Suppressive effect of mycolactone-containing fraction from Mycobacterium ulcerans on antibody production against co-administered antigens

Shinoda, N.; Nakamura, Hajime; Watanabe, Mineo

doi:10.15761/brcp.1000126

Cited by 3 publications

(6 citation statements)

References 30 publications

(53 reference statements)

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“…The antibodies induced by the vaccine in this study may be functional but unable to access bacteria within the infection or it may be that multiple effector cell functions have been modulated by mycolactone exposure through interference with receptor expression on key innate immune cells, rendering these cells poorly responsive to antibodies. Suppression of protein-specific antibody production in the presence of mycolactone has been observed [66]. Mycolactone administered to a different location to the antigen caused no reduction to systemic antigen-specific IgG titres [66], similar to the observations from our study.…”

Section: Discussionsupporting

confidence: 90%

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High antibody titres induced by protein subunit vaccines against Buruli ulcer usingMycobacterium ulceransantigens Hsp18 and MUL_3720

Tobias

Marion

et al. 2020

Preprint

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24Background. Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue 25 infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study 26 was to investigate the vaccine potential of two previously described immunogenic M. 27 ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU. 28 Methods. Recombinant versions of the two proteins were each electrostatically coupled with a 29 previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were 30 vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged 31 with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-32 to-ulceration compared to unvaccinated mice. 33 Results. The MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies 34 that were predominately subtype IgG 1 . However, all mice developed ulcers by day-40 post-M. 35 ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration 36 between the experimental vaccine groups and unvaccinated animals.37

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Section: Discussionsupporting

confidence: 90%

“…Suppression of protein-specific antibody production in the presence of mycolactone has been observed [66]. Mycolactone administered to a different location to the antigen caused no reduction to systemic antigen-specific IgG titres [66], similar to the observations from our study.…”

Section: Discussionsupporting

confidence: 90%

High antibody titres induced by protein subunit vaccines against Buruli ulcer usingMycobacterium ulceransantigens Hsp18 and MUL_3720

Tobias

Marion

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The antibodies induced by the vaccine in this study may be functional but unable to access bacteria within the infection or it may be that multiple effector cell functions have been modulated by mycolactone exposure through interference with receptor expression on key innate immune cells, rendering these cells poorly responsive to antibodies. Suppression of protein-specific antibody production in the presence of mycolactone has been observed (Shinoda, Nakamura & Watanabe, 2017). Mycolactone administered to a different location than the antigen caused no reduction to systemic antigen-specific IgG titres (Shinoda, Nakamura & Watanabe, 2017), similar to the observations from our study.…”

Section: Discussionsupporting

confidence: 90%

High antibody titres induced by protein subunit vaccines usingMycobacterium ulceransantigens Hsp18 and MUL_3720 with a TLR-2 agonist fail to protect against Buruli ulcer in mice

Mangas

Tobias

Marion

et al. 2020

PeerJ

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Background Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously described immunogenic M. ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU. Methods Recombinant versions of the two proteins were each electrostatically coupled with a previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-to-ulceration compared to unvaccinated mice. Results The MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG1. However, all mice developed ulcers by day-40 post-M. ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration between the experimental vaccine groups and unvaccinated animals. Conclusions These data align with previous vaccine experiments using Hsp18 and MUL_3720 that indicated these proteins may not be appropriate vaccine antigens. This work highlights the need to explore alternative vaccine targets and different approaches to understand the role antibodies might play in controlling BU.

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“…The antibodies induced by the vaccine in this study may be functional but unable to access bacteria within the infection or it may be that multiple effector cell functions have been modulated by mycolactone exposure through interference with receptor expression on key innate immune cells, rendering these cells poorly responsive to antibodies. Suppression of protein-specific antibody production in the presence of mycolactone has been observed [75]. Mycolactone administered to a different location than the antigen caused no reduction to systemic antigen-specific IgG titres [75], similar to the observations from our study.…”

Section: Discussionsupporting

confidence: 90%

“…Suppression of protein-specific antibody production in the presence of mycolactone has been observed [75]. Mycolactone administered to a different location than the antigen caused no reduction to systemic antigen-specific IgG titres [75], similar to the observations from our study. Monoclonal antibodies against mycolactone have been shown to neutralize the cytotoxic activity of mycolactone in vitro indicating that mycolactone could be a viable vaccine target [76].…”

Section: Discussionsupporting

confidence: 90%

Peer Review #2 of "High antibody titres induced by protein subunit vaccines using Mycobacterium ulcerans antigens Hsp18 and MUL_3720 with a TLR-2 agonist fail to protect against Buruli ulcer in mice (v0.1)"

2020

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Background. Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously described immunogenic M. ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU. Methods. Recombinant versions of the two proteins were each electrostatically coupled with a previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-to-ulceration compared to unvaccinated mice. Results. The MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG 1. However, all mice developed ulcers by day-40 post-M. ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration between the experimental vaccine groups and unvaccinated animals. Conclusions. These data align with previous vaccine experiments using Hsp18 and MUL_3720 that indicated these proteins may not be appropriate vaccine antigens. This work highlights the need to explore alternative vaccine targets and different approaches to understand the role antibodies might play in controlling BU.

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Suppressive effect of mycolactone-containing fraction from Mycobacterium ulcerans on antibody production against co-administered antigens

Cited by 3 publications

References 30 publications

High antibody titres induced by protein subunit vaccines against Buruli ulcer usingMycobacterium ulceransantigens Hsp18 and MUL_3720

High antibody titres induced by protein subunit vaccines against Buruli ulcer usingMycobacterium ulceransantigens Hsp18 and MUL_3720

High antibody titres induced by protein subunit vaccines usingMycobacterium ulceransantigens Hsp18 and MUL_3720 with a TLR-2 agonist fail to protect against Buruli ulcer in mice

Peer Review #2 of "High antibody titres induced by protein subunit vaccines using Mycobacterium ulcerans antigens Hsp18 and MUL_3720 with a TLR-2 agonist fail to protect against Buruli ulcer in mice (v0.1)"

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