Safety and immune responses in children after concurrent or sequential 2009 H1N1 and 2009-2010 seasonal trivalent influenza vaccinations

Abstract

Background: Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children.

Methods: Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored.

Results: All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥ 10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine.

Conclusions: Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age.

Clinical trials registration: NCT00943202.

Figures

Figure 1.

A, Rates of local symptoms by maximum severity grade as captured on the 8-day memory aid with associated 95% confidence intervals, with rate of severe response in subjects receiving first and second 2009 H1N1 influenza virus vaccinations. The numbers represent the first or second 2009 H1N1 vaccination. B, Rates of local symptoms by maximum severity grade as captured on the 8-day memory aid with associated 95% confidence intervals, with rate of severe response in subjects receiving seasonal trivalent influenza vaccine (TIV). The numbers represent the first or second 2009 H1N1 vaccination. C, Rates of systemic symptoms by maximum severity grade as captured on the 8-day memory aid with associated 95% confidence intervals, with rate of severe response. The numbers represent the first, second, or third vaccination. Abbreviations: H, 2009 H1N1 vaccine; T, TIV. The data are stratified by age and vaccine group.

Figure 2.

Geometric mean titers 21 days after each vaccination by vaccination group and age stratum for each of the 4 vaccine strains: pandemic influenza A/California/7/09 (H1N1)-like virus (H1) and seasonal trivalent influenza vaccine (TIV), comprising influenza A/Brisbane/59/2007 (H1N1)-like virus, influenza A/Brisbane/10/2007 (H3N2)-like virus, and influenza B/Brisbane/60/2008-like virus. Abbreviation: HAI, hemagglutination antibody inhibition.