Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

Influenza vaccine effectiveness can be reduced in older adults and among repeatedly vaccinated groups. Results from year 1 of “PIVOT,” a randomized trial among adults aged ≥65 years in Hong Kong, showed that adjuvanted (Adj), high-dose (HD), and recombinant hemagglutinin (rHA) vaccines induced greater antibody responses against vaccine viruses than standard-dose (SD) influenza vaccine. Here, we examine the breadth of A(H3N2)-reactive antibodies induced during the first 2 study years (2017/2018, 2018/2019), and compare participants who received influenza vaccination annually, or not at all, for 5 years preceding enrollment.

14–20 PIVOT participants per vaccine and prior vaccination group (0/5 or 5/5 prior years) who provided sera on days 0, 30, and 182 in year 1 and days 0 and 30 in year 2 were assessed. Hemagglutination inhibition (HAI) antibody titers were measured against 30 viruses spanning 1968 to 2018.

In year 1, rHA and Adj but not HD vaccines induced titers ≥40 and titer rises ≥4-fold (seroconversion) against significantly more strains than SD vaccine among participants vaccinated 0/5 prior years. Only rHA and Adj vaccines induced titers ≥40 against post-vaccine strains. Antibody responses were poor among participants vaccinated 5/5 compared with 0/5 prior years and only rHA increased the breadth of seroconversion compared with the SD vaccine in this group. Antibody responses were weaker across groups in year 2.

The results suggest that Adj and particularly rHA vaccines may improve the breadth of protection against A(H3N2) viruses but may not overcome attenuating effects of repeated vaccination in older adults.

NCT03330132

What is this summary about? This is a plain language summary describing the results of a systematic literature review and meta-analysis originally published in Expert Review of Vaccines in July 2025. Children and adolescents are an important group for influenzavaccination because they play a major role in spreading influenza viruses to others and are often hospitalized due to influenza . Live attenuated influenza vaccines (LAIV) and inactivated influenza vaccines (IIV) are two different types of influenzavaccine that are used to protect children and adolescents from influenza illness. This review looked at how well LAIV and IIV provided protection against influenza between 2003 (when LAIV was first available) and 2023 in children and adolescents under 18 years of age. Why was this review done?Influenza viruses can change rapidly in ways that affect how well vaccines work in a particular influenza season . When this happens, influenza vaccines may not provide good protection because they take many months to produce, with development starting about 6 months before the influenza season begins. The specific versions of influenza viruses, or strains, used to make vaccines change from year to year based on recommendations from The World Health Organization . Public health bodies such as the United States’ ‘Advisory Committee on Immunization Practices’ (US ACIP) and the United Kingdom’s ‘Joint Committee on Vaccination and Immunisation’ also publish recommendations on which vaccines should be used for the upcoming influenza season on their respective websites and will update these recommendations for the next influenza season if studies show that a particular vaccine isn’t providing enough protection. For this reason, influenza vaccines can lose their recommendation for use or other vaccines may be recommended instead for use in select groups. For example, the US ACIP stopped recommending LAIV for the 2016–17 and 2017–18 influenza seasons after some US-based studies showed it didn’t protect well against the influenza A (H1N1) virus following the 2009 influenza A (H1N1) pandemic. However, an updated LAIV was developed that improved on the strain selection process and contained a replacement influenza A (H1N1) strain. This led to LAIV being recommended by the committee again for the 2018–2019 influenza season, and LAIV has continued to be recommended by the committee in its seasonal vaccine guidance each year since 2019. The researchers carried out this review to look at how well LAIV and IIV protected against influenza in children and adolescents in real-world settings (e.g. outside clinical trials) since LAIV was first approved in 2003. How was this review carried out? The researchers found studies of LAIV and IIV vaccine effectiveness (VE) published in scientific journals or by public health bodies and screened the results to only include studies meeting pre-defined criteria for study design and quality. The results were examined per influenza season and also by three time periods based on influenza A (H1N1) and LAIV history to understand how well LAIV and IIV protected against influenza during each period: • 2003–04 to 2008–09: Before the 2009 influenza A (H1N1) pandemic. • 2010–11 to 2016–17: After the 2009 pandemic and before the improved LAIV strain selection process.• 2017–18 to 2022–23: After the improved LAIV strain selection process. The researchers then used two different types of meta-analysis to combine the findings from multiple studies together to create a single result, or summary estimate, of VE for LAIV and IIV to help to understand how well both types of vaccine protected against any influenza illness and against influenza illness caused by specific influenza viruses, for example influenza A (H1N1), A (H3N2), and B: • A random effects meta-analysis was used to estimate absolute vaccine effectiveness (aVE) – this is a measure of how a vaccine protects against an illness compared with not getting a vaccine . aVE was estimated for both vaccine types (LAIV and IIV). • A network meta-analysis was used to estimate relative vaccine effectiveness (rVE) – this is a measure of how well one vaccine protects against an illness compared to another vaccine . rVE was estimated for LAIV compared to IIV. All aVE and rVE summary estimates were interpreted alongside their 95% confidence intervals , which is a range of values that shows how sure researchers are about an estimate and means the true result would fall within that range 95 times out of 100 if the study were repeated 100 times. What were the main results of this review? This review examined 109 studies from Northern Hemisphere countries with winter influenza seasons. The results showed that both LAIV and IIV were similarly effective against any influenza illness compared with not being vaccinated, with an aVE of roughly 50% in each time period. rVE estimates showed that • LAIV was less effective than IIV at protecting against influenza A (H1N1) illness between the 2010–11 and 2016–17 influenza seasons (rVE=−46%; 95% confidence interval: −57% to −33%). • Following improvements to the LAIV strain selection process introduced in the 2017–18 season, both vaccines provided similar levels of protection against influenza A (H1N1) illness between 2017–18 and 2022–23, (rVE=10%; 95% confidence interval: −35% to 87%). • During the same period, LAIV and IIV were similarly effective at protecting against illness from any influenza A virus (rVE=7%; 95% confidence interval: –15% to 33%). • LAIV was also more effective than IIV against illness from any influenza B virus after the improved strain selection process (rVE=196%; 95% confidence interval: 73% to 406%). What do these results mean? These findings show that LAIV and IIV offer similar protection against any influenza illness in children and adolescents under 18 years of age, and that getting vaccinated with any influenzavaccine will provide protection against influenza illness. Who should read this summary? This summary is intended for parents considering vaccinating their children against influenza , healthcare professionals who do not specialize in influenza but vaccinate people against influenza in their medical practice, and for individuals who wish to learn about the level of protection provided by influenzavaccination . Who sponsored this research and plain language summary?This research and this plain language summary were both sponsored by AstraZeneca.