Influenza A haemagglutinin specific IgG responses in children and adults after seasonal trivalent live attenuated influenza vaccination

Abstract

Influenza is a major respiratory pathogen and vaccination is the main method of prophylaxis. In 2012, the trivalent live attenuated influenza vaccine (LAIV3) was licensed in Europe for use in children. Vaccine-induced antibodies directed against the main viral surface glycoprotein, haemagglutinin (HA), play an important role in virus neutralization through different mechanism. The objective of this study was to dissect the HA specific antibody responses induced after LAIV3 immunization to the influenza A viruses in children and adults. Plasma was collected from 20 children and 20 adults pre- and post-LAIV3 vaccination (up to ayear) and analysed by the haemagglutination inhibition (HI) and ELISA assays. We found that LAIV3 boosted the HA specific IgG response against the head and the full-length of H3N2 in children, but not adults. Adults had higher levels of pre-existing stalk antibodies (towards H3N2 and H1N1), but these were not boosted by LAIV3. Importantly, we observed a trend in boosting of H1N1 HA stalk specific antibodies in children after LAIV3. Whereas, heterosubtypic H5 and H7 full-length HA specific antibodies were not boosted in either children or adults. In conclusion, LAIV3 elicited H3-head and low levels of H1 stalk specific antibody responses in children, supporting the prophylactic use of LAIV in children.

Functional immune response to influenza H1N1 in children and adults after live attenuated influenza virus vaccination

“…Several European studies showed other results, and therefore, the EU continued to recommend use of LAIV in children . We have previously shown that LAIV immunization did not boost H1N1 HI titres in adults or children . Although children had significantly higher H1N1 HI titres than adults prior to and up to 56 days after vaccination, probably due to previous infection or the pandemic vaccination during the 2009 mass vaccination campaign.…”

“…Micro‐neutralization antibodies prevent infection and therefore are a direct measure of protection, although HA stalk‐specific antibodies may also confer protection through neutralization or by ADCC through Fc–FcγR interactions . We have previously reported a slight trend of an increase in group 1 HA stalk‐specific IgG in children after LAIV, but not in adults . Stalk‐specific neutralizing antibodies also showed a slight boost after the first dose in children, suggesting that LAIV could be used as a priming vaccine for inducing broadly cross‐reactive stalk responses.…”

“…In our previous study, we found no increase in HI antibodies to the H1N1 strain after LAIV; however, most children had pre-existing antibodies. 28 However, a slight trend of rising H1N1 stalk-specific antibodies was observed in children after LAIV, whereas adults had already higher levels of H1-stalkspecific IgG antibodies prevaccination and no further increase was observed after vaccination. We suggested that this was due to pre-existing antibodies present after vaccination or infection during the 2009 pandemic.…”

“…Children received one (≥9 years old, n = 6) or two doses (<9 years old, n = 14) of LAIV in 2012 at a 4‐week interval, whereas adults received a single dose in 2013‐2014 season . Blood samples were collected at day 0 (prevaccination), 28 and 56 days post‐vaccination and plasma aliquoted and frozen for use in the serological assays, as previously described . In children, cell preparation tubes (CPT, BD) were used to separate peripheral blood mononuclear cells (PBMCs) for the ELISpot assay.…”

“…The MN assay was conducted as previously described. 28 Briefly, plasma and control sheep serum samples (NIBSC) were twofold serially diluted from 1:10 in flat-bottom 96well cell culture plates (Nunclon Delta Surface) before incubation with one hundred 50% tissue culture infectious does (TCID 50 )/50 µL/well of X-179A for 1 hour at room temperature. Then, 1.5 × 10 5 MDCK (Mardin-Darby Canine Kidney) cells/mL was added and incubated for 16-18 hours at 37°C.…”