Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS-21 induce strong humoral and cellular immune responses against hepatitis B surface antigen which persist for at least 4 years after vaccination

Leroux-Roels, Geert;Van Belle, Pascale;Vandepapeliere, Pierre;Horsmans, Yves;Van Mechelen, Marcelle;et.al.
(2015) Vaccine — Vol. 33, n° 8, p. 1084-1091 (2015)

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Authors
  • Leroux-Roels, Geert
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  • Van Belle, Pascale
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  • Vandepapeliere, Pierre
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  • Horsmans, YvesUCLouvain
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  • Van Mechelen, Marcelle
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Abstract
Background: Recombinant hepatitis B surface antigen (HBsAg) was used as a model antigen to evaluate persistence of cellular and humoral immune responses when formulated with three different Adjuvant Systems containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS-21, in an oil-in-water emulsion (AS02<inf>B</inf> and AS02<inf>V</inf>), or with liposomes (AS01<inf>B</inf>). Methods: This is an open, 4-year follow-up of a previous randomised, double-blind study. Healthy subjects aged 18-40 years received three vaccine doses on a month 0, 1, 10 schedule and were initially followed for 18 months. A total of 93 subjects (AS02<inf>B</inf>: n=30; AS02<inf>V</inf>: n=28; AS01<inf>B</inf>: n=35) were enrolled in this follow-up and had an additional blood sample taken at Year 4 (NCT02153320). The primary endpoint was the frequency of HBsAg-specific CD4<sup>+</sup> and CD8<sup>+</sup> T-cells expressing cytokines upon short-term in vitro stimulation of peripheral blood mononuclear cells with HBsAg-derived peptides. Secondary endpoints were anti-HBs antibody titres and frequency of HBsAg-specific memory B-cells. Results: A strong and persistent specific CD4<sup>+</sup> T-cell response was observed at Year 4 in all groups. HBsAg-specific CD4<sup>+</sup> T-cells expressed mainly CD40L and IL-2, and to a lesser extent TNF-α and IFN-γ. HBsAg-specific CD8<sup>+</sup> T-cells were not detected in any group. A high, persistent HBsAg-specific humoral immune response was observed in all groups, with all subjects seroprotected (antibody titre ≥10mIU/mL) at Year 4. The geometric mean antibody titre at Year 4 was above 100,000mIU/mL in all groups. A strong memory B-cell response was observed post-dose 2, which tended to increase post-dose 3 and persisted at Year 4 in all groups. Conclusion: The MPL/QS-21/HBsAg vaccine formulations induced persistent immune responses up to 4 years after first vaccination. These Adjuvant Systems offer potential for combination with recombinant, synthetic or highly purified subunit vaccines, particularly for vaccination against challenging diseases, or in specific populations, although additional studies are needed.
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Leroux-Roels, G., Van Belle, P., Vandepapeliere, P., Horsmans, Y., Janssens, M., Carletti, I., Garçon, N., Wettendorff, M., & Van Mechelen, M. (2015). Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS-21 induce strong humoral and cellular immune responses against hepatitis B surface antigen which persist for at least 4 years after vaccination. Vaccine, 33(8), 1084-1091. https://doi.org/10.1016/j.vaccine.2014.10.078 (Original work published 2015)