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Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination.

ABSTRACT: Influenza pandemics require rapid deployment of effective vaccines for control. Adjuvants such as AS03 improve vaccine immunogenicity, but this mechanism is poorly understood. We used high-throughput B cell receptor sequencing of plasma cells produced following AS03-adjuvanted and non-adjuvanted 2009 pandemic H1N1 vaccination, as well as pre-pandemic seasonal influenza vaccination to elucidate the effect of the adjuvant on the humoral immune response. By analyzing mutation levels, it was possible to distinguish sequences from cells that were recently activated from naïve B cells from those that were activated by memory recall. We show that the adjuvant functions through two mechanisms. First, the adjuvant stimulates increased activation of naïve B cells, thus reducing immune interference with previous vaccine responses. Second, the adjuvant is able to increase the adaptability of the recalled cells to give improved specificity to the new vaccine antigen. We thus show how AS03 enhances pH1N1 immune responses, and reduces immune interference.

SUBMITTER: Galson JD

PROVIDER: S-EPMC5110968 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination.

Galson J D JD Trück J J Kelly D F DF van der Most R R

Scientific reports 20161116

Influenza pandemics require rapid deployment of effective vaccines for control. Adjuvants such as AS03 improve vaccine immunogenicity, but this mechanism is poorly understood. We used high-throughput B cell receptor sequencing of plasma cells produced following AS03-adjuvanted and non-adjuvanted 2009 pandemic H1N1 vaccination, as well as pre-pandemic seasonal influenza vaccination to elucidate the effect of the adjuvant on the humoral immune response. By analyzing mutation levels, it was possibl ...[more]

PMID: 27849037

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Project description: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 ?g 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.

Dataset Information

Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination.

Publications

Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination.

Similar Datasets

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