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Clinical Trial
. 2021 Apr;204(1):125-133.
doi: 10.1111/cei.13564. Epub 2021 Jan 13.

Pre-existing influenza-specific nasal IgA or nasal viral infection does not affect live attenuated influenza vaccine immunogenicity in children

M E Cole  1 , R Kundu  2   3 , A F Abdulla  1 , N Andrews  4 , K Hoschler  4 , J Southern  4 , D Jackson  4 , E Miller  4 , M Zambon  4 , P J Turner  2   3 , J S Tregoning  1   2
Affiliations
Clinical Trial

Pre-existing influenza-specific nasal IgA or nasal viral infection does not affect live attenuated influenza vaccine immunogenicity in children

M E Cole et al. Clin Exp Immunol. 2021 Apr.

Abstract

The United Kingdom has a national immunization programme which includes annual influenza vaccination in school-aged children, using live attenuated influenza vaccine (LAIV). LAIV is given annually, and it is unclear whether repeat administration can affect immunogenicity. Because LAIV is delivered intranasally, pre-existing local antibody might be important. In this study, we analysed banked samples from a study performed during the 2017/18 influenza season to investigate the role of pre-existing influenza-specific nasal immunoglobulin (Ig)A in children aged 6-14 years. Nasopharyngeal swabs were collected prior to LAIV immunization to measure pre-existing IgA levels and test for concurrent upper respiratory tract viral infections (URTI). Oral fluid samples were taken at baseline and 21-28 days after LAIV to measure IgG as a surrogate of immunogenicity. Antibody levels at baseline were compared with a pre-existing data set of LAIV shedding from the same individuals, measured by reverse transcription-polymerase chain reaction. There was detectable nasal IgA specific to all four strains in the vaccine at baseline. However, baseline nasal IgA did not correlate with the fold change in IgG response to the vaccine. Baseline nasal IgA also did not have an impact upon whether vaccine virus RNA was detectable after immunization. There was no difference in fold change of antibody between individuals with and without an URTI at the time of immunization. Overall, we observed no effect of pre-existing influenza-specific nasal antibody levels on immunogenicity, supporting annual immunization with LAIV in children.

Keywords: IgA; LAIV; influenza; mucosal; schoolchildren.

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Conflict of interest statement

The authors have no competing interests.

Figures

Fig. 1
Fig. 1
Study outline and recruitment. (a) Schematic of sampling in study participants. (b) Recruitment, retention and analysis of volunteers in the study.
Fig. 2
Fig. 2
Baseline nasal immunoglobulin (Ig)A does not impact antibody response to vaccine. Nasal and oral swabs were collected prior to live attenuated influenza vaccine (LAIV) immunization. (a) Influenza strain‐specific IgA was measured in nasal swabs. (b) Influenza strain‐specific IgG was measured in oral swabs. Fold change in IgG specific for H1 (c) and H3 (d) were compared with baseline IgA. Points represent individuals; numbers above IgA are individuals with detectable IgA. *P < 0·05, *** =P < 0·001.
Fig. 3
Fig. 3
Baseline nasal immunoglobulin (Ig)A does not correlate with vaccine viral shedding. Baseline antibody titres prior to live attenuated influenza vaccine (LAIV) vaccination in nasal (a–d) fluids were grouped according to whether the vaccine virus RNA was detectable in nasal samples on days 1, 3 or 6 after immunization. Responses were compared to the matched virus in the vaccine. Points represent individual samples; dashed lines represent means.
Fig. 4
Fig. 4
Underlying upper respiratory tract infections do not alter vaccine immunogenicity. An additional nasal swab was collected from a subset of children (n = 83) to detect pre‐existing infections prior to live attenuated influenza vaccine (LAIV). Proportion of RNA‐positive swabs and virus type detected (a). Fold change in immunoglobulin (Ig)G specific for H1 (b) and H3 (c) were compared in children with and without co‐infection.
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