Foclivia: Uses, Dosage & Side Effects
An MF59-adjuvanted pandemic influenza vaccine (H5N1) for active immunization against avian influenza in a declared pandemic
Foclivia is an inactivated, MF59-adjuvanted pandemic influenza vaccine designed for active immunization against the H5N1 subtype of influenza A virus. Authorized by the European Medicines Agency (EMA) under exceptional circumstances as part of pandemic preparedness, Foclivia contains purified surface antigens (haemagglutinin and neuraminidase) from the A/Vietnam/1194/2004 (H5N1) influenza strain combined with the MF59C.1 adjuvant, an oil-in-water emulsion that significantly enhances the immune response. The vaccine is intended for deployment during a declared H5N1 pandemic and is administered as two intramuscular doses given at least three weeks apart. Clinical trials have demonstrated that Foclivia elicits robust seroprotective antibody responses in a high proportion of vaccinated individuals across all age groups, from infants aged 6 months to elderly adults, while maintaining an acceptable safety profile consistent with other adjuvanted influenza vaccines.
Quick Facts: Foclivia
Key Takeaways
- Foclivia is an MF59-adjuvanted, inactivated pandemic influenza vaccine authorized in the EU for protection against H5N1 avian influenza during a declared pandemic, suitable for individuals aged 6 months and older.
- The primary vaccination schedule consists of two intramuscular doses of 0.5 mL (or 0.25 mL for children under 3 years) given at least 3 weeks apart, with a booster dose recommended 12 months after the primary series if ongoing protection is needed.
- The MF59C.1 adjuvant enables the use of a lower antigen dose (7.5 µg haemagglutinin per dose) while producing robust antibody responses, which is critical for maximizing vaccine supply during a pandemic.
- Common side effects include injection site reactions (pain, redness, swelling), headache, fatigue, and myalgia, which are generally mild to moderate and resolve within 1–3 days without treatment.
- The vaccine should be stored at 2–8 °C (do not freeze), protected from light, and should only be administered by trained healthcare professionals in settings equipped to manage anaphylaxis.
What Is Foclivia and What Is It Used For?
Foclivia is a pandemic influenza vaccine developed for protection against the H5N1 subtype of influenza A virus, commonly known as avian influenza or “bird flu.” The vaccine was granted marketing authorization by the European Medicines Agency (EMA) under exceptional circumstances as a “mock-up” pandemic vaccine. This means it was developed and authorized in advance of a pandemic using an H5N1 virus strain, so that in the event of an actual H5N1 pandemic declaration by the World Health Organization (WHO), the vaccine can be rapidly deployed to protect populations.
The H5N1 influenza virus has been a persistent global health concern since the late 1990s, when it was first identified as causing severe illness and death in humans who had direct contact with infected poultry. While sustained human-to-human transmission of H5N1 has not yet been established, the virus continues to circulate widely among avian populations across multiple continents, and sporadic human infections with high case fatality rates (historically exceeding 50% in confirmed cases) continue to be reported. The WHO, the European Centre for Disease Prevention and Control (ECDC), and national health agencies worldwide maintain H5N1 as a priority pathogen for pandemic preparedness planning. The development of pre-pandemic vaccines such as Foclivia is a critical component of this preparedness strategy.
Foclivia contains purified surface antigens — specifically haemagglutinin (HA) and neuraminidase (NA) — derived from the A/Vietnam/1194/2004 (H5N1) influenza virus strain propagated in embryonated hen’s eggs. The surface antigens are the proteins on the outer surface of the influenza virus that are recognized by the human immune system and are the primary targets of protective antibody responses. Each 0.5 mL dose of Foclivia contains 7.5 micrograms of haemagglutinin, which is notably lower than the 15 micrograms of HA typically contained in standard seasonal influenza vaccines. This antigen-sparing approach is made possible by the inclusion of the MF59C.1 adjuvant.
The MF59C.1 adjuvant is a proprietary oil-in-water emulsion developed by Novartis (now Seqirus) that contains squalene as its principal component. Squalene is a naturally occurring organic compound found in the human body (particularly in the liver and skin) and in various plant and animal sources, including olive oil and shark liver oil. When formulated as a nanoemulsion in MF59, squalene acts as a powerful immunostimulant. The MF59 adjuvant works through several complementary mechanisms: it creates a local immunocompetent environment at the injection site by recruiting immune cells (monocytes, macrophages, and dendritic cells), enhances antigen uptake and presentation by antigen-presenting cells, promotes the activation and differentiation of T-helper cells and B cells in the draining lymph nodes, and stimulates the production of a broader repertoire of antibodies, including antibodies that can cross-react with drifted virus variants.
The inclusion of MF59 in Foclivia serves two critical purposes for pandemic preparedness. First, by boosting the immune response to the vaccine antigen, MF59 allows a lower dose of haemagglutinin to be used per injection (7.5 µg instead of the standard 15 µg), effectively doubling the number of vaccine doses that can be produced from a given quantity of antigen. During a pandemic, when global demand for vaccines would vastly outstrip initial supply, this antigen-sparing effect is of enormous strategic importance. Second, the adjuvant has been shown to induce broader cross-reactive immunity, meaning that antibodies generated against the vaccine strain may also provide some degree of protection against antigenically drifted H5N1 variants that could emerge during a pandemic.
Clinical trials conducted with Foclivia have demonstrated that the vaccine meets the immunogenicity criteria established by the Committee for Medicinal Products for Human Use (CHMP) of the EMA. In studies involving healthy adults aged 18–60 years, a two-dose vaccination schedule (with doses administered 3 weeks apart) resulted in seroprotection rates (defined as an haemagglutination inhibition [HI] antibody titer of ≥1:40) exceeding 70% of subjects, seroconversion rates (defined as a ≥4-fold increase in HI titer from baseline) exceeding 40%, and geometric mean titer ratios exceeding 2.5-fold increases. These immunogenicity results have also been confirmed in studies involving elderly subjects (>60 years) and pediatric populations (6 months to 17 years), although antibody responses tend to be somewhat lower in the elderly and vary by age group in children.
Foclivia is part of a broader pandemic preparedness framework. Mock-up vaccines like Foclivia are authorized in advance so that, in a pandemic, the manufacturer can rapidly update the vaccine strain if needed (a “strain change”) and begin large-scale production with minimal regulatory delay. This approach was validated during the 2009 H1N1 influenza pandemic when similar mock-up authorizations enabled rapid deployment of pandemic vaccines across Europe.
What Should You Know Before Receiving Foclivia?
Contraindications
The primary contraindication to Foclivia is a history of anaphylaxis (severe, life-threatening allergic reaction) to a previous dose of Foclivia or to any component of the vaccine. The vaccine is produced using embryonated hen’s eggs and may contain residual traces of egg proteins, including ovalbumin. Individuals with a confirmed history of severe anaphylactic reaction to egg protein should not receive Foclivia. However, it is important to distinguish between severe egg anaphylaxis and milder forms of egg allergy — individuals who can tolerate small amounts of egg in their diet may still be eligible for vaccination under medical supervision with appropriate observation.
Foclivia may also contain trace amounts of the following substances from the manufacturing process: neomycin (an antibiotic), kanamycin (an antibiotic), barium sulfate, formaldehyde, and cetyltrimethylammonium bromide (CTAB). Individuals with known severe hypersensitivity to any of these substances should not receive the vaccine. If you are unsure whether you have an allergy to any vaccine component, discuss this with your healthcare provider before vaccination.
Warnings and Precautions
As with all injectable vaccines, appropriate medical treatment and supervision must be immediately available in case of an anaphylactic reaction following administration of Foclivia. Vaccinated individuals should remain under observation for at least 15–30 minutes after injection. Healthcare professionals administering the vaccine must be trained in the recognition and treatment of anaphylaxis.
Before receiving Foclivia, inform your healthcare provider about the following:
- Febrile illness: Vaccination should be postponed in individuals with moderate or severe acute febrile illness (fever). A minor illness without fever (such as a mild upper respiratory tract infection) is generally not a reason to delay vaccination, particularly during a pandemic when timely immunization is critical.
- Bleeding disorders: If you have a bleeding disorder such as thrombocytopenia or hemophilia, or if you are taking anticoagulant medications (blood thinners), inform your doctor. Intramuscular injections can cause bleeding at the injection site in these individuals. The vaccine should be administered with caution, using a fine needle, and firm pressure should be applied to the injection site for at least 2 minutes without rubbing.
- Immunodeficiency: If your immune system is weakened (immunocompromised) due to a medical condition (such as HIV/AIDS) or immunosuppressive treatment (such as chemotherapy, high-dose corticosteroids, or biological therapies), the vaccine may not produce an adequate immune response. Vaccination may still be recommended in these individuals because the benefits generally outweigh the risks, but additional doses or closer monitoring may be needed. Discuss your specific situation with your healthcare provider.
- Guillain-Barré Syndrome (GBS): If you have a history of Guillain-Barré Syndrome (a rare condition where the immune system attacks the peripheral nerves) following a previous vaccination, inform your doctor. Although the risk of GBS following influenza vaccination is very low, a careful benefit-risk assessment should be made.
- Syncope (fainting): Fainting can occur following, or even before, vaccination, particularly in adolescents and young adults. This is a vasovagal reaction and can result in injury if the individual falls. Individuals should be seated or lying down during the injection and observed for signs of faintness for at least 15 minutes after vaccination.
Pregnancy and Breastfeeding
Limited clinical data are available on the use of Foclivia specifically during pregnancy. However, extensive safety data are available from MF59-adjuvanted seasonal influenza vaccines (such as Fluad) administered to pregnant women, and no increased risk of adverse pregnancy outcomes has been identified. Additionally, data from non-adjuvanted H5N1 vaccines given during pregnancy have not shown harmful effects.
In a pandemic situation, the WHO and most national health authorities recommend that pregnant women be prioritized for vaccination because influenza infection during pregnancy is associated with increased risks of severe illness, hospitalization, intensive care admission, and adverse pregnancy outcomes including preterm birth and fetal death. The decision to vaccinate a pregnant woman with Foclivia should be made on an individual basis, taking into account the risk of exposure to the pandemic virus and the recommendations of relevant public health authorities.
It is not known whether the vaccine antigens or antibodies induced by Foclivia are excreted in human breast milk. However, inactivated influenza vaccines are generally considered compatible with breastfeeding. Antibodies produced by the mother may provide some passive protection to the breastfed infant. The potential benefits of vaccination for breastfeeding mothers, particularly during a pandemic, are likely to outweigh any theoretical risks.
Children and Adolescents
Foclivia is authorized for use in individuals aged 6 months and older. The dosing differs by age group: children aged 6 months to under 36 months (3 years) receive a reduced dose of 0.25 mL per injection, while children aged 3 years and older receive the standard adult dose of 0.5 mL. Both age groups require two doses given at least 3 weeks apart. Clinical studies in pediatric populations have demonstrated that Foclivia is immunogenic in children, although the specific antibody titers achieved may vary depending on the age group and prior influenza exposure.
For infants under 6 months of age, there are insufficient data to recommend vaccination with Foclivia. Protection of very young infants during a pandemic is best achieved through vaccination of close contacts (a “cocooning” strategy), including parents and other household members.
Foclivia is produced in embryonated hen’s eggs and may contain residual egg protein. However, for individuals with mild egg allergy (those who can eat baked goods containing egg), vaccination may still be possible under medical supervision. Only individuals with a confirmed history of severe anaphylaxis to egg protein are absolutely contraindicated. In a pandemic, the benefits of vaccination will often outweigh the risks even in egg-allergic individuals — consult an allergist or your healthcare provider.
How Does Foclivia Interact with Other Drugs?
As an inactivated vaccine, Foclivia does not undergo systemic metabolism in the same way as conventional pharmaceutical drugs. It does not interact with cytochrome P450 enzymes or other drug metabolism pathways, and therefore traditional pharmacokinetic drug-drug interactions are not a concern. However, there are several important pharmacodynamic considerations regarding co-administration with other treatments and vaccines.
The following table summarizes the key interaction considerations for Foclivia:
| Category | Examples | Interaction Status | Recommendation |
|---|---|---|---|
| Other inactivated vaccines | Seasonal influenza, tetanus, pneumococcal | No significant interaction | May be co-administered at different injection sites |
| Live attenuated vaccines | MMR, varicella, nasal influenza spray | No interference expected | Can be given simultaneously or at any interval |
| Immunosuppressive drugs | Corticosteroids, methotrexate, biologics, chemotherapy | May reduce immune response | Vaccinate; response may be suboptimal. Additional doses may be considered. |
| Anticoagulants | Warfarin, heparin, DOACs (rivaroxaban, apixaban) | No effect on vaccine efficacy | Use fine needle; apply pressure for 2 min post-injection |
| Antipyretics/Analgesics | Paracetamol, ibuprofen | Prophylactic use may reduce immune response | Use for symptom relief after vaccination; avoid prophylactic use |
| Antibiotics | Amoxicillin, azithromycin, ciprofloxacin | No interaction | No dose adjustment needed |
Major Interactions
The most clinically significant interaction is with immunosuppressive therapies. Patients receiving systemic corticosteroids at high doses (equivalent to ≥20 mg/day of prednisolone for ≥2 weeks), cytotoxic chemotherapy, biological disease-modifying antirheumatic drugs (bDMARDs such as rituximab, which depletes B cells), or organ transplant rejection prophylaxis may have a significantly diminished antibody response to Foclivia. For patients on rituximab, vaccination should ideally be timed to occur at least 6 months after the last rituximab infusion and at least 4 weeks before the next planned infusion to maximize the chance of mounting an adequate immune response. However, during a pandemic, vaccination should not be withheld or delayed solely because of immunosuppressive treatment — even a reduced immune response may provide partial protection.
Minor Interactions
Prophylactic use of antipyretic/analgesic medications (such as paracetamol or ibuprofen) before or at the time of vaccination has been associated with a modest reduction in antibody responses to some vaccines in clinical studies. While this effect has not been specifically studied with Foclivia, it is generally recommended that antipyretics and analgesics be used for symptomatic relief of post-vaccination side effects (such as injection site pain, headache, or fever) rather than taken prophylactically before vaccination. If you develop side effects after receiving Foclivia, taking paracetamol or ibuprofen for symptom relief is appropriate and will not significantly impact your overall immune response.
There are no known interactions between Foclivia and dietary supplements, herbal products, or common over-the-counter medications other than those described above. Alcohol consumption in moderation is not expected to affect the immune response to the vaccine, although excessive alcohol intake can impair immune function generally.
If a pandemic occurs during the seasonal influenza period, Foclivia can be administered concurrently with seasonal influenza vaccines. The two vaccines should be given at different injection sites (e.g., one in each arm). Studies have shown that co-administration of adjuvanted and non-adjuvanted influenza vaccines does not result in clinically meaningful interference with the immune response to either vaccine.
What Is the Correct Dosage of Foclivia?
Foclivia is administered exclusively by intramuscular injection. It must never be given intravenously, subcutaneously, or intradermally. The preferred injection site is the deltoid muscle of the upper arm in adults and children over 1 year of age, and the anterolateral aspect of the thigh in infants and young children. The vaccine should be gently shaken before use to produce a uniform, milky white suspension. Do not use the vaccine if it contains particles or if the appearance is abnormal.
Adults (18–60 years)
Primary Vaccination
Two doses of 0.5 mL each, administered by intramuscular injection with an interval of at least 3 weeks between doses. Clinical studies have shown that optimal immunogenicity is achieved with a 3-week interval, although intervals of up to 6 weeks may be used when logistically necessary without significantly compromising the immune response.
Booster Dose
A single booster dose of 0.5 mL may be administered approximately 12 months after the first dose of the primary vaccination series. Booster vaccination has been shown to produce a strong anamnestic (memory) immune response with a rapid rise in antibody titers, including cross-reactive antibodies against drifted H5N1 virus variants. The decision to administer a booster will depend on the epidemiological situation and the recommendations of public health authorities.
Elderly (>60 years)
Primary Vaccination
The dosing schedule for elderly adults is the same as for younger adults: two doses of 0.5 mL given at least 3 weeks apart. Immunogenicity studies have shown that elderly subjects may achieve somewhat lower antibody titers compared to younger adults, which is consistent with the general age-related decline in immune function (immunosenescence). However, the MF59 adjuvant has been shown to be particularly beneficial in elderly populations, producing significantly higher antibody responses compared to non-adjuvanted vaccines. Booster doses may be particularly important in this age group.
Children and Adolescents
| Age Group | Dose per Injection | Number of Doses | Minimum Interval |
|---|---|---|---|
| 6–35 months | 0.25 mL | 2 | At least 3 weeks |
| 3–8 years | 0.5 mL | 2 | At least 3 weeks |
| 9–17 years | 0.5 mL | 2 | At least 3 weeks |
| Adults ≥18 years | 0.5 mL | 2 | At least 3 weeks |
For children aged 6–35 months, the half-dose (0.25 mL) can be obtained by drawing up the appropriate volume from a multi-dose vial presentation, or by partially expelling the contents of a pre-filled syringe to the graduation mark, if available. Healthcare professionals must be trained in the correct technique to ensure accurate dosing in this age group.
Missed Dose
If the second dose of the primary vaccination series is not given at the recommended interval, it should be administered as soon as possible. There is no need to restart the vaccination series; a delayed second dose is still expected to produce a booster response. However, the individual may not be optimally protected during the interval between the scheduled and actual administration of the second dose. During a pandemic, every effort should be made to adhere to the recommended schedule to ensure timely protection.
Overdose
Overdose with Foclivia is unlikely because the vaccine is supplied in single-dose pre-filled syringes (or dispensed in measured doses from multi-dose vials) and is administered by trained healthcare professionals. In the event that an overdose is inadvertently administered (e.g., a full 0.5 mL dose given to an infant who should have received 0.25 mL), no specific treatment is required. The individual should be monitored for any adverse reactions, and the event should be documented. Adverse reactions following an overdose are expected to be similar to those following a standard dose, possibly with increased local reactogenicity.
Foclivia must never be administered intravenously. Intravascular injection can cause severe adverse reactions. The vaccine should be administered strictly by intramuscular injection into the deltoid muscle (adults/older children) or the anterolateral thigh (infants/young children). Aspiration before injection (pulling back on the syringe plunger) is no longer routinely recommended by WHO, as intramuscular injection sites do not contain large blood vessels.
What Are the Side Effects of Foclivia?
Like all vaccines, Foclivia can cause side effects, although not everybody gets them. The side effects observed in clinical trials with Foclivia are consistent with those typically seen with adjuvanted influenza vaccines. The MF59 adjuvant tends to produce slightly more local reactogenicity (injection site reactions) compared to non-adjuvanted vaccines, but this increased local response is a reflection of the enhanced immune activation at the injection site that contributes to the superior immunogenicity of the vaccine.
The following side effects have been reported in clinical trials and post-marketing surveillance. They are classified by frequency according to the standard convention:
Very Common
Affects more than 1 in 10 people
- Pain at the injection site
- Hardening (induration) at the injection site
- Redness (erythema) at the injection site
- Swelling at the injection site
- Headache
- Fatigue
- Muscle pain (myalgia)
- General feeling of being unwell (malaise)
Common
Affects 1 in 10 to 1 in 100 people
- Bruising (ecchymosis) at the injection site
- Fever (≥38°C / 100.4°F)
- Joint pain (arthralgia)
- Nausea
- Sweating
- Chills (shivering)
Uncommon
Affects 1 in 100 to 1 in 1,000 people
- Swollen lymph nodes (lymphadenopathy)
- Flu-like symptoms
- Diarrhea
- Vomiting
- Dizziness
- Skin reactions (rash, itching)
Rare
Affects fewer than 1 in 1,000 people
- Severe allergic reactions (anaphylaxis)
- Generalized skin reactions (urticaria/hives)
- Angioedema (swelling of face, lips, tongue, or throat)
- Convulsions (seizures), including febrile seizures in children
- Neuritis (nerve inflammation)
- Vasculitis (blood vessel inflammation)
Not Known
Frequency cannot be estimated from available data
- Paraesthesia (tingling, numbness)
- Guillain-Barré Syndrome (very rare autoimmune nerve condition)
- Thrombocytopenia (reduced platelet count)
Most side effects from Foclivia are mild to moderate in severity and resolve spontaneously within 1–3 days without requiring medical treatment. Injection site reactions typically peak within 24–48 hours after vaccination and resolve within 3–5 days. Systemic symptoms (headache, fatigue, myalgia) tend to resolve within 1–2 days. These side effects are a normal indication that the immune system is responding to the vaccine.
Fever following vaccination with Foclivia is generally mild (38–39°C) and short-lived (typically resolving within 24–48 hours). High fever (>39.5°C) is uncommon. Fever is more commonly reported in children compared to adults. If fever causes discomfort, paracetamol (acetaminophen) or ibuprofen may be taken for symptomatic relief at standard doses.
Side effects may be more pronounced after the second dose compared to the first dose, which is a reflection of the primed immune response (anamnestic reaction). This is a normal and expected phenomenon and does not indicate a safety concern. Similarly, individuals who have previously been vaccinated with an H5N1 vaccine or who have pre-existing antibodies to influenza antigens may experience a stronger reactogenic response.
In clinical trials involving children, the frequency and type of side effects were generally similar to those observed in adults, with the exception that fever was more commonly reported in younger children. In the youngest age group studied (6–35 months), injection site reactions and irritability were the most frequently reported side effects. Parents and caregivers should monitor vaccinated children for these expected reactions and contact their healthcare provider if symptoms are severe, persistent, or concerning.
Seek emergency medical care immediately if you experience any signs of a severe allergic reaction after vaccination, including: difficulty breathing or wheezing, swelling of the face, lips, tongue or throat, rapid heartbeat, dizziness or collapse, or widespread skin rash with itching. These symptoms are rare but require immediate treatment. Call your local emergency number or go to the nearest emergency department.
How Should You Store Foclivia?
Foclivia must be stored in a refrigerator at a temperature between 2°C and 8°C (36°F to 46°F). Maintaining the correct cold chain is essential to preserving the potency and safety of the vaccine. The vaccine should be stored in its original packaging to protect it from light, as ultraviolet radiation can degrade the vaccine antigens and the MF59 adjuvant emulsion.
Do not freeze Foclivia. Freezing irreversibly damages the MF59 adjuvant emulsion, causing it to separate into its component phases (squalene oil droplets and aqueous phase). A frozen and thawed vaccine may appear clumped or non-homogeneous and will not provide the intended adjuvant effect. If there is any suspicion that the vaccine has been frozen, it must be discarded and not administered. Healthcare facilities should use temperature monitoring devices in vaccine storage refrigerators and establish clear protocols for handling temperature excursions.
Prior to administration, the vaccine should be allowed to reach room temperature (approximately 15–20 minutes out of the refrigerator) and then gently shaken to resuspend the contents. The vaccine should appear as a milky white, uniform suspension. Do not use the vaccine if it contains particles, if the suspension cannot be resuspended by gentle shaking, or if the appearance is otherwise abnormal.
The multi-dose presentation of Foclivia contains the preservative thiomersal (thimerosal). Once a multi-dose vial has been first opened (punctured), it should be used within the period specified in the product information (typically within 24 hours when stored at 2–8°C). The pre-filled syringe presentation does not contain preservatives and is intended for single use only. Any unused vaccine or waste material should be disposed of in accordance with local requirements for biological waste.
Keep Foclivia out of the sight and reach of children. Do not use the vaccine after the expiry date stated on the label and carton. As the vaccine is administered by healthcare professionals in clinical settings, patients generally do not need to handle or store the vaccine themselves. However, if you are transporting the vaccine (for example, between healthcare facilities), ensure that it is kept in an appropriate cold chain container with temperature indicators.
What Does Foclivia Contain?
Active Ingredient
The active ingredient in Foclivia is influenza virus surface antigens (haemagglutinin and neuraminidase) from the pandemic influenza strain A/Vietnam/1194/2004 (H5N1), propagated in embryonated hen’s eggs. Each 0.5 mL dose contains 7.5 micrograms of haemagglutinin (HA), which is the primary immunogenic component of the vaccine. The viral antigens are purified by zonal centrifugation and inactivated with formaldehyde, then further purified to obtain the surface antigens (a “subunit” vaccine). Because only the surface proteins are included (not the whole virus), the vaccine cannot cause influenza infection.
Adjuvant
Foclivia contains the MF59C.1 adjuvant, an oil-in-water emulsion composed of:
- Squalene: 9.75 mg per dose. A naturally occurring organic compound found in the human body and many foods. It is the principal active component of the adjuvant.
- Polysorbate 80: 1.175 mg per dose. An emulsifier (surfactant) that stabilizes the oil-in-water emulsion.
- Sorbitan trioleate: 1.175 mg per dose. A co-surfactant that contributes to the stability of the MF59 nanoemulsion.
Excipients (Inactive Ingredients)
The aqueous phase of Foclivia contains the following buffer salts and excipients:
- Sodium chloride
- Potassium chloride
- Potassium dihydrogen phosphate
- Disodium phosphate dihydrate
- Magnesium chloride hexahydrate
- Calcium chloride dihydrate
- Sodium citrate
- Citric acid
- Water for injections
Trace Residuals
Due to the manufacturing process, Foclivia may contain trace amounts of the following substances:
- Egg proteins (ovalbumin): The vaccine is produced in embryonated chicken eggs. Although extensive purification removes the vast majority of egg protein, trace quantities may remain. This is relevant for individuals with severe egg allergy.
- Neomycin and kanamycin: Antibiotics used during the manufacturing process to prevent bacterial contamination. Residual amounts are present in trace quantities.
- Barium sulfate: Used during the purification process.
- Formaldehyde: Used to inactivate the virus. Residual trace amounts may be present.
- Cetyltrimethylammonium bromide (CTAB): A detergent used during the antigen purification process.
The multi-dose vial presentation of Foclivia also contains thiomersal (thimerosal) as a preservative. Thiomersal is an organomercury compound that prevents bacterial contamination of multi-dose vials. The single-dose pre-filled syringe does not contain thiomersal. The World Health Organization’s Global Advisory Committee on Vaccine Safety (GACVS) has consistently concluded that there is no evidence that thiomersal at the levels used in vaccines poses a health risk, and its benefits in multi-dose vials (preventing potentially fatal bacterial contamination) clearly outweigh any theoretical risks.
Frequently Asked Questions About Foclivia
Foclivia is specifically designed for pandemic influenza caused by the H5N1 avian influenza virus, whereas seasonal flu vaccines target the influenza strains (typically H1N1, H3N2, and influenza B lineages) that circulate in the general population each year. Foclivia contains the MF59 adjuvant, which enables a lower antigen dose to produce a stronger immune response — critical for maximizing vaccine supply during a pandemic. Additionally, Foclivia requires two doses for primary vaccination, while seasonal flu vaccines typically require only one dose for most adults. Foclivia is authorized as a mock-up pandemic vaccine and would only be deployed when a pandemic is officially declared, while seasonal flu vaccines are used annually.
Yes, the MF59 adjuvant has an extensive safety record. It has been used in influenza vaccines since 1997 (initially in Fluad, a seasonal influenza vaccine for the elderly) and has been administered to more than 100 million individuals worldwide. Extensive post-marketing surveillance and multiple independent safety reviews have confirmed that MF59-adjuvanted vaccines have a safety profile comparable to non-adjuvanted influenza vaccines, with the main difference being slightly higher rates of mild, transient local injection site reactions. Long-term follow-up studies have not identified any increased risk of autoimmune disorders or other chronic conditions associated with MF59-containing vaccines.
No, it is impossible to get avian influenza from Foclivia. The vaccine contains only purified surface proteins (haemagglutinin and neuraminidase) from the H5N1 virus, not the complete live or attenuated virus. The manufacturing process involves growing the virus in eggs, then inactivating it with formaldehyde, and finally extracting and purifying only the surface antigens. Without the viral genetic material and internal proteins needed for replication, the vaccine components cannot cause infection. The most common side effects (injection site soreness, mild fever, fatigue) are caused by the immune system’s response to the vaccine, not by infection.
Because H5N1 has not caused a widespread pandemic in humans, the clinical effectiveness of Foclivia cannot be directly measured against natural infection in large populations. Instead, effectiveness is inferred from immunogenicity data — the vaccine’s ability to produce protective antibody levels. In clinical trials, Foclivia met the stringent CHMP immunogenicity criteria, with more than 70% of vaccinated adults achieving seroprotective antibody titers after the two-dose primary series. Additionally, the MF59 adjuvant has been shown to induce cross-reactive antibodies that may provide some protection against antigenically drifted H5N1 variants. However, if the actual pandemic strain differs significantly from the vaccine strain, the manufacturer may need to update the antigen.
Foclivia is designed to protect against the H5N1 subtype of avian influenza. It is not expected to provide significant protection against other avian influenza subtypes such as H7N9, H5N6, H5N8, or H9N2, as these viruses have different haemagglutinin and neuraminidase proteins. However, the MF59 adjuvant does broaden the immune response somewhat, and cross-reactive antibodies against related H5 clade variants have been demonstrated. If a pandemic were caused by a different influenza subtype, a separate vaccine targeting that specific strain would need to be developed. The mock-up authorization framework allows for rapid strain changes within the same vaccine platform.
H5N1 avian influenza viruses have not circulated widely in humans, so the vast majority of the population has no pre-existing immunity to this subtype. With seasonal influenza, most adults have some baseline immunity from prior infections and vaccinations with related strains, so a single vaccine dose is sufficient to “boost” this existing immunity. For H5N1, the first dose of Foclivia primes the immune system (introducing the antigen and initiating the primary immune response), while the second dose boosts the response to protective levels. This two-dose “prime-boost” strategy is standard for vaccines against novel pathogens to which the population is immunologically naïve.
References
- European Medicines Agency (EMA). Foclivia – Summary of Product Characteristics. Last updated 2024. Available at: EMA EPAR: Foclivia
- World Health Organization (WHO). Antigenic and genetic characteristics of zoonotic influenza A viruses and development of candidate vaccine viruses for pandemic preparedness. Weekly Epidemiological Record. 2024;99(10):111-128.
- European Centre for Disease Prevention and Control (ECDC). Risk assessment: Avian influenza A(H5N1) – multi-country outbreak assessment. Updated 2025.
- Banzhoff A, Gasparini R, Laghi-Pasini F, et al. MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS ONE. 2009;4(2):e4384.
- Vesikari T, Forstén A, Arora A, Tsai T, Clemens R. Influenza vaccination in children primed with MF59-adjuvanted or non-adjuvanted seasonal influenza vaccine. Human Vaccines & Immunotherapeutics. 2015;11(8):2102-2112.
- O’Hagan DT, Ott GS, Nest GV, Rappuoli R, Giudice GD. The history of MF59 adjuvant: a phoenix that arose from the ashes. Expert Review of Vaccines. 2013;12(1):13-30.
- World Health Organization (WHO). Global Advisory Committee on Vaccine Safety (GACVS). Statement on thiomersal. Updated 2023.
- Pellegrini M, Nicolay U, Lindert K, Grber N, Della Cioppa G, Vesikari T. MF59-adjuvanted versus non-adjuvanted influenza vaccines: integrated analysis from a large safety database. Vaccine. 2009;27(49):6959-6965.
- Nicholson KG, Colegate AE, Podda A, et al. Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza. The Lancet. 2001;357(9272):1937-1943.
- World Health Organization (WHO). Pandemic influenza preparedness and response: A WHO guidance document. 2009 (with 2023 updates).
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