What You Need to Know
The CHMP recommended removing the upper age limit from AstraZeneca’s intranasal H5N1 pandemic vaccine, which would extend eligibility from children and adolescents aged 12 months to younger than 18 years to include adults.
The vaccine has held conditional EU authorisation since May 2016 and is not licensed by the FDA or by regulators in Asia or South America.
No phase 3 trial has tested the H5N1 vaccine itself, so its approval rests on adult immunogenicity studies and phase 3 pediatric efficacy data from the seasonal live attenuated vaccine platform.
H5N1 Influenza Vaccine Background, Approval
Status
The CHMP first recommended the vaccine, then named Pandemic influenza vaccine H5N1 MedImmune, on March 31, 2016.3 The European Commission granted conditional marketing authorization on May 20, 2016, for prophylaxis of influenza in an officially declared pandemic in children and adolescents aged 12 months to younger than 18 years.3 The product took its current name on May 24, 2017.3
The vaccine contains a live attenuated reassortant A/Vietnam/1203/2004 (H5N1) strain and is built on the same components as the seasonal nasal vaccine Fluenz Tetra.3 Dosing consists of one 0.1-mL spray in each nostril, with a second dose at least 4 weeks later.3 In a declared pandemic, the H5N1 strain would be replaced with an attenuated version of the circulating pandemic strain.3
The authorization is valid throughout the EU, and the vaccine remains under additional monitoring.³
A 2025 review in The Lancet Respiratory Medicine lists the EMA as its sole licensing authority, with no approval from the US Food and Drug Administration or regulators in Asia or South America.4 Licensed H5N1 vaccines in Japan are inactivated, injectable formulations, according to the same review.4
Clinical Data Supporting the Vaccine
No phase 3 efficacy trial has tested the H5N1 vaccine itself, because the EMA notes a new pandemic live attenuated vaccine cannot be tested in children before a pandemic.3 The agency instead based its assessment on three main studies in 107 adults, plus large pediatric studies of related seasonal and pandemic live attenuated vaccines.³ Three additional studies of H7N9 and H7N7 preparedness vaccines in 170 adults showed similar results.3
Antibodies after intranasal H5N1 vaccination are difficult to measure, so investigators gave an inactivated H5N1 vaccine 3 weeks to 5 years later.3 A 4-fold antibody rise occurred in 73% (8 of 11) of primed adults vs 10% of unprimed adults.3 These adult data underpin the newly recommended removal of the upper age limit.2
The core phase 3 evidence for the platform comes from a randomized, double-blind trial of about 8000 children aged 6 to 59 months during the 2004-2005 season. Trivalent live attenuated vaccine produced 54.9% fewer culture-confirmed influenza cases than trivalent inactivated vaccine (153 vs 338 cases; P < .001). Wheezing within 42 days of dose 1 was more common with the live vaccine in previously unvaccinated infants aged 6 to 11 months (3.8% vs 2.1%; P = .076).5
The EMA noted the H5N1 vaccine might increase wheezing in children aged 1 to 2 years but judged the risk acceptable in a pandemic.³ The most common adverse events are decreased appetite, headache, rhinorrhea or nasal congestion, and malaise.³ Contraindications include severe allergy to gelatin, gentamicin, or egg proteins, although use may be appropriate in a pandemic with emergency care immediately available.³
References
Belshe RB, Edwards KM, Vesikari T, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007;356(7):685-696. doi:10.1056/NEJMoa065368
