Live attenuated and inactivated influenza vaccines in children

Abstract

Background: Live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are available for children. Local and systemic immunity induced by LAIV followed a month later by LAIV and IIV followed by LAIV were investigated with virus recovery after LAIV doses as surrogates for protection against influenza on natural exposure.

Methods: Fifteen children received IIV followed by LAIV, 13 an initial dose of LAIV, and 11 a second dose of LAIV. The studies were done during autumn 2009 and autumn 2010 with the same seasonal vaccine (A/California/07/09 [H1N1], A/Perth/16/09 [H3N2], B/Brisbane/60/08).

Results: Twenty-eight of 39 possible influenza viral strains were recovered after the initial dose of LAIV. When LAIV followed IIV, 21 of 45 viral strains were identified. When compared to primary LAIV infection, the decreased frequency of shedding with the IIV-LAIV schedule was significant (P = .023). With LAIV-LAIV, the fewest viral strains were recovered (3/33)--numbers significantly lower (P < .001) than shedding after initial LAIV and after IIV-LAIV (P < .001). Serum hemagglutination inhibition antibody responses were more frequent after IIV than LAIV (P = .02). In contrast, more mucosal immunoglobulin A responses were seen with LAIV.

Conclusions: LAIV priming induces greater inhibition of virus recovery on LAIV challenge than IIV priming. The correlate(s) of protection are the subject of ongoing analysis.

Clinical trials registration: NCT01246999.

Keywords: children; influenza; vaccines.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Amount of virus recovered by strain with different schedules. A–C, Titer of virus recovered on days 2, 4, and 7 with influenza H1N1, H3N2, and B, respectively, after trivalent live attenuated influenza virus (LAIV). The response to initial dose of LAIV is shown in the blue diamonds. The response to LAIV given after inactivated influenza vaccine is represented by red squares and the response to a second dose of LAIV by green triangles. Horizontal lines represent the geometric mean titer of virus shed, and the continuous horizontal dotted line represents the lower limit of detection with negative values assigned a value one-half the lower limit of detection. D, Composite of all strains recovered. When values were identical, they are shown as superimposed on each other. Abbreviation: PFU, plaque-forming unit.

Figure 2.

Viral shedding over time by vaccination regimen. Points indicate the percentage of viruses of any subtype recovered in culture at each time point for each vaccination group. Lines indicate Poisson regression estimates, which demonstrate that live attenuated influenza virus (LAIV) shedding with the initial dose (blue line) is significantly greater than after the second LAIV dose (green line) (P < .001); that LAIV shedding after inactivated influenza vaccine (IIV; red line) is significantly lower than after the initial LAIV dose (blue line) (P < .001), and that LAIV shedding after LAIV (green line) and after IIV (red line) are not significantly different (P = .098).

Figure 3.

The magnitude of hemagglutination inhibition (HAI) titer as a function of age at time of vaccination is shown with only influenza B showing a significant rise with age. H1 vs age: Pearson correlation coefficient = 0.11; P = .540; H3 vs age: Pearson correlation coefficient = 0.31; P = .080; B vs age: Pearson correlation coefficient = 0.46; P = .007.