What is the live attenuated influenza vaccine?

Live Attenuated Influenza Vaccine (LAIV)

The live attenuated influenza vaccine (LAIV) is an intranasally administered vaccine that contains live but weakened influenza viruses that are temperature-sensitive, cold-adapted, and attenuated, producing mild or no symptoms related to influenza infection. 1

Characteristics of LAIV

• LAIV was initially licensed in the United States in 2003 as a trivalent formulation (LAIV3) under the brand name FluMist, and later as a quadrivalent formulation (LAIV4) in 2012 2
• LAIV is administered intranasally, unlike inactivated influenza vaccines which are administered via intramuscular injection 1, 3
• The vaccine contains live influenza viruses that have been specifically modified to be:
  • Attenuated - producing mild or no signs or symptoms related to influenza virus infection
  • Temperature-sensitive - limited replication at 38°C-39°C, restricting the viruses from replicating efficiently in human lower airways
  • Cold-adapted - replicating efficiently at 25°C, permissive for replication of vaccine viruses but restrictive for wild-type viruses 2, 1

Mechanism of Action

• LAIV virus strains replicate primarily in nasopharyngeal epithelial cells 2
• The protective mechanisms induced by vaccination with LAIV involve both serum and nasal secretory antibodies 2, 4
• In animal studies, LAIV viruses replicate in the mucosa of the nasopharynx, inducing protective immunity against viruses included in the vaccine, but replicate inefficiently in the lower airways or lungs 2

Formulation and Development

• LAIV is developed using two stably attenuated master donor viruses (MDVs), one for type A and one for type B influenza viruses 2
• The vaccine viruses in LAIV are reassortant viruses containing genes from these MDVs that confer attenuation, temperature sensitivity, and cold adaptation, along with genes from recommended contemporary wild-type influenza viruses 2
• The vaccine is grown in embryonated hens' eggs 2
• LAIV is currently available as FluMist Quadrivalent (LAIV4), which replaced the trivalent formulation (LAIV3) during the 2013-14 influenza season 2

Approved Population

• LAIV is approved for use in healthy, non-pregnant persons aged 2 through 49 years 2, 1
• It should not be administered to children younger than 2 years or adults 50 years and older 1

Contraindications

• LAIV should not be given to:
  • Persons with a history of severe allergic reaction to any component of the vaccine or to a previous dose of any influenza vaccine 5
  • Children and adolescents receiving aspirin or salicylate-containing therapy due to the potential risk of Reye's syndrome 5
  • Immunosuppressed individuals 5
  • Children aged 2-4 years with asthma or a history of wheezing 5
  • Individuals who have received influenza antiviral medications within the recommended time frame 5
  • Healthcare personnel who work with severely immunocompromised patients 1

Effectiveness

• Before the 2009 influenza A(H1N1) pandemic, LAIV3 demonstrated superior relative efficacy compared with trivalent inactivated influenza vaccine (IIV3) among children 2, 3
• However, LAIV4 showed no statistically significant effectiveness against influenza A(H1N1)pdm09-like viruses among children during the 2013-14 and 2015-16 seasons, leading to recommendations against its use during the 2016-17 and 2017-18 seasons 2
• In February 2018, the Advisory Committee on Immunization Practices (ACIP) recommended that LAIV4 be an option for influenza vaccination for the 2018-19 season after formulation changes 2

Safety Considerations

• Recipients of LAIV may shed vaccine virus for up to 2-7 days after vaccination 1, 6
• The most common adverse events associated with LAIV are nasal congestion, headache, myalgias, or fever 3, 7
• Studies have shown an increased risk of wheezing in some young children, particularly those with a history of recurrent wheezing or reactive airways disease 3

LAIV represents an important alternative to injectable influenza vaccines, particularly for individuals who prefer a needle-free option, though its use is restricted to specific populations due to safety and effectiveness considerations.