Immunogenicity and safety of MF59-adjuvanted and full-dose unadjuvanted trivalent inactivated influenza vaccines among vaccine-naïve children in a randomized clinical trial in rural Senegal

Abstract

Introduction: Effective, programmatically suitable influenza vaccines are needed for low-resource countries.

Materials and methods: This phase II, placebo-controlled, randomized safety and immunogenicity trial (NCT01819155) was conducted in Senegal using the 2012-2013 Northern Hemisphere trivalent influenza vaccine (TIV) formulation. Participants were allocated in a 2:2:1 ratio to receive TIV (full-dose for all age groups), adjuvanted TIV (aTIV), or placebo. Participants were stratified into age groups: 6-11, 12-35, and 36-71 months. All participants were vaccine-naïve and received two doses of study vaccine 4 weeks apart. The two independent primary objectives were to estimate the immunogenicity of TIV and of aTIV as the proportion of children with a hemagglutination inhibition (HI) antibody titer of ≥1:40 to each vaccine strain at 28 days post-dose two. Safety was evaluated by solicited local and systemic reactions, unsolicited adverse events, and serious adverse events.

Results: 296 children received TIV, aTIV, or placebo, and 235 were included in the final analysis. After two doses, children aged 6-11, 12-35, and 36-71 months receiving TIV had HI titers ≥1:40 against A/H1N1 (73.1%, 94.1%, and 97.0%), A/H3N2 (96.2%, 100.0%, and 100.0%), and B (80.8%, 97.1%, and 97.0%), respectively. After two doses, 100% children aged 6-11, 12-35, and 36-71 months receiving aTIV had ≥1:40 titers against A/H1N1, A/H3N2, and B. After a single dose, the aTIV response was comparable to or greater than the TIV response for all vaccine strains. TIV and aTIV reactogenicity were similar, except for mild elevation in temperature (37.5-38.4 °C) which occurred more frequently in aTIV than TIV after each vaccine dose. TIV and aTIV had similarly increased pain/tenderness at the injection site compared to placebo.

Conclusions: Both aTIV and full-dose TIV were well-tolerated and immunogenic in children aged 6-71 months. These vaccines may play a role in programmatically suitable strategies to prevent influenza in low-resource settings.

Keywords: Africa; Children; Immunogenicity; Inactivated Influenza vaccine; MF59 adjuvant; Safety.

Conflict of interest statement

Conflicts of interest

Sathie Cheikh: none.

Aldiouma Diallo: none.

Bou Diarra: none.

Djibril Diene: none.

Jodi Feser: none.

Niranjan Kanesa-thasan: Was an employee with Novartis Vaccines at the time of study design and conduct.

Kathryn E Lafond: none.

Assane Ndiaye: none.

Moussa Ndiaye: none.

Tofene Ndiaye: none.

Marc-Alain Widdowson: none.

Kathleen M Neuzil: none.

Justin R Ortiz: none.

John C Victor: none.

Copyright © 2018 Elsevier Ltd. All rights reserved.

Figures

Fig. 1.

Age group specific percentages of participants with baseline seropositivity (HI titer ≥1:10) against influenza strains recommended by WHO for inclusion in 2012–2013 northern hemisphere influenza vaccines. Note: Among seropositive participants, percentages with HI titer levels ≥1:40, a level frequently considered seroprotective, are also shown.

Fig. 2.

Reverse cumulative distributions of hemagglutination inhibition antibody titers for WHO-recommended influenza strains contained in trivalent study vaccines among participants of all ages who were seronegative at baseline for the particular strain. Note: x axis is the HI titer by vaccine and antigen, and the y axis is the percentage of vaccine recipients achieving the measured HI titer.