Improving the efficacy of influenza vaccine in children

Improving the efficacy of influenza vaccine in children

Influenza infection can be associated with severe complications and hospitalization in young children. Vaccination of children is safe and may substantially reduce disease burden and influenza transmission within the community.

However, the trivalent inactivated influenza vaccine (TIV) is poorly immunogenic and has low effectiveness under 2 y of age. Furthermore, two doses of TIV ≥1 mo apart are required for protection for the first year of immunization.

The availability of novel adjuvants provides a potential solution toward effective influenza control in the first 2 y. MF59 is an oil-in-water squalene-based adjuvant currently licensed for use in many countries worldwide for >65-y-old adults and in Canada for 6- to 24-mo-old children. Clinical trials have shown MF59- based influenza vaccines to be safe and to induce significantly enhanced, longer lasting, as well as broader immune responses compared with nonadjuvanted split vaccines. Importantly the adjuvanted vaccine was shown to be significantly more efficacious than nonadjuvanted vaccines in preventing influenza infection in 6- to 72-mo-old children.

This difference is thought to be mediated by MF59-mediated improved recruitment and activation of antigen presenting cells (APCs), activation of vaccine specific CD4+ T lymphocytes, and spreading of the neutralizing sites recognized by specific antibodies. MF59-adjuvanted TIV is not currently licensed for use in children, but has been administered to over 5,000 children in clinical trials and showed enhanced immunogenicity and efficacy compared with TIV. No previous studies have attempted to assess the molecular mechanisms underlying influenza vaccine-induced immunity in children under 2 y of age.

Researchers conducted a phase II open-label, randomized controlled trial of adjuvanted and nonadjuvanted TIV in 90 healthy 14- to 24-month-old children during the winter of 2012–2013.

Taking a systems biology approach, the authors measured the magnitude and kinetics of antibody generation, production of vaccine-specific CD4+ T cells, and gene expression signatures in response to vaccination.

Compared with TIV, the adjuvanted vaccine boosted serum antibody levels, immune response kinetics, and levels of CD4+ T cells that secreted multiple cytokines, including TNF-α and IL-2, which are involved in antiviral immunity.

Adding the adjuvant increased the consistency and robustness of gene expression tied to antigen presentation and antiviral immunity; the adjuvant also shifted vaccination-associated gene expression in the children to adult-like patterns.

According to the authors, in addition to uncovering molecular correlates of vaccine-induced immunity in children, the findings underscore the role of the MF59 adjuvant in improving the efficacy of seasonal influenza vaccination in children.