Adjuvant selection for optimally balanced humoral and cellular immunity induced by SARS-CoV-2 Spike virosome vaccines

Grobben, M.; Kerster, G.; Siteur-van Rijnstra, E.; Brinkkemper, M.; Poniman, M.; Burger, J. A.; Tejjani, K.; van Rijswijk, J.; Ait Addouch, W.; Oomen, M.; Bouhuijs, J. H.; Bijl, T.; Kempers, R.; Sliepen, K.; Stegmann, T.; van Gils, M. J.; Claireaux, M.; van der Velden, Y. U.; Sanders, R. W.

doi:10.64898/2026.06.23.733553

bioRxiv · 10.64898/2026.06.23.733553

Adjuvant selection for optimally balanced humoral and cellular immunity induced by SARS-CoV-2 Spike virosome vaccines

Grobben, M.·Kerster, G.·Siteur-van Rijnstra, E.·Brinkkemper, M.·Poniman, M.·Burger, J. A.·Tejjani, K.·van Rijswijk, J.·Ait Addouch, W.·Oomen, M.·Bouhuijs, J. H.·Bijl, T.·Kempers, R.·Sliepen, K.·Stegmann, T.·van Gils, M. J.·Claireaux, M.·van der Velden, Y. U.·Sanders, R. W.

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Abstract

Current SARS-CoV-2 vaccines provide limited breadth of protection, underscoring the need for vaccine strategies that optimize immune responses. Virosomesoffer a modular vaccine platform that enables multivalent antigen display and incorporation of adjuvants which can steer immune responses. We evaluated the immune response in BALB/c mice with virosomes displaying SARS-CoV-2 Wuhan or Delta spike antigens and coupled with various distinct adjuvants. Adjuvant selection differentially influenced both humoral and cellular immune outcomes. The TLR7/8 agonist 3M -052 induced a strong Th1-biased response, characterized by elevated IgG2a/IgG1 ratios and robust type 1 cytokine induction with suppression of Th2-associated cytokines. In contrast, the saponin QS-21 enhanced antibody functional quality, illustrated by improved virus neutralization potency and breadth. Furthermore, the combined incorporation of both 3M-052 and QS-21 induced an elevated Th1-biased response without improving neutralization capacity. In conclusion, different adjuvants added onto our virosome-basedvaccine led to distinct antibody responses and splenic T-cell profiles, reflective of differences in immune programming. This information guides the selection of adjuvants for respiratory virus vaccines.

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Grobben, M., Kerster, G., Siteur-van Rijnstra, E., Brinkkemper, M., Poniman, M., Burger, J. A., Tejjani, K., van Rijswijk, J., Ait Addouch, W., Oomen, M., Bouhuijs, J. H., Bijl, T., Kempers, R., Sliepen, K., Stegmann, T., van Gils, M. J., Claireaux, M., van der Velden, Y. U., Sanders, R. W.. 2026-06-24. Adjuvant selection for optimally balanced humoral and cellular immunity induced by SARS-CoV-2 Spike virosome vaccines. https://doi.org/10.64898/2026.06.23.733553

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