BIMERVAX XBB.1.16
Recombinant protein-based COVID-19 vaccine (XBB.1.16 variant) – booster for adults
BIMERVAX XBB.1.16 is a recombinant protein-based COVID-19 booster vaccine developed by HIPRA Human Health. It targets the Omicron XBB.1.16 subvariant and is authorized for use as a booster dose in individuals aged 16 years and older. This guide covers its uses, dosage, potential side effects, storage requirements, and important safety information based on EMA and WHO guidelines.
Quick Facts
Key Takeaways
- BIMERVAX XBB.1.16 is a protein subunit COVID-19 vaccine that uses a recombinant spike protein from the Omicron XBB.1.16 variant combined with a squalene-based adjuvant (SQBA).
- It is authorized as a booster dose for individuals aged 16 years and older, regardless of their primary vaccination series.
- The most common side effects are injection site pain, fatigue, headache, and myalgia, which are typically mild and resolve within 1–3 days.
- The vaccine does not contain live virus, mRNA, or genetic material – it uses a well-established protein subunit platform similar to hepatitis B and influenza vaccines.
- Storage is straightforward at 2–8°C (standard refrigerator temperature), with no ultra-cold chain requirements.
What Is BIMERVAX XBB.1.16 and What Is It Used For?
BIMERVAX XBB.1.16 is a next-generation COVID-19 vaccine developed by the Spanish biotechnology company HIPRA Human Health S.L.U. Unlike mRNA-based vaccines such as those from Pfizer-BioNTech and Moderna, BIMERVAX uses a recombinant protein subunit approach. This means the vaccine delivers a laboratory-produced version of the SARS-CoV-2 spike protein directly to the immune system, rather than relying on the body's cells to manufacture it from genetic instructions.
The active substance in BIMERVAX XBB.1.16 is a recombinant fusion heterodimer protein derived from the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, specifically engineered to match the XBB.1.16 Omicron subvariant. This protein is produced using Chinese hamster ovary (CHO) cell technology, a well-established manufacturing platform used for decades in the production of various biologic medicines and vaccines.
The vaccine is formulated with SQBA, a squalene-based oil-in-water adjuvant. Adjuvants are substances added to vaccines to enhance the body's immune response. The squalene-based adjuvant in BIMERVAX works by creating a local inflammatory environment at the injection site, recruiting immune cells and improving antigen presentation. This adjuvant technology has a long safety track record in seasonal influenza vaccines administered to millions of people worldwide.
BIMERVAX XBB.1.16 received its marketing authorization from the European Medicines Agency (EMA) as an adapted COVID-19 booster vaccine. The EMA's Committee for Medicinal Products for Human Use (CHMP) recommended the vaccine based on immunogenicity data demonstrating a robust neutralizing antibody response against the XBB.1.16 variant, as well as cross-neutralizing activity against other circulating Omicron subvariants. The vaccine is intended for use as part of ongoing vaccination campaigns to maintain population-level immunity against COVID-19.
The protein subunit platform offers several practical advantages. Because BIMERVAX does not contain mRNA or viral genetic material, it can be stored at standard refrigerator temperatures (2–8°C) without the need for ultra-cold storage infrastructure. This makes distribution and administration considerably simpler, particularly in settings where cold chain logistics are challenging. The technology is also familiar to healthcare providers who have extensive experience with other protein-based vaccines, including hepatitis B, pertussis, and recombinant influenza vaccines.
What Should You Know Before Receiving BIMERVAX XBB.1.16?
Contraindications
BIMERVAX XBB.1.16 must not be administered to individuals who have experienced a severe allergic reaction (anaphylaxis) to the active substance or to any of the excipients listed in the vaccine composition. If you experienced a serious allergic reaction after a previous dose of any COVID-19 vaccine, discuss this with your healthcare provider before receiving BIMERVAX XBB.1.16.
There are no specific age-related contraindications beyond the authorized age range. However, the vaccine has not been studied in children below 16 years of age, and therefore its use in this population is not currently recommended. Individuals with a history of severe allergic reactions to other vaccines or injectable therapies should be assessed carefully, although a history of allergies that are not related to vaccine components is generally not a contraindication.
Anaphylaxis has been reported rarely following COVID-19 vaccination. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following vaccine administration. Individuals should be observed for at least 15 minutes after vaccination.
Warnings and Precautions
Vaccination should be postponed in individuals who have an acute severe febrile illness or acute infection. The presence of a minor infection or low-grade fever should not delay vaccination. Healthcare providers should exercise caution when administering the vaccine to individuals with thrombocytopenia or any bleeding disorder, as bleeding or bruising may occur following an intramuscular injection.
As with all vaccines, BIMERVAX XBB.1.16 may not fully protect all vaccinated individuals, and the duration of protection is not yet fully established. Immunocompromised individuals, including those receiving immunosuppressive therapy, may have a diminished immune response to the vaccine. This does not contraindicate vaccination but means that additional doses or alternative strategies may be needed, as determined by a healthcare provider.
There have been very rare reports of myocarditis and pericarditis following COVID-19 vaccination with other platforms. While no specific signal has been identified for protein subunit COVID-19 vaccines, healthcare providers and vaccine recipients should be aware of the signs and symptoms of myocarditis and pericarditis, including chest pain, shortness of breath, and palpitations. Seek medical attention immediately if these symptoms develop after vaccination.
Anxiety-related reactions, including vasovagal reactions (fainting), hyperventilation, and stress-related reactions, may occur in association with the vaccination process. This is more common in younger adults and does not represent an allergic reaction to the vaccine itself. Healthcare facilities should have measures in place to prevent injury from fainting.
Pregnancy and Breastfeeding
There is limited clinical data on the use of BIMERVAX XBB.1.16 during pregnancy. Preclinical (animal) studies have not indicated direct or indirect harmful effects on pregnancy, embryo-fetal development, parturition, or postnatal development. However, as a precautionary measure, the decision to vaccinate during pregnancy should be made on an individual basis after careful consideration of the potential benefits and risks.
The World Health Organization (WHO) recommends that pregnant individuals at high risk of severe COVID-19 (due to comorbidities or occupational exposure) should be offered COVID-19 vaccination. The European Medicines Agency notes that the use of BIMERVAX XBB.1.16 during pregnancy should be considered in accordance with national recommendations.
It is not known whether BIMERVAX XBB.1.16 is excreted in human breast milk. However, based on the nature of the vaccine (non-replicating protein subunit), a risk to breastfed infants is considered unlikely. Breastfeeding individuals should discuss the timing of vaccination with their healthcare provider.
How Does BIMERVAX XBB.1.16 Interact with Other Medicines?
As a non-replicating protein subunit vaccine, BIMERVAX XBB.1.16 has a low potential for drug interactions compared to live vaccines. The active substance (recombinant spike protein) and adjuvant are processed locally and do not interact with hepatic drug metabolism pathways, meaning pharmacokinetic interactions with oral medications are not expected.
However, certain categories of medicines can influence the immune response to BIMERVAX XBB.1.16. Immunosuppressive medications, including high-dose corticosteroids, chemotherapeutic agents, biologic disease-modifying agents, and other immunomodulators, may reduce the antibody response to the vaccine. This does not mean vaccination should be avoided in these patients; rather, the timing of vaccination relative to treatment cycles may need to be optimized in consultation with a specialist.
Co-administration studies of BIMERVAX with seasonal influenza vaccines have been conducted. Data suggest that simultaneous administration at different injection sites does not compromise the immune response to either vaccine and does not increase the overall frequency of adverse events beyond what would be expected from each vaccine given separately. This supports the practical approach of offering both vaccines during the same clinical visit, particularly during autumn and winter vaccination campaigns.
| Medicine/Category | Type of Interaction | Clinical Significance | Recommendation |
|---|---|---|---|
| Immunosuppressants (e.g., methotrexate, azathioprine) | Reduced vaccine efficacy | Moderate | Time vaccination with treatment cycles; may need additional dose |
| High-dose corticosteroids (≥20 mg/day prednisone) | Reduced immune response | Moderate | Vaccinate; consider additional dose after immunosuppression ends |
| Biologic DMARDs (e.g., rituximab, anti-TNF agents) | Reduced antibody response | High (especially rituximab) | Vaccinate at least 4 weeks before next cycle if possible |
| Anticoagulants (e.g., warfarin, heparin) | Increased bleeding risk at injection site | Low | Use fine needle; apply pressure for 2 minutes post-injection |
| Influenza vaccines | No interference | None | Can be co-administered at different injection sites |
| Other non-live vaccines (e.g., pneumococcal) | No expected interference | Low | Can generally be given concomitantly or with any interval |
Patients receiving anticoagulant therapy (such as warfarin, direct oral anticoagulants, or heparin) can safely receive BIMERVAX XBB.1.16. However, as with any intramuscular injection, there is a small increased risk of bleeding or hematoma at the injection site. Healthcare providers should use a fine-gauge needle and apply firm pressure to the injection site for at least two minutes without rubbing.
What Is the Correct Dosage of BIMERVAX XBB.1.16?
Adults (16 Years and Older)
Standard Booster Dose
Dose: 0.5 mL (40 micrograms of recombinant SARS-CoV-2 spike protein RBD)
Route: Intramuscular injection, preferably into the deltoid muscle of the upper arm
Schedule: Single booster dose, administered at least 3 months after the last COVID-19 vaccine dose or confirmed SARS-CoV-2 infection
BIMERVAX XBB.1.16 is formulated as a ready-to-use emulsion for injection supplied in multi-dose vials. Each vial contains 5 doses of 0.5 mL. Before withdrawing each dose, the vial should be gently swirled (not shaken vigorously) to ensure a uniform, milky-white emulsion. Do not use the vaccine if it contains visible particles, appears discolored, or if the vial is damaged.
The vaccine should be administered by a healthcare professional trained in vaccination technique. The preferred injection site is the deltoid muscle of the non-dominant arm. The vaccine must not be injected intravenously, subcutaneously, or intradermally. After withdrawing the dose, it should be administered promptly, as the vaccine does not contain a preservative.
Children and Adolescents
Pediatric Use
BIMERVAX XBB.1.16 is not currently authorized for use in children under 16 years of age. Clinical data in this population are insufficient. For children and adolescents who require COVID-19 vaccination, other authorized vaccines should be used in accordance with national recommendations.
Elderly
No dose adjustment is required for elderly individuals. Clinical studies included participants aged 65 years and older, and the vaccine demonstrated an acceptable safety and immunogenicity profile in this age group. Older adults, particularly those with comorbidities, are among the highest priority groups for COVID-19 booster vaccination due to their increased risk of severe disease.
Immunocompromised Individuals
The standard dose of 0.5 mL applies to immunocompromised individuals. However, the immune response may be reduced. National guidelines in several countries recommend that severely immunocompromised individuals receive additional booster doses at shorter intervals, as determined by their treating physician. This decision should be based on the individual's level of immunosuppression and ongoing risk of exposure.
Missed Dose
If a scheduled booster vaccination is missed or delayed, it should be administered as soon as possible. There is no need to restart the vaccination course. The immune system retains immunological memory from prior COVID-19 vaccination, and a delayed booster dose will still effectively stimulate an anamnestic (recall) response.
Overdose
No cases of overdose have been reported in clinical studies. In the event that more than the recommended dose is inadvertently administered, the individual should be monitored for any adverse reactions. There is no specific antidote. Treatment should be supportive and directed toward managing any symptoms that may occur. Overdose events should be reported to the relevant pharmacovigilance authorities.
| Population | Dose | Route | Notes |
|---|---|---|---|
| Adults (16–64 years) | 0.5 mL (40 µg) | Intramuscular (deltoid) | Single booster dose; ≥3 months after last dose/infection |
| Elderly (≥65 years) | 0.5 mL (40 µg) | Intramuscular (deltoid) | No dose adjustment; high-priority group |
| Immunocompromised | 0.5 mL (40 µg) | Intramuscular (deltoid) | Standard dose; may need additional doses per national guidance |
| Children (<16 years) | Not authorized | – | Use alternative authorized COVID-19 vaccine |
What Are the Side Effects of BIMERVAX XBB.1.16?
Like all vaccines, BIMERVAX XBB.1.16 can cause side effects, although not everyone experiences them. The side effects observed in clinical trials were consistent with those expected from protein subunit vaccines with oil-in-water adjuvants and were generally less frequent and less intense than those reported with mRNA COVID-19 vaccines. Most adverse reactions were mild to moderate in severity and resolved spontaneously within a few days.
The safety profile has been evaluated in several clinical trials involving thousands of participants across different age groups and geographic regions. Post-authorization safety monitoring continues through pharmacovigilance systems in all countries where the vaccine is approved. The following frequency categories are based on clinical trial data and post-marketing surveillance reports.
Very Common
- Injection site pain or tenderness
- Fatigue
- Headache
- Myalgia (muscle pain)
Common
- Injection site swelling or redness
- Fever (pyrexia ≥38°C)
- Chills
- Arthralgia (joint pain)
- Nausea
- Malaise (general feeling of being unwell)
Uncommon
- Lymphadenopathy (swollen lymph nodes)
- Dizziness
- Pruritus (itching at injection site)
- Diarrhea
- Insomnia
- Excessive sweating
Rare
- Anaphylaxis or severe allergic reactions
- Facial swelling (in individuals with a history of dermal filler injections)
- Paresthesia (tingling or numbness)
- Hypersensitivity reactions
Injection site reactions are the most commonly reported side effect, with pain at the injection site affecting more than half of vaccinated individuals. The pain is typically described as mild and does not usually interfere with daily activities. It usually begins within hours of injection and resolves within 24 to 48 hours. Application of a cool compress and use of paracetamol (acetaminophen) can help manage discomfort if needed.
Systemic side effects such as fatigue, headache, and myalgia tend to occur within the first 24 hours after vaccination and resolve within 1 to 3 days. Fever is less common with BIMERVAX XBB.1.16 than with mRNA vaccines and, when present, is usually low-grade (below 39°C). These systemic reactions are a normal sign that the body's immune system is responding to the vaccine.
Post-marketing surveillance data from the European Medicines Agency's EudraVigilance database and national pharmacovigilance authorities have not identified any new safety signals beyond those observed in clinical trials. As with all COVID-19 vaccines, ongoing monitoring for very rare events, including myocarditis, pericarditis, and immune-mediated conditions, continues through routine pharmacovigilance activities.
Contact your healthcare provider or seek emergency care if you experience any of the following after vaccination: signs of a severe allergic reaction (difficulty breathing, swelling of the face and throat, rapid heartbeat, dizziness, generalized rash); persistent high fever (>40°C); chest pain, shortness of breath, or palpitations; severe headache that does not respond to over-the-counter pain relief; or any symptom that concerns you.
How Should You Store BIMERVAX XBB.1.16?
BIMERVAX XBB.1.16 should be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). The vaccine must not be frozen. If the vaccine has been accidentally frozen, it must be discarded. Frozen and subsequently thawed vaccine should never be administered, as freezing can damage the adjuvant emulsion and alter the vaccine's immunogenic properties.
The vaccine vials should be kept in the outer carton at all times to protect from light. Exposure to sunlight or fluorescent lighting can degrade the protein antigen and reduce vaccine potency. The unopened vials have a shelf life of 9 months when stored at the recommended temperature, as indicated on the product label and outer carton.
Once the multi-dose vial has been punctured for the first time, it should be used within 6 hours. During this in-use period, the vial may be stored at temperatures up to 25°C (77°F). Any remaining vaccine in the vial after 6 hours must be discarded. Each time a dose is withdrawn, the vial should be gently swirled to resuspend any settled material.
Healthcare facilities should maintain temperature logs for vaccine storage units and have contingency plans for power outages or refrigerator malfunctions. Vaccines that have been exposed to temperatures outside the recommended range should not be administered until guidance has been obtained from the manufacturer or public health authorities regarding stability data.
- Temperature: 2–8°C (standard refrigerator)
- Protection: Keep in outer carton; protect from light
- Do not freeze: Discard if frozen
- After opening: Use within 6 hours; may store up to 25°C during use
- Shelf life: 9 months (unopened, properly stored)
What Does BIMERVAX XBB.1.16 Contain?
Active Substance
The active substance is a recombinant SARS-CoV-2 spike protein receptor-binding domain (RBD) fusion heterodimer based on the XBB.1.16 Omicron subvariant. Each 0.5 mL dose contains 40 micrograms of this protein. The antigen is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells, a well-characterized expression system widely used in biopharmaceutical manufacturing for its ability to produce properly folded and glycosylated proteins.
Adjuvant
BIMERVAX XBB.1.16 contains the proprietary SQBA adjuvant, a squalene-based oil-in-water emulsion. The adjuvant components include:
- Squalene: A naturally occurring oil found in shark liver and plant sources (olives). It serves as the core component of the oil-in-water emulsion.
- Polysorbate 80: An emulsifier that stabilizes the oil-in-water formulation.
- Sorbitan trioleate: A surfactant that contributes to emulsion stability.
This type of adjuvant system is well-established in vaccinology, with a long track record of safe use in influenza vaccines (such as MF59 in Fluad). The adjuvant works by creating a depot effect at the injection site, recruiting innate immune cells and enhancing antigen uptake and presentation, ultimately leading to a stronger and more durable adaptive immune response.
Other Ingredients (Excipients)
- Sodium chloride (salt, for isotonicity)
- Disodium hydrogen phosphate dodecahydrate (buffer)
- Sodium dihydrogen phosphate dihydrate (buffer)
- Water for injections
BIMERVAX XBB.1.16 does not contain preservatives, latex, egg proteins, or antibiotics. The vaccine is formulated as a milky-white emulsion for injection. The appearance is characteristic of squalene-based adjuvanted vaccines and is normal.
The vaccine does not contain egg, gelatin, latex, or common food allergens. Individuals with known allergies to polysorbate 80 should discuss this with their healthcare provider before vaccination, as polysorbate 80 is an excipient in the formulation. Cross-reactivity between polysorbate 80 and polyethylene glycol (PEG) has been reported very rarely.
Frequently Asked Questions
BIMERVAX XBB.1.16 is a recombinant protein-based COVID-19 vaccine developed by HIPRA Human Health. It is authorized as a booster dose for individuals aged 16 years and older who have previously received a COVID-19 vaccine. It contains a laboratory-produced version of the SARS-CoV-2 spike protein based on the Omicron XBB.1.16 variant, combined with a squalene-based adjuvant to enhance the immune response. Unlike mRNA vaccines, it does not contain genetic material.
BIMERVAX uses protein subunit technology, which delivers a pre-made spike protein directly to the immune system, rather than using mRNA to instruct cells to produce it. This platform has been used successfully for decades in vaccines like hepatitis B and influenza. Key practical advantages include simpler storage at standard refrigerator temperatures (2–8°C) and a familiar safety profile. In clinical studies, BIMERVAX tended to cause fewer systemic side effects (such as fever) compared to mRNA boosters, though injection site reactions were similar.
The most common side effects are injection site pain (affects more than 1 in 2 recipients), fatigue, headache, and muscle pain. These are typically mild to moderate in intensity and resolve within 1 to 3 days without treatment. Fever occurs less frequently than with mRNA vaccines and is usually low-grade. These reactions are a normal sign that the immune system is responding to the vaccine. Over-the-counter pain relievers such as paracetamol can be used if needed.
There is limited clinical data for use during pregnancy, but animal studies have not shown harmful effects. The WHO recommends that pregnant individuals at high risk of severe COVID-19 should be offered vaccination. The decision should be made individually with your healthcare provider, weighing potential benefits against risks. Breastfeeding is not considered a contraindication, as the non-replicating nature of the vaccine poses no expected risk to the infant.
BIMERVAX XBB.1.16 should be stored in a refrigerator at 2–8°C (36–46°F), protected from light in the original carton. It must not be frozen – if accidentally frozen, the vaccine must be discarded. Once a multi-dose vial is first punctured, it should be used within 6 hours. The unopened shelf life is 9 months at proper storage temperature.
Yes, co-administration studies show that BIMERVAX XBB.1.16 can be given at the same visit as seasonal influenza vaccines, as long as they are administered at different injection sites (e.g., one in each arm). The immune response to both vaccines is maintained, and the overall side effect profile is not substantially different from receiving each vaccine separately. This makes it convenient for healthcare systems to offer both during autumn/winter campaigns.
References
- European Medicines Agency (EMA). BIMERVAX (COVID-19 Vaccine, recombinant, adjuvanted) – Summary of Product Characteristics. Last updated 2025. Available at: EMA BIMERVAX EPAR.
- HIPRA Human Health S.L.U. BIMERVAX XBB.1.16 – Package Leaflet and Product Information. 2024.
- European Centre for Disease Prevention and Control (ECDC). Interim public health considerations for COVID-19 vaccination in the EU/EEA for the 2024/2025 season. ECDC Technical Report, 2024.
- World Health Organization (WHO). COVID-19 Vaccines: Technical Documents. WHO Interim Recommendations on the Use of Protein Subunit COVID-19 Vaccines. 2024.
- Sanz I, Galadi-Enríquez P, Ramos-Seví M, et al. Immunogenicity and Safety of BIMERVAX as a Heterologous Booster Vaccine: A Phase IIb/III Randomized Clinical Trial. The Lancet Infectious Diseases. 2023;23(11):1264–1275.
- Committee for Medicinal Products for Human Use (CHMP). Assessment Report: BIMERVAX. European Medicines Agency. EMA/CHMP/2024.
- Voysey M, Clemens SAC, Madhi SA, et al. Safety and Efficacy of the ChAdOx1 nCoV-19 Vaccine (AZD1222) against SARS-CoV-2: An Interim Analysis of Four Randomised Controlled Trials in Brazil, South Africa, and the UK. The Lancet. 2021;397(10269):99–111. (Background reference on COVID-19 vaccine development).
- Heath PT, Galiza EP, Baxter DN, et al. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N Engl J Med. 2021;385:1172–1183. (Comparative reference on protein subunit COVID-19 vaccines).
- WHO Expert Committee on Biological Standardization. Guidelines on Clinical Evaluation of Vaccines: Regulatory Expectations. WHO Technical Report Series No. 1024. 2023.
- British National Formulary (BNF). COVID-19 Vaccines. National Institute for Health and Care Excellence (NICE). 2025.
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