Evaluating α-galactosylceramide as an adjuvant for live attenuated influenza vaccines in pigs.

Autor: Artiaga BL; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., Morozov I; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., Ransburgh R; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., Kwon T; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., Balaraman V; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., Indran SV; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., De Carvalho Madrid DM; Division of Animal Sciences, University of Missouri, Columbia, MO 65211 USA., Gu W; Department of Animal Sciences, University of Florida, Gainesville, FL 32611 USA., Henningson J; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., Ma W; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., Richt JA; Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506 USA., Driver JP; Division of Animal Sciences, University of Missouri, Columbia, MO 65211 USA.
Jazyk: angličtina
Zdroj: Animal diseases [Anim Dis] 2022; Vol. 2 (1), pp. 19. Date of Electronic Publication: 2022 Aug 01.
DOI: 10.1186/s44149-022-00051-x
Abstrakt: Natural killer T (NKT) cells activated with the glycolipid ligand α-galactosylceramide (α-GalCer) stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses. Several studies have used this approach to adjuvant inactivated and subunit influenza A virus (IAV) vaccines, including to enhance cross-protective influenza immunity. However, less is known about whether α-GalCer can enhance live attenuated influenza virus (LAIV) vaccines, which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating influenza vaccines. The current study used the swine influenza challenge model to assess whether α-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine (TX98ΔNS1) encoding a truncated NS1 protein. In one study, weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0, 10, 50, and 100 μg/kg doses of α-GalCer, and subsequently challenged with a heterologous H3N2 virus. All treatment groups were protected from infection. However, the addition of α-GalCer appeared to suppress nasal shedding of the LAIV vaccine. In another experiment, pigs vaccinated with the H3N2 LAIV, with or without 50 μg/kg of α-GalCer, were challenged with the heterosubtypic pandemic H1N1 virus. Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways, and significantly decreased virus shedding. On the other hand, combining the vaccine with α-GalCer reduced cross-protective cellular and antibody responses, and resulted in higher virus titers in respiratory tissues. These findings suggest that: (i) high doses of α-GalCer impair the replication and nasal shedding of the LAIV vaccine; and (ii) α-GalCer might interfere with heterosubtypic cross-protective immune responses. This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines.
Supplementary Information: The online version contains supplementary material available at 10.1186/s44149-022-00051-x.
Competing Interests: Competing interestsThe authors declare no conflict of interest in the present study. The funding sources had no part in study design and conceptualization, collection, analysis, or interpretation of data, writing the manuscript, or in the decision to publish results. The JAR laboratory received support from Tonix Pharmaceuticals, Genus plc, Xing Technologies and Zoetis, outside of the reported work. JAR is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections, owned by Kansas State University, KS. Author Jürgen A. Richt was not involved in the journal’s review or decisions related to this manuscript.
(© The Author(s) 2022.)
Databáze: MEDLINE
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