Nuvaxovid XBB.1.5

What Is Nuvaxovid XBB.1.5 and What Is It Used For?

Nuvaxovid XBB.1.5 is an adapted COVID-19 vaccine manufactured by Novavax, an American biotechnology company, with European distribution and release testing performed by Novavax CZ a.s. in the Czech Republic. The vaccine is based on a well-established recombinant protein platform and was developed as an updated version of the original Nuvaxovid COVID-19 vaccine, reformulated to specifically target the XBB.1.5 Omicron subvariant of SARS-CoV-2 that circulated widely during 2023 and remains genetically similar to more recent circulating strains.

The active substance in Nuvaxovid XBB.1.5 is a full-length recombinant SARS-CoV-2 spike glycoprotein, engineered to match the amino acid sequence of the XBB.1.5 variant. Unlike vaccines that use only the receptor-binding domain (RBD), Nuvaxovid presents the entire prefusion-stabilized spike protein, preserving a wide array of immunogenic epitopes. This protein is produced in Sf9 moth cells using a baculovirus expression system, a technology with a decades-long track record in producing biologic products including the recombinant influenza vaccine Flublok.

The vaccine is formulated with Matrix-M, a proprietary saponin-based adjuvant derived from the bark of the Chilean soap bark tree (Quillaja saponaria Molina). Matrix-M is composed of two distinct saponin fractions combined with cholesterol and phospholipids that self-assemble into nanoparticle structures. The adjuvant enhances the innate immune response, recruits antigen-presenting cells to the injection site, and promotes both strong antibody and T-cell responses. Matrix-M has been used in multiple vaccine programs and has an extensive safety profile from clinical and post-marketing data.

The European Medicines Agency (EMA) authorized Nuvaxovid XBB.1.5 as an adapted vaccine through its variation procedure, based on immunogenicity data demonstrating a robust neutralizing antibody response against the XBB.1.5 variant and cross-neutralizing activity against related Omicron subvariants. The U.S. Food and Drug Administration (FDA) granted emergency use authorization and subsequent Biologics License Application (BLA) approval for the updated formulation. National regulatory agencies worldwide, including the UK Medicines and Healthcare products Regulatory Agency (MHRA), Health Canada, and the Australian Therapeutic Goods Administration (TGA), have followed similar authorization pathways.

Nuvaxovid XBB.1.5 is used as part of ongoing COVID-19 vaccination strategies to maintain protective immunity in populations at risk of severe COVID-19. It can be used both as a primary series in individuals who have not previously been vaccinated and as a booster dose in those who have previously received any authorized COVID-19 vaccine. For people who experienced significant reactogenicity with mRNA vaccines or who prefer a non-mRNA alternative, Nuvaxovid provides an evidence-based option. Clinical trials and real-world effectiveness studies have consistently shown protection against symptomatic infection, hospitalization, and severe disease.

The protein subunit approach used in Nuvaxovid offers several notable practical advantages. Because the vaccine contains no mRNA, no lipid nanoparticles, and no viral genetic material, it can be stored at standard refrigerator temperatures of 2–8°C without the ultra-cold storage chains required by some mRNA vaccines. This simplifies distribution and administration, particularly in primary care settings, community pharmacies, and lower-resource settings. The technology is also conceptually familiar to healthcare providers and the public, resembling other routinely used vaccines such as hepatitis B, acellular pertussis, and human papillomavirus (HPV) vaccines.

What Should You Know Before Receiving Nuvaxovid XBB.1.5?

Contraindications

Nuvaxovid XBB.1.5 must not be administered to individuals who have experienced a severe allergic reaction (anaphylaxis) to the active substance or to any of the excipients in the formulation. Known contraindications include severe hypersensitivity to the Matrix-M adjuvant components, polysorbate 80, or sodium metabisulfite. If you experienced a serious allergic reaction after a previous dose of Nuvaxovid or any other COVID-19 vaccine, discuss this with your healthcare provider before receiving Nuvaxovid XBB.1.5.

The vaccine has not been studied in children under 12 years of age, and therefore use in this population is not currently authorized. For pediatric COVID-19 vaccination below 12 years, alternative authorized vaccines should be used in line with national immunization programs. Individuals with a history of severe allergic reactions to other vaccines or injectable therapies should be assessed carefully; a history of environmental or food allergies unrelated to vaccine components is generally not a contraindication.

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, common cold, 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, Nuvaxovid XBB.1.5 may not fully protect all vaccinated individuals, and the duration of protection is not yet definitively established. Real-world effectiveness data indicate that protection against symptomatic infection wanes over several months, while protection against severe disease appears more durable. Booster doses at appropriate intervals, guided by national immunization authorities, may be recommended to maintain protection, particularly in those at higher risk of severe disease.

Immunocompromised individuals, including those receiving immunosuppressive therapy, solid organ transplant recipients, patients with certain hematologic cancers, and those with advanced HIV, may develop a diminished immune response to the vaccine. This does not contraindicate vaccination; rather, these individuals may benefit from additional doses or alternative dosing strategies, as determined by their specialist healthcare provider.

Cases of myocarditis and pericarditis have been reported very rarely following COVID-19 vaccination, predominantly with mRNA vaccines. Post-marketing surveillance of Nuvaxovid has identified rare cases of myocarditis and pericarditis, most often occurring within 14 days of vaccination and more commonly in younger males. Healthcare providers and vaccine recipients should be aware of the signs and symptoms of myocarditis and pericarditis, which include chest pain, shortness of breath, and palpitations. Anyone experiencing such symptoms after vaccination should seek prompt medical evaluation.

Anxiety-related reactions, including vasovagal reactions (fainting), hyperventilation, or stress-related responses, may occur in association with the vaccination process itself. These reactions are more common in adolescents and young adults and do not represent an allergic reaction to the vaccine. Healthcare facilities should have measures in place to prevent injury from fainting, including seated or supine vaccination for those with a history of such reactions.

Capillary leak syndrome has been reported very rarely after Nuvaxovid vaccination. Individuals with a history of capillary leak syndrome should discuss the risks and benefits of vaccination with their healthcare provider, as they may be at increased risk of recurrence. Symptoms such as rapid swelling of arms and legs, sudden weight gain, and lightheadedness should prompt immediate medical attention.

Pregnancy and Breastfeeding

Clinical data on the use of Nuvaxovid XBB.1.5 during pregnancy are limited but growing through ongoing pregnancy registries and real-world surveillance. Preclinical (animal) studies with the original Nuvaxovid and its adjuvant have not indicated direct or indirect harmful effects on pregnancy, embryo-fetal development, parturition, or postnatal development. The XBB.1.5 adaptation involves only a change in the spike protein sequence and is not expected to alter the overall safety profile during pregnancy.

The World Health Organization (WHO) and most national immunization advisory groups recommend COVID-19 vaccination in pregnant individuals, particularly those at higher risk of severe COVID-19 due to age, comorbidities (such as diabetes, obesity, or chronic cardiopulmonary disease), or occupational exposure. COVID-19 during pregnancy is associated with an increased risk of severe maternal illness and adverse pregnancy outcomes including preterm birth. The decision to use Nuvaxovid XBB.1.5 in pregnancy should be made in consultation with a healthcare provider, weighing individual risk and benefit.

It is not known whether Nuvaxovid XBB.1.5 is excreted in human breast milk. However, based on the non-replicating nature of the vaccine and the limited systemic absorption of its components, a risk to breastfed infants is considered unlikely. Maternal antibodies produced in response to vaccination are transferred through breast milk and may contribute to passive immunity in the infant. Breastfeeding individuals can generally receive the vaccine when clinically indicated.

Fertility

Animal reproduction studies have shown no effect of Nuvaxovid on female fertility. Available clinical data do not suggest any effect on male or female fertility. Numerous large-scale studies of COVID-19 vaccines have specifically investigated fertility outcomes, including sperm parameters, menstrual regularity, ovarian reserve, and conception rates after assisted reproductive techniques, and have consistently found no association between vaccination and reduced fertility.

How Does Nuvaxovid XBB.1.5 Interact with Other Medicines?

As a non-replicating protein subunit vaccine, Nuvaxovid XBB.1.5 has a low potential for drug interactions compared to live attenuated vaccines or small-molecule medications. The active substance (recombinant spike protein) and Matrix-M adjuvant are processed locally at the injection site and within regional lymph nodes and are not metabolized through hepatic cytochrome P450 pathways. Therefore, pharmacokinetic interactions with oral medications, including warfarin, direct oral anticoagulants, statins, and common antihypertensives, are not expected.

However, certain categories of medicines can influence the immune response to Nuvaxovid XBB.1.5. Immunosuppressive medications, including high-dose systemic corticosteroids, cytotoxic chemotherapeutic agents, biologic disease-modifying antirheumatic drugs (DMARDs), and targeted immunomodulators, may reduce the antibody and cellular 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. For example, vaccination at least 2 weeks before initiating immunosuppression, when clinically feasible, is often associated with better immunogenicity.

Co-administration studies of Nuvaxovid with seasonal inactivated influenza vaccines have been conducted. Data suggest that simultaneous administration at separate injection sites does not meaningfully compromise the immune response to either vaccine, although a modest reduction in neutralizing antibody response to the spike protein has been observed in some studies. The overall adverse event profile with co-administration is consistent with what would be expected from each vaccine given individually, and the practical benefit of a single clinical visit typically outweighs the modest immunological difference for most people.

Major Interactions

The most clinically significant interactions involve agents that broadly suppress the adaptive immune system. B-cell depleting therapies such as rituximab (used for lymphoma and autoimmune diseases) substantially reduce antibody responses to Nuvaxovid XBB.1.5, sometimes for 6–12 months after the last dose. When possible, vaccination should be timed before starting such therapies or at least 4–6 weeks before a scheduled infusion. Specialty societies including the American College of Rheumatology and the European Alliance of Associations for Rheumatology (EULAR) have published detailed guidance for vaccination timing in immunosuppressed patients.

Minor Interactions

Minor interactions typically relate to increased local reactions or marginal changes in immune response. Patients receiving anticoagulant therapy can safely receive Nuvaxovid XBB.1.5, but healthcare providers should use a fine-gauge needle (typically 23–25 gauge) and apply firm, sustained pressure for at least 2 minutes without rubbing to minimize the risk of hematoma or bleeding at the injection site. Paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) can be taken to manage post-vaccination symptoms but should not be routinely taken prophylactically before vaccination, as this may theoretically reduce immunogenicity.

What Is the Correct Dosage of Nuvaxovid XBB.1.5?

Adults (18 Years and Older)

Nuvaxovid XBB.1.5 is supplied as a ready-to-use dispersion for injection in multi-dose vials, each typically containing 10 doses of 0.5 mL. The vial should be gently swirled (not shaken) before each dose is withdrawn to ensure a uniform colorless to slightly yellow dispersion. Do not use the vaccine if it contains particulates, appears discolored, or if the vial is damaged or has exceeded its in-use period.

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 Nuvaxovid XBB.1.5 does not contain a preservative.

Adolescents (12 to 17 Years)

Children (Under 12 Years)

Elderly (65 Years and Older)

No dose adjustment is required for elderly individuals. Clinical studies and post-marketing data include large numbers of adults aged 65 years and older, and the vaccine has demonstrated an acceptable safety and immunogenicity profile in this age group. Older adults, particularly those with comorbidities such as cardiovascular disease, chronic lung disease, diabetes, or chronic kidney disease, are among the highest priority groups for COVID-19 vaccination due to their substantially increased risk of severe disease, hospitalization, and death.

Immunocompromised Individuals

The standard dose of 0.5 mL applies to immunocompromised individuals. However, the immune response may be reduced, sometimes substantially. Many national guidelines recommend that severely immunocompromised individuals receive additional doses at shorter intervals, for example a 3-dose primary series followed by earlier and more frequent boosters. This decision should be based on the individual's level and type of immunosuppression, their ongoing risk of exposure, and guidance from their treating specialist.

Missed or Delayed Dose

If a scheduled vaccination is missed or delayed, it should be administered as soon as possible. There is no need to restart a vaccination course from the beginning. The immune system retains immunological memory from prior COVID-19 vaccination or infection, and a delayed dose will still effectively stimulate an anamnestic (recall) response. National schedules may need to be adjusted based on individual risk factors.

Overdose

No specific cases of overdose have been systematically reported. In the event that more than the recommended dose is inadvertently administered (for example, through a dispensing or drawing-up error), the individual should be monitored for any adverse reactions, particularly more pronounced local or systemic reactogenicity. There is no specific antidote. Treatment should be supportive and directed toward managing any symptoms. Overdose events should be reported to the relevant pharmacovigilance authorities.

What Are the Side Effects of Nuvaxovid XBB.1.5?

Like all vaccines, Nuvaxovid XBB.1.5 can cause side effects, although not everyone who receives it will experience them. The side effects observed in clinical trials and post-marketing surveillance are consistent with those expected from protein subunit vaccines containing saponin-based adjuvants. Most adverse reactions are mild to moderate in severity and resolve spontaneously within a few days without specific treatment.

The overall reactogenicity of Nuvaxovid is generally lower than that observed with mRNA COVID-19 vaccines, particularly for systemic reactions such as fever, chills, and intense fatigue. This is a factor some patients consider when choosing a COVID-19 vaccine, especially those who had significant reactions to previous mRNA doses. The safety profile has been evaluated in clinical trials involving more than 50,000 participants across multiple countries and age groups, and continues to be monitored through pharmacovigilance programs worldwide.

Injection site reactions are the most commonly reported side effect, with tenderness or pain affecting about half of vaccine recipients. The discomfort is typically described as mild and is often most noticeable for 24 to 48 hours after injection. It rarely interferes with daily activities and can be managed with cool compresses and simple analgesics such as paracetamol (acetaminophen) if desired. Redness and swelling at the injection site occur in a smaller proportion of recipients and typically resolve within 2–3 days.

Systemic side effects such as headache, fatigue, and myalgia tend to occur within the first 24 hours after vaccination and generally resolve within 1 to 2 days. Fever with Nuvaxovid is less frequent than with mRNA vaccines; when it occurs, it is usually low-grade (below 39°C) and brief. In real-world data, approximately 5–10% of recipients experience a fever following Nuvaxovid, compared to 15–25% with mRNA boosters. These systemic reactions represent normal immune activation.

Post-marketing surveillance data from the European Medicines Agency's EudraVigilance database, the U.S. Vaccine Adverse Event Reporting System (VAERS), and the WHO's VigiBase have identified rare cases of myocarditis and pericarditis following Nuvaxovid vaccination. The reporting rate appears lower than with mRNA vaccines but is not zero. Most cases have occurred in younger males within 14 days of vaccination, typically presenting as chest pain or shortness of breath, and have been self-limiting with supportive care.

Very rare cases of capillary leak syndrome have been reported in post-authorization monitoring, some in individuals with a prior history of the condition. Symptoms include rapid-onset swelling of the extremities, hypotension, and hemoconcentration. This has prompted a specific warning and contraindication in individuals with a history of capillary leak syndrome in the product information.

How Should You Store Nuvaxovid XBB.1.5?

Nuvaxovid XBB.1.5 should be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). The vaccine must not be frozen at any stage of distribution or storage. If the vaccine has been accidentally frozen, it must be discarded. Frozen and then thawed vaccine should never be administered, as freezing can disrupt the Matrix-M adjuvant nanoparticle structure and damage the recombinant spike protein, altering immunogenicity.

The vaccine vials should be kept in the outer carton at all times to protect from light. Direct exposure to sunlight or prolonged exposure to fluorescent lighting can degrade the protein antigen and potentially reduce vaccine potency. The unopened vials typically have a shelf life of 9 months when stored at the recommended temperature, as indicated on the product label and outer carton. Do not use the vaccine after the expiration date printed on the vial.

Once the multi-dose vial has been punctured for the first time, it may be stored at temperatures between 2°C and 25°C and should be used within 12 hours. Any remaining vaccine in the vial after this in-use period must be discarded. Each time a dose is withdrawn, the vial should be gently swirled to maintain a uniform dispersion. Written documentation of the first puncture time and the expiration time should be maintained.

Healthcare facilities should maintain continuous temperature logs for vaccine storage units and have contingency plans for power outages, refrigerator malfunctions, or transport excursions. 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 for the specific excursion conditions. Temperature monitoring devices meeting WHO and national regulatory specifications should be used.

Unused or expired vaccine should be disposed of in accordance with local pharmaceutical waste management regulations. Multi-dose vials contain no preservative and should not be used beyond the specified in-use period even if doses remain. Safe disposal is important to prevent accidental exposure and environmental contamination.

What Does Nuvaxovid XBB.1.5 Contain?

Active Substance

The active substance is a recombinant full-length SARS-CoV-2 spike glycoprotein based on the Omicron XBB.1.5 subvariant. Each 0.5 mL dose contains 5 micrograms of the purified, prefusion-stabilized spike protein. The antigen is produced using recombinant DNA technology in Spodoptera frugiperda (Sf9) insect cell culture using a baculovirus expression system. The protein is self-assembled into nanoparticles, presenting multiple copies of the spike trimer in a configuration that resembles the conformation of spike protein on the authentic virus surface.

Matrix-M Adjuvant

Nuvaxovid XBB.1.5 contains the proprietary Matrix-M adjuvant at a dose of 50 micrograms per 0.5 mL. Matrix-M is a saponin-based adjuvant derived from the bark of the Chilean soap bark tree (Quillaja saponaria Molina). It consists of two distinct saponin fractions (Fraction A and Fraction C) combined with cholesterol and phospholipid to self-assemble into approximately 40-nanometer open-cage nanoparticles.

Matrix-M works by stimulating the innate immune system at the injection site and in the draining lymph nodes. It enhances antigen uptake by antigen-presenting cells such as dendritic cells, promotes the migration of these cells to lymphoid tissues, and supports the development of a robust T-cell response in addition to antibody production. The adjuvant has been used in multiple vaccine development programs, including the R21/Matrix-M malaria vaccine, which has been recommended by the WHO for use in children in malaria-endemic areas.

Other Ingredients (Excipients)

• Disodium hydrogen phosphate heptahydrate: buffer system
• Sodium dihydrogen phosphate monohydrate: buffer system
• Sodium chloride: maintains isotonicity
• Polysorbate 80: surfactant for protein stabilization
• Sodium hydroxide (for pH adjustment)
• Hydrochloric acid (for pH adjustment)
• Water for injections

Nuvaxovid XBB.1.5 does not contain preservatives, thimerosal (mercury-containing compounds), aluminum adjuvants, latex, human or animal-derived components, egg proteins, or common food allergens. The final formulation is presented as a colorless to slightly yellow dispersion for intramuscular injection.