in embryonated hen's eggs, then chemically inactivated and split into its component parts.

AS03 Adjuvant System

The AS03 adjuvant is a proprietary squalene-based oil-in-water emulsion developed by GlaxoSmithKline. Each dose contains:

• Squalene: 10.69 mg - a naturally occurring oil found in shark liver and human sebum that serves as the primary immunostimulatory component
• DL-alpha-tocopherol (vitamin E): 11.86 mg - acts as both an antioxidant and an immunomodulatory agent
• Polysorbate 80: 4.86 mg - an emulsifying agent that stabilises the oil-in-water emulsion

Preservative and Excipients

The vaccine contains thiomersal at 5 micrograms per dose (equivalent to 2.5 micrograms of organic mercury) as a preservative. This is necessary for the multidose vial presentation to prevent microbial contamination after initial puncture. Additional excipients include sodium chloride, disodium hydrogen phosphate, potassium dihydrogen phosphate, potassium chloride, magnesium chloride, and water for injections.

Trace Residues

Due to the manufacturing process, the vaccine may contain trace amounts of the following substances: egg protein (ovalbumin) from the egg-based production system, formaldehyde used for virus inactivation, gentamicin sulphate used as an antibiotic during manufacture, and sodium deoxycholate used as a detergent in the splitting process. While present in only minute quantities, individuals with severe allergies to any of these substances should discuss vaccination with their healthcare provider.

Frequently Asked Questions About Adjupanrix