Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis

Abstract

Background: The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA.

Methods: Before the 2013-2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated.

Results: Influenza RNA was detected in 16% fewer participants (95% CrI: -7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: -16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: -2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: -0.37, 1.26).

Conclusion: The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and -negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference.

Keywords: childhood vaccination; cystic fibrosis; influenza vaccination; live-attenuated influenza virus vaccine; viral interference.

Figure 1.

Results of the sensitivity analyses estimating the effect of measurement error in the diagnostic assays used to ascertain exposure (D0-NIRV) and outcome (detection of influenza RNA). The point and line edges represent the mean, 2.5^th and 97.5^th percentiles of the posterior distribution, respectively.

Figure 2.

Proportion of subjects with any influenza virus RNA detection (either type (A)and/or B), by study day, cystic fibrosis (CF) status and non-influenza respiratory virus (D0-NIRV) detection status on day 0 (n_{CF, D0-NIRV+} = 18, n_{CF, D0-NIRV-} = 40, n_{non-CF, D0-NIRV+} = 4, n_{non-CF, D0-NIRV-} = 13).