Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis

Abstract BB0405 is a surface exposed Borrelia burgdorferi protein and its vaccination protected mice against B. burgdorferi infection. As BB0405 is highly conserved across different B. burgdorferi sensu lato species, we investigated whether vaccination with recombinant BB0405 or through intradermal...

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Autores principales:	M. J. Klouwens, J. J. Trentelman, J. I. Ersoz, F. Nieves Marques Porto, R. Sima, O. Hajdusek, M. Thakur, U. Pal, J. W. Hovius
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77f0d1b506334ca0a0ffbfaa85022f00
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spelling	oai:doaj.org-article:77f0d1b506334ca0a0ffbfaa85022f002021-12-02T13:34:51ZInvestigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis10.1038/s41598-021-84130-y2045-2322https://doaj.org/article/77f0d1b506334ca0a0ffbfaa85022f002021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84130-yhttps://doaj.org/toc/2045-2322Abstract BB0405 is a surface exposed Borrelia burgdorferi protein and its vaccination protected mice against B. burgdorferi infection. As BB0405 is highly conserved across different B. burgdorferi sensu lato species, we investigated whether vaccination with recombinant BB0405 or through intradermal bb0405 DNA tattoo vaccination could provide protection against different Borrelia species, specifically against Borrelia afzelii, the predominant B. burgdorferi sensu lato genospecies causing Lyme borreliosis across Eurasia. We immunized C3H/HeN mice with recombinant BB0405 or with a codon-optimized bb0405 DNA vaccine using the pVAC plasmid and immunized corresponding control groups mice with only adjuvant or empty vectors. We subsequently subjected these immunized mice to a tick challenge with B. afzelii CB43-infected Ixodes ricinus nymphs. Upon vaccination, recombinant BB0405 induced a high total IgG response, but bb0405 DNA vaccination did not elicit antibody responses. Both vaccine formulations did not provide protection against Borrelia afzelii strain CB43 after tick challenge. In an attempt to understand the lack of protection of the recombinant vaccine, we determined expression of BB0405 and showed that B. afzelii CB43 spirochetes significantly and drastically downregulate the expression of BB0405 protein at 37 °C compared to 33 °C, where as in B. burgdorferi B31 spirochetes expression levels remain unaltered. Vaccination with recombinant BB0405 was previously shown to protect against B. burgdorferi sensu stricto. Here we show that vaccination with either recombinant BB0405 (or non-immunogenic bb0405 DNA), despite being highly conserved among B. burgdorferi sl genospecies, does not provide cross-protection against B. afzelii, mostly likely due to downregulation of this protein in B. afzelii in the mammalian host.M. J. KlouwensJ. J. TrentelmanJ. I. ErsozF. Nieves Marques PortoR. SimaO. HajdusekM. ThakurU. PalJ. W. HoviusNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M. J. Klouwens J. J. Trentelman J. I. Ersoz F. Nieves Marques Porto R. Sima O. Hajdusek M. Thakur U. Pal J. W. Hovius Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis
description	Abstract BB0405 is a surface exposed Borrelia burgdorferi protein and its vaccination protected mice against B. burgdorferi infection. As BB0405 is highly conserved across different B. burgdorferi sensu lato species, we investigated whether vaccination with recombinant BB0405 or through intradermal bb0405 DNA tattoo vaccination could provide protection against different Borrelia species, specifically against Borrelia afzelii, the predominant B. burgdorferi sensu lato genospecies causing Lyme borreliosis across Eurasia. We immunized C3H/HeN mice with recombinant BB0405 or with a codon-optimized bb0405 DNA vaccine using the pVAC plasmid and immunized corresponding control groups mice with only adjuvant or empty vectors. We subsequently subjected these immunized mice to a tick challenge with B. afzelii CB43-infected Ixodes ricinus nymphs. Upon vaccination, recombinant BB0405 induced a high total IgG response, but bb0405 DNA vaccination did not elicit antibody responses. Both vaccine formulations did not provide protection against Borrelia afzelii strain CB43 after tick challenge. In an attempt to understand the lack of protection of the recombinant vaccine, we determined expression of BB0405 and showed that B. afzelii CB43 spirochetes significantly and drastically downregulate the expression of BB0405 protein at 37 °C compared to 33 °C, where as in B. burgdorferi B31 spirochetes expression levels remain unaltered. Vaccination with recombinant BB0405 was previously shown to protect against B. burgdorferi sensu stricto. Here we show that vaccination with either recombinant BB0405 (or non-immunogenic bb0405 DNA), despite being highly conserved among B. burgdorferi sl genospecies, does not provide cross-protection against B. afzelii, mostly likely due to downregulation of this protein in B. afzelii in the mammalian host.
format	article
author	M. J. Klouwens J. J. Trentelman J. I. Ersoz F. Nieves Marques Porto R. Sima O. Hajdusek M. Thakur U. Pal J. W. Hovius
author_facet	M. J. Klouwens J. J. Trentelman J. I. Ersoz F. Nieves Marques Porto R. Sima O. Hajdusek M. Thakur U. Pal J. W. Hovius
author_sort	M. J. Klouwens
title	Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis
title_short	Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis
title_full	Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis
title_fullStr	Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis
title_full_unstemmed	Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis
title_sort	investigating bb0405 as a novel borrelia afzelii vaccination candidate in lyme borreliosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/77f0d1b506334ca0a0ffbfaa85022f00
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Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis

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