Introduction
Influenza, commonly known as the flu, poses a significant health risk worldwide, particularly among children and adolescents. This age group not only suffers considerable illness and hospitalizations due to influenza but also plays a key role in transmitting the virus within communities. Vaccination remains the cornerstone of preventive strategies against influenza. Over the past two decades, two main types of influenza vaccines have been widely used among children and adolescents: Live Attenuated Influenza Vaccines (LAIV) and Inactivated Influenza Vaccines (IIV). A recent comprehensive review and meta-analysis spanning from 2003 to 2023 sheds light on how effective these vaccines are in the real world, helping parents, clinicians, and health professionals make informed decisions about flu prevention for young populations.
Why Focus on Children and Adolescents for Influenza Vaccination?
Children and adolescents are particularly vulnerable to influenza because their immune systems are still developing, and they typically experience higher rates of flu illness and complications than healthy adults. Moreover, schools and daycare settings offer ample opportunities for the virus to spread rapidly. Vaccinating children not only protects them but also reduces transmission to more vulnerable populations, such as the elderly or those with chronic health conditions.
The Two Main Types of Influenza Vaccines
Live Attenuated Influenza Vaccine (LAIV)
LAIV contains weakened live viruses that do not cause disease but stimulate a natural immune response. It is usually administered as a nasal spray, making it needle-free and often preferred by children and parents averse to injections. LAIV was first approved for use in children in 2003.
Inactivated Influenza Vaccine (IIV)
IIV contains killed virus particles and is administered by injection. It stimulates immunity without introducing live virus and has been a longstanding option for influenza prevention in different age groups including children.
Challenges in Influenza Vaccine Effectiveness
Influenza viruses are characterized by frequent mutations and a high degree of variability, especially the hemagglutinin (HA) and neuraminidase (NA) surface proteins. This means the viral strains circulating each flu season differ from year to year. Vaccine production begins approximately six months before the flu season, based on predictions of which strains will predominate. Occasionally, mismatches occur between vaccine strains and circulating viruses, leading to reduced vaccine effectiveness (VE).
For this reason, the World Health Organization (WHO) reviews global influenza surveillance data biannually and recommends the virus strains to be included in vaccines for each hemisphere’s flu season. National bodies such as the U.S. Advisory Committee on Immunization Practices (ACIP) and the UK Joint Committee on Vaccination and Immunisation (JCVI) decide on vaccine recommendations accordingly.
Historical Context of LAIV Recommendations
Following the 2009 influenza A (H1N1) pandemic, several U.S.-based studies observed that the LAIV provided poor protection against this particular H1N1 strain during the 2013-2016 seasons. Consequently, the U.S. ACIP halted recommending LAIV for the 2016-17 and 2017-18 seasons.
In response, the LAIV manufacturer improved the strain selection and virus manufacturing techniques to better match circulating H1N1 strains. These enhancements led to the reinstatement of LAIV recommendations starting with the 2018-2019 season and continuing reliably thereafter.
The 2025 Systematic Literature Review and Meta-Analysis
A group of researchers conducted a systematic review and meta-analysis compiling 109 studies published from 2003 through the 2022-23 influenza season. Their goal was to evaluate and compare the real-world effectiveness of LAIV and IIV in preventing laboratory-confirmed influenza illness among children and adolescents under 18 years of age in Northern Hemisphere countries.
Methodology in Brief
– Studies were rigorously screened for design quality and relevance.
– Analyses were stratified across three time periods to reflect changes in influenza virus circulation and vaccine formulations:
1. 2003-04 to 2008-09 (pre-2009 H1N1 pandemic)
2. 2010-11 to 2016-17 (post-pandemic, pre-improved LAIV strain)
3. 2017-18 to 2022-23 (post-improved LAIV strain)
– Two meta-analysis techniques were utilized:
– Random effects meta-analysis to estimate absolute vaccine effectiveness (aVE), illustrating protection compared with no vaccination.
– Network meta-analysis to estimate relative vaccine effectiveness (rVE) of LAIV compared to IIV.
– Results were expressed with 95% confidence intervals to indicate estimate precision.
Main Findings
Absolute Vaccine Effectiveness—LAIV and IIV Compared to No Vaccine
Both LAIV and IIV showed approximately 50% effectiveness at preventing influenza illness across all time periods studied. This means vaccination reduces the risk of flu illness by about half compared to unvaccinated children.
Relative Vaccine Effectiveness—LAIV Compared to IIV
– Between 2010-11 and 2016-17, LAIV offered significantly lower protection against influenza A (H1N1), showing about 46% less effectiveness than IIV.
– Following improvements to the LAIV strain formulation starting in 2017-18, LAIV and IIV demonstrated similar protection levels against influenza A (H1N1), with no statistically significant difference.
– For influenza A (any subtype), LAIV and IIV had comparable effectiveness after 2017 (rVE near zero).
– Notably, for influenza B viruses during the same latter period, LAIV was more effective than IIV, with an estimated relative vaccine effectiveness gain of approximately 196%, a significant advantage.
Implications for Parents and Healthcare Providers
This comprehensive review confirms that both LAIV and IIV are effective options for protecting children and adolescents from seasonal influenza. The findings emphasize the following points:
– Influenza vaccination—regardless of vaccine type—meaningfully reduces the risk of flu illness in children.
– The live attenuated vaccine, especially post-2017 improvements, performs comparably to the inactivated vaccine for most influenza strains, and may offer enhanced protection against influenza B.
– Vaccine recommendations may change over time based on surveillance and effectiveness data, underscoring the importance of following guidance from trusted public health authorities.
A Patient Scenario: Emily’s Flu Vaccination Experience
Emily, an 8-year-old girl from Ohio, had previously been hesitant about flu vaccines due to fear of needles. Her mother was relieved to learn that the nasal spray LAIV was available and recommended by their pediatrician. After the 2018 improvements to LAIV, Emily’s doctor explained that the nasal spray vaccine works well and is preferred by many children. Emily received the vaccine without distress, and her mother felt reassured knowing Emily was protected during flu season. This scenario illustrates the benefits of having multiple vaccine options that cater to children’s preferences and needs.
Addressing Common Misconceptions
1. Misconception: The flu vaccine gives you the flu.
Fact: Neither LAIV nor IIV contains a fully active influenza virus capable of causing flu illness.
2. Misconception: The flu vaccine doesn’t work because flu viruses change.
Fact: While the effectiveness varies yearly due to viral changes, vaccination still significantly reduces the risk of severe illness and complications.
3. Misconception: Only injectable vaccines are effective.
Fact: LAIV has been shown to be similarly effective and may be preferable for needle-averse children.
Expert Recommendations
Leading health authorities like the CDC endorse annual influenza vaccination as the best protection for children. The choice between LAIV and IIV should be based on availability, age eligibility, underlying health conditions, and patient preference. Healthcare providers should stay updated on vaccine effectiveness data and evolving guidelines.
Conclusion
The updated evidence from 20 years of research underscores that both live attenuated and inactivated influenza vaccines provide valuable protection to children and adolescents against influenza. The enhancements made to LAIV formulations have restored its role as a safe and effective option. Annual vaccination remains vital for preventing flu morbidity in young populations and curtailing community transmission. Parents and clinicians can be confident that either vaccine type administered appropriately is a practical choice to protect children’s health during flu seasons.
References
1. Stuurman AL, Enxing J, Gutiérrez AV, et al. Real-world Effectiveness of Live Attenuated and Inactivated Influenza Vaccines in Children and Adolescents from 2003 to 2023: a Plain Language Summary of Publication. Ther Adv Infect Dis. 2025 Oct 17;12:20499361251390680.
2. Centers for Disease Control and Prevention. Influenza Vaccination: A Summary for Clinicians. https://www.cdc.gov/flu/professionals/vaccination/index.htm
3. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2023 southern hemisphere influenza season. https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-in-the-2023-southern-hemisphere-influenza-season
4. Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022–23 Influenza Season. MMWR Recomm Rep. 2022;71(1):1–28.
5. 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):685-695.
Funding
This research and the related plain language summary were sponsored by AstraZeneca, supporting improved understanding of influenza vaccine effectiveness in pediatric populations.
