Efficacy, immunogenicity, and safety of a quadrivalent inactivated influenza vaccine in children aged 6-35 months: A multi-season randomised placebo-controlled trial in the Northern and Southern Hemispheres.

BACKGROUND: A quadrivalent split-virion inactivated influenza vaccine (VaxigripTetra™, Sanofi Pasteur; IIV4) containing two A strains (H1N1 and H3N2) and B strains from both lineages (Victoria and Yamagata) was approved in Europe in 2016 for individuals aged ≥ 3 years. This study examined the efficacy and safety of IIV4 in children aged 6-35 months. METHODS: This was a phase III randomised controlled trial conducted in Latin America, Asia, Africa, and Europe during the Northern Hemisphere 2014/2015 and 2015/2016 and Southern Hemisphere 2014 and 2015 influenza seasons. Healthy children aged 6-35 months not previously vaccinated against influenza were randomised to receive two full doses 28 days apart of IIV4, placebo, the licensed trivalent split-virion inactivated vaccine (IIV3), an investigational IIV3 containing a B strain from the alternate lineage. The primary objective was to demonstrate efficacy against influenza illness caused by any strain or vaccine-similar strains. RESULTS: The study enrolled 5806 participants. Efficacy, assessed in 4980 participants completing the study according to protocol, was demonstrated for IIV4. Vaccine efficacy was 50.98% (97% CI, 37.36-61.86%) against influenza caused by any A or B type and 68.40% (97% CI, 47.07-81.92%) against influenza caused by vaccine-like strains. Safety profiles were similar for IIV4, placebo, and the IIV3s, although injection-site reactions were slightly more frequent for IIV4 than placebo. CONCLUSIONS: IIV4 was safe and effective for protecting children aged 6-35 months against influenza illness caused by vaccine-similar or any circulating strains. CLINICAL TRIAL REGISTRATION: EudraCT no. 2013-001231-51.

Quadrivalent inactivated influenza vaccine (VaxigripTetra™).

INTRODUCTION: VaxigripTetra™ (IIV4; Sanofi Pasteur) is a quadrivalent split-virion influenza vaccine approved in Europe in 2016 for individuals ≥ 3 years of age. IIV4 builds on the well-established record of the trivalent split-virion influenza vaccine (Vaxigrip®). Areas covered: This literature review summarizes the rationale for developing quadrivalent influenza vaccines and discusses the phase III clinical trial results supporting the immunogenicity, safety, and tolerability of IIV4. Expert commentary: IIV4 is immunogenic and well tolerated. Adding a second B strain to the trivalent split-virion influenza vaccine provides a superior immune response for the additional strain but does not reduce the immune response for the three other strains or negatively affect the safety profile. By offering broader protection against co-circulating influenza B lineages, IIV4 has the potential to further reduce influenza-related morbidity and mortality beyond that achieved with trivalent vaccines.