Abstract
BackgroundNon‐neutralizing antibodies inducing complement‐dependent lysis (CDL) and antibody‐dependent cell‐mediated cytotoxicity (ADCC) activity may contribute to protection against influenza infection. We investigated CDL and ADCC responses in healthy adults randomized to receive either non‐adjuvanted or AS03‐adjuvanted monovalent A(H1N1)pdm09 vaccine (containing 15 µg/3.75 μg of hemagglutinin, respectively) on a 2‐dose schedule 21 days apart.MethodsWe conducted an exploratory analysis of a subset of 106 subjects having no prior history of A(H1N1)pdm09 infection or seasonal influenza vaccination enrolled in a previously reported study (NCT00985673). Antibody responses against the homologous A/California/7/2009 (H1N1) vaccine strain and a related A/Brisbane/59/2007 (H1N1) seasonal influenza strain were analyzed up to Day 42.ResultsBaseline seropositivity determined with hemagglutination inhibition (HI), CDL and ADCC antibody titers against viral strains was high; A/California/7/2009 (HI [40.4‐48.1%]; CDL [34.6‐36.0%]; ADCC [92.1‐92.3%]); A/Brisbane/59/2007 (HI [73.1‐88.9%]; CDL [38.0‐42.0%]; ADCC [86.8‐97.0%]). CDL seropositivity increased following vaccination with both adjuvanted and non‐adjuvanted formulations (A/California/7/2009 [95.9‐100%]; A/Brisbane/59/2007 [75.5‐79.6%]). At Day 21, increases in CDL and ADCC antibody geometric mean titers against both strains were observed for both formulations. After 2 doses of AS03‐adjuvanted vaccine, vaccine responses of 95.8% (≥9‐fold increase from baseline in CDL titers) and 34.3% (≥16‐fold increase from baseline in ADCC titers) were seen against A/California/7/2009; and 22.4% and 42.9%, respectively, against A/Brisbane/59/2007. Vaccine responses after 2 doses of the non‐adjuvanted vaccine were broadly similar.ConclusionsBroadly comparable non‐neutralizing immune responses were observed following vaccination with non‐adjuvanted and AS03‐adjuvanted A(H1N1)pdm09 formulations; including activity against a related vaccine strain.
Highlights
Following influenza virus infection, a robust immune response is observed involving the generation of both neutralizing and non-neutralizing antibodies.[1]
The role of complement-dependent lysis (CDL) and antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies in response to influenza infection or following vaccination is of considerable interest, with a number of reports in recent years.[7,9,13,15,16,17,18]
TA B L E 2 Complement-dependent lysis (CDL) and antibody-dependent cell-mediated cytotoxicity (ADCC) antibody responses to A/California/7/2009 and A/Brisbane/59/2007 strains
Summary
A robust immune response is observed involving the generation of both neutralizing and non-neutralizing antibodies.[1]. The aims were to characterize non-neutralizing antibody immunogenicity against the homologous A(H1N1)pdm[09] vaccine strain (A/California/7/2009) and against a related seasonal influenza strain; A/Brisbane/59/2007(H1N1) representative of a previously circulating seasonal H1N1 subtype (which in the context of the present analysis we consider this to be a heterologous vaccine strain)
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