Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Adjuvant Activity of BCG Cell Wall Cytoskeleton on Dengue Virus-2 Subunit Vaccine

Version 1 : Received: 28 June 2023 / Approved: 29 June 2023 / Online: 29 June 2023 (09:46:48 CEST)

A peer-reviewed article of this Preprint also exists.

Jearanaiwitayakul, T.; Warit, S.; Lekjinda, K.; Seesen, M.; Limthongkul, J.; Midoeng, P.; Sunintaboon, P.; Ubol, S. The Adjuvant Activity of BCG Cell Wall Cytoskeleton on a Dengue Virus-2 Subunit Vaccine. Vaccines 2023, 11, 1344. Jearanaiwitayakul, T.; Warit, S.; Lekjinda, K.; Seesen, M.; Limthongkul, J.; Midoeng, P.; Sunintaboon, P.; Ubol, S. The Adjuvant Activity of BCG Cell Wall Cytoskeleton on a Dengue Virus-2 Subunit Vaccine. Vaccines 2023, 11, 1344.

Abstract

The uneven immunogenicity of the attenuated tetravalent dengue vaccine has created the diffi-culty to achieve a balanced protection against all four serotypes of dengue virus (DENV). To overcome this problem, non-replicative-based vaccines have come into focus as their immuno-genicity is adjustable. This approach is excellent for multivalent vaccines but commonly faces the issue of low immunogenicity. In this present study, we developed a non-replicating dengue vaccine composing of UV-inactivated dengue-2 virus (UV-DENV2) and DENV-2 NS1-279 protein encapsidated within nanoparticles. This vaccine candidate was administered in the presence of BCG cell wall cytoskeleton (BCG-CWS) as an adjuvant. We revealed, here, that encapsidated immunogens with BCG-CWS exerted potent activities on both B and T cells and elicited Th-1/Th-2 responses in mice. This was evidenced by strong neutralizing antibody activity with an unde-tectable antibody enhancing activity in a group of mice receiving encapsidated immunogens with BCG-CWS. Importantly, BCG-CWS significantly augmented antibody-mediated comple-ment-fixing activity, strongly stimulated the antigen-specific polyfunctional T cell responses as well as activated mixed Th-1/Th-2 responses specific to DENV2- and NS1-279 antigens. In conclu-sion, BCG-CWS potently adjuvanted the inactivated DENV-2 and subunit DENV immunogens. The mechanism of adjuvanticity remains unclear. This study revealed the potential use of BCG-CWS in vaccine development.

Keywords

Dengue nanovaccine; UV-inactivated dengue-2 virus; Non-structural protein 1; BCG cell wall cytoskeleton

Subject

Biology and Life Sciences, Virology

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