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Various Adjuvants Effect on Immunogenicity of Puumala Virus Vaccine.

ABSTRACT: Various adjuvant effects on the immunogenicity of the candidate inactivated Puumala virus vaccine were detected in BALB/c mice. Adjuvants under study were: aluminum hydroxide, spherical particles of Tobacco mosaic virus coat protein, B subunit of heat-labile enterotoxin of Escherichia coli, and low endotoxic lipopolysaccharide of Shigella sonnei. Aluminum hydroxide (1 mg/ml) did not affect neutralizing antibodies' induction and vaccine stability during storage compared to immunization with the vaccine without adjuvant. B subunit of heat-labile enterotoxin (0.2 µg/ml), low endotoxic lipopolysaccharide (50 µg/ml), and plant virus-based spherical particles (300 µg/ml) significantly enhance the humoral immune response of vaccine (p < 0.0001). Pronounced stimulation of IL-12 and IFN-? was observed when mice were immunized with vaccines both with adjuvants (except of aluminum hydroxide) and without adjuvants. It has been shown that low endotoxic lipopolysaccharide contributes not only to enhance the immune response but also to stabilize vaccine immunogenicity during at least 1 year storage.

SUBMITTER: Kurashova SS

PROVIDER: S-EPMC7649337 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Various Adjuvants Effect on Immunogenicity of Puumala Virus Vaccine.

Kurashova Svetlana S SS Ishmukhametov Aidar A AA Dzagurova Tamara K TK Egorova Maria S MS Balovneva Maria V MV Nikitin Nikolai A NA Evtushenko Ekaterina A EA Karpova Olga V OV Markina Anna A AA Aparin Peter G PG Tkachenko Petr E PE L Vov Vyatcheslav L VL Tkachenko Evgeniy A EA

Frontiers in cellular and infection microbiology 20201026

Various adjuvant effects on the immunogenicity of the candidate inactivated Puumala virus vaccine were detected in BALB/c mice. Adjuvants under study were: aluminum hydroxide, spherical particles of Tobacco mosaic virus coat protein, B subunit of heat-labile enterotoxin of <i>Escherichia coli</i>, and low endotoxic lipopolysaccharide of <i>Shigella sonnei</i>. Aluminum hydroxide (1 mg/ml) did not affect neutralizing antibodies' induction and vaccine stability during storage compared to immunizat ...[more]

PMID: 33194793

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Project description:Vaccine adjuvants enhance and prolong pathogen-specific protective immune responses. Recent reports indicate that host factors-such as aging, pregnancy, and genetic polymorphisms-influence efficacies of vaccines adjuvanted with Toll-like receptor (TLR) or known pattern-recognition receptor (PRR) agonists. Although PRR independent adjuvants (e.g., oil-in-water emulsion and saponin) are emerging, these adjuvants induce some local and systemic reactogenicity. Hence, new TLR and PRR-independent adjuvants that provide greater potency alone or in combination without compromising safety are highly desired. Previous cell-based high-throughput screenings yielded a small molecule 81 [N-(4-chloro-2,5-dimethoxyphenyl)-4-ethoxybenzenesulfonamide], which enhanced lipopolysaccharide-induced NF-κB and type I interferon signaling in reporter assays. Here compound 81 activated innate immunity in primary human peripheral blood mononuclear cells and murine bone marrow-derived dendritic cells (BMDCs). The innate immune activation by 81 was independent of TLRs and other PRRs and was significantly reduced in mitochondrial antiviral-signaling protein (MAVS)-deficient BMDCs. Compound 81 activities were mediated by mitochondrial dysfunction as mitophagy inducers and a mitochondria specific antioxidant significantly inhibited cytokine induction by 81. Both compound 81 and a derivative obtained via structure-activity relationship studies, 2F52 [N-benzyl-N-(4-chloro-2,5-dimethoxyphenyl)-4-ethoxybenzenesulfonamide] modestly increased mitochondrial reactive oxygen species and induced the aggregation of MAVS. Neither 81 nor 2F52 injected as adjuvants caused local or systemic toxicity in mice at effective concentrations for vaccination. Furthermore, vaccination with inactivated influenza virus adjuvanted with 2F52 demonstrated protective effects in a murine lethal virus challenge study. As an unconventional and safe adjuvant that does not require known PRRs, compound 2F52 could be a useful addition to vaccines.

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Various Adjuvants Effect on Immunogenicity of Puumala Virus Vaccine.

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Various Adjuvants Effect on Immunogenicity of Puumala Virus Vaccine.

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