Non-neutralizing antibody responses following A(H1N1)pdm09 influenza vaccination with or without AS03 adjuvant system

Abstract

Background: Non-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.

Methods: We 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.

Results: Baseline 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.

Conclusions: Broadly 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.

Keywords: A(H1N1)pdm09 vaccine; AS03 adjuvant system; cross-reactivity; non-neutralizing antibodies.

Figure 1

Study flow. From the original according‐to‐protocol cohort from the primary study, 106 subjects were included: 52 receiving the non‐adjuvanted vaccine and 54 receiving the AS03‐adjuvanted vaccine. ADCC, antibody‐dependent cell‐mediated cytotoxicity; ATP, according‐to‐protocol; CDL, complement‐dependent lysis; HA, hemagglutinin; HI, hemagglutinin inhibition; n, number of subjects with available results for all three antibody responses (HI, CDL and ADCC); N, total number of subjects in the non‐adjuvanted or AS03‐adjuvanted vaccine group; TVC, total vaccinated cohort

Figure 2

Baseline seropositivity to hemagglutination inhibition (HI), complement‐dependent lysis (CDL), and antibody‐dependent cell‐mediated cytotoxicity (ADCC) antibodies against A/California/7/2009 and A/Brisbane/59/2007 strains at baseline (Day 0) and Day 42. D, Day

Figure 3

CDL and ADCC antibody geometric mean titers (GMTs) against A/California/7/2009 and A/Brisbane/59/2007 strains at baseline and Days 21 and 42. Upper panel represents GMTs as measured by CDL assay and lower panel by ADCC assay. ADCC, antibody‐dependent cell‐mediated cytotoxicity; CDL, complement‐dependent lysis; D, Day; GMT, geometric mean titer

Figure 4

Vaccine responses in subjects receiving non‐adjuvanted and AS03‐adjuvanted vaccines against A/California/7/2009 and A/Brisbane/59/2007 strains at Day 21 and Day 42. Presented here are higher vaccine response thresholds; defined as a 9‐fold increase from baseline (Day 0) at Day 21 or Day 42 for CDL antibodies (and as a 16‐fold increase for ADCC antibodies); see also data in Table S2. ADCC, antibody‐dependent cell‐mediated cytotoxicity; CDL, complement‐dependent lysis; D, Day