Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
Evaluation of the surface lipoprotein assembly modifier (Slam) as a vaccine candidate against Neisseria gonorrhoeae infection
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 12 April 2026

Evaluation of the surface lipoprotein assembly modifier (Slam) as a vaccine candidate against Neisseria gonorrhoeae infection

  • Ya He1,2,
  • Yu Huang3,
  • Feng Dong4,
  • Weiyuan Wang1,2,
  • Li Zhang1,2 &
  • …
  • Lei Zhang1,2 

Scientific Reports (2026) Cite this article

  • 1011 Accesses

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Immunology
  • Microbiology

Abstract

The surface lipoprotein assembly modifier (Slam) plays an essential role in the biogenesis and assembly of outer membrane components in Gram-negative bacteria. This study evaluated the potential of recombinant NG Slam as a vaccine candidate. Bioinformatics confirmed its high conservation (including with its Neisseria meningitidis homolog) and outer membrane localization. Immunofluorescence demonstrated antibody accessibility to Slam in fixed bacterial cells. Antigenic epitope mapping revealed that dominant B- and T-cell epitopes are primarily within α-helical and random coil regions. Molecular docking suggested potential interactions with Toll-like receptors TLR2 and TLR4, which warrant experimental validation. The recombinant protein corresponding to the C-terminal surface-exposed domain of Slam was successfully expressed and used to immunize BALB/c mice. Immunization elicited high titers of specific antibodies with potent complement-dependent serum bactericidal activity and significant inhibition of bacterial adhesion to epithelial cells. Furthermore, splenocyte proliferation and enhanced secretion of IL-4, IL-17 A, and IFN-γ were observed, with IL-17 A production markedly exceeding that induced by whole-cell antigens. These findings demonstrate that Slam is immunogenic and elicits functional antibody alongside a Th17-skewed cellular response, the protective relevance of which requires further evaluation in challenge models.

Similar content being viewed by others

SLAMF7 (CD319) on activated CD8+ T cells transduces environmental cues to initiate cytotoxic effector cell responses

Article Open access 10 October 2024

Identification and elucidation of cross talk between SLAM Family Member 7 (SLAMF7) and Toll-like receptor (TLR) pathways in monocytes and macrophages

Article Open access 07 July 2023

SLAMF7 defines subsets of human effector CD8 T cells

Article Open access 28 December 2024

Data availability

All data supporting the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Lin, E. Y., Adamson, P. C. & Klausner, J. D. Epidemiology treatments, and vaccine development for antimicrobial-resistant Neisseria gonorrhoeae: current strategies and future directions. Drugs 81, 1153–1169. https://doi.org/10.1007/s40265-021-01530-0 (2021).

  2. Williams, E. et al. Neisseria gonorrhoeae vaccines: a contemporary overview. Clin. Microbiol. Rev. 37, e0009423. https://doi.org/10.1128/cmr.00094-23 (2024).

    Google Scholar 

  3. Ohnishi, M. et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea? Detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob. Agents Chemother. 55, 3538–3545. https://doi.org/10.1128/aac.00325-11 (2011).

    Google Scholar 

  4. Serruto, D. et al. Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective immunity in humans. Proc. Natl. Acad. Sci. U S A. 107, 3770–3775. https://doi.org/10.1073/pnas.0915162107 (2010).

    Google Scholar 

  5. Cole, G. B., Bateman, T. J. & Moraes, T. F. The surface lipoproteins of gram-negative bacteria: protectors and foragers in harsh environments. J. Biol. Chem. 296, 100147. https://doi.org/10.1074/jbc.REV120.008745 (2021).

    Google Scholar 

  6. Hooda, Y. et al. Slam is an outer membrane protein that is required for the surface display of lipidated virulence factors in Neisseria. Nat. Microbiol. 1, 16009. https://doi.org/10.1038/nmicrobiol.2016.9 (2016).

    Google Scholar 

  7. Hooda, Y., Lai, C. C. L. & Moraes, T. F. Identification of a large family of Slam-dependent surface lipoproteins in gram-negative bacteria. Front. Cell. Infect. Microbiol. 7, 207. https://doi.org/10.3389/fcimb.2017.00207 (2017).

    Google Scholar 

  8. Yao, S. et al. NetGO 2.0: improving large-scale protein function prediction with massive sequence, text, domain, family and network information. Nucleic Acids Res. 49, W469–w475. https://doi.org/10.1093/nar/gkab398 (2021).

    Google Scholar 

  9. Yan, Z. et al. Next-generation IEDB tools: a platform for epitope prediction and analysis. Nucleic Acids Res. 52, W526–w532. https://doi.org/10.1093/nar/gkae407 (2024).

    Google Scholar 

  10. Yan, Y., Tao, H., He, J. & Huang, S. Y. The HDOCK server for integrated protein-protein docking. Nat. Protoc. 15, 1829–1852. https://doi.org/10.1038/s41596-020-0312-x (2020).

    Google Scholar 

  11. Lu, Q. et al. Intranasal trivalent candidate vaccine induces strong mucosal and systemic immune responses against Neisseria gonorrhoeae. Front. Immunol. 15, 1473193. https://doi.org/10.3389/fimmu.2024.1473193 (2024).

    Google Scholar 

  12. Lovett, A. & Duncan, J. A. Human immune responses and the natural history of Neisseria gonorrhoeae infection. Front. Immunol. 9, 3187. https://doi.org/10.3389/fimmu.2018.03187 (2018).

    Google Scholar 

  13. Quillin, S. J. & Seifert, H. S. Neisseria gonorrhoeae host adaptation and pathogenesis. Nat. Rev. Microbiol. 16, 226–240. https://doi.org/10.1038/nrmicro.2017.169 (2018).

    Google Scholar 

  14. Russell, M. W., Gray-Owen, S. D. & Jerse, A. E. Editorial: Immunity to Neisseria gonorrhoeae. Front. Immunol. 11, 1375. https://doi.org/10.3389/fimmu.2020.01375 (2020).

    Google Scholar 

  15. Kurt-Jones, E. A. et al. Interferon-epsilon, an estrogen-induced type I interferon, is uniquely exploited by Neisseria gonorrhoeae via effects on sialic acid metabolism. Cell. Host Microbe. 33, 1133–1145e1134. https://doi.org/10.1016/j.chom.2025.05.015 (2025).

    Google Scholar 

  16. Schubert-Unkmeir, A. & Christodoulides, M. Genome-based bacterial vaccines: current state and future outlook. BioDrugs 27, 419–430. https://doi.org/10.1007/s40259-013-0034-5 (2013).

    Google Scholar 

  17. Pizza, M. et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287, 1816–1820. https://doi.org/10.1126/science.287.5459.1816 (2000).

    Google Scholar 

  18. Velimirov, B. & Velimirov, B. A. Immune responses elicited by outer membrane vesicles of gram-negative bacteria: important players in vaccine development. Life (Basel). 14, 256. https://doi.org/10.3390/life14121584 (2024).

  19. Calvaresi, V. et al. Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA (2024).

  20. Tzeng, Y. L., Sannigrahi, S. & Stephens, D. S. NHBA antibodies elicited by 4CMenB vaccination are key for serum bactericidal activity against Neisseria gonorrhoeae. NPJ Vaccines. 9, 223. https://doi.org/10.1038/s41541-024-01018-4 (2024).

    Google Scholar 

  21. Feinen, B., Jerse, A. E., Gaffen, S. L. & Russell, M. W. Critical role of Th17 responses in a murine model of Neisseria gonorrhoeae genital infection. Mucosal Immunol. 3, 312–321. https://doi.org/10.1038/mi.2009.139 (2010).

    Google Scholar 

  22. Mills, K. H. G. IL-17 and IL-17-producing cells in protection versus pathology. Nat. Rev. Immunol. 23, 38–54. https://doi.org/10.1038/s41577-022-00746-9 (2023).

    Google Scholar 

  23. Liu, Y., Islam, E. A., Jarvis, G. A., Gray-Owen, S. D. & Russell, M. W. Neisseria gonorrhoeae selectively suppresses the development of Th1 and Th2 cells, and enhances Th17 cell responses, through TGF-β-dependent mechanisms. Mucosal Immunol. 5, 320–331. https://doi.org/10.1038/mi.2012.12 (2012).

    Google Scholar 

  24. Ruiz García, Y. et al. Urgent need to understand and prevent gonococcal infection: from the laboratory to real-world context. J. Infect. Dis. 230, e758–e767. https://doi.org/10.1093/infdis/jiae289 (2024).

    Google Scholar 

  25. Pedersen, G. K., Andersen, P. & Christensen, D. Immunocorrelates of CAF family adjuvants. Semin. Immunol. 39, 4–13. https://doi.org/10.1016/j.smim.2018.10.003 (2018).

    Google Scholar 

  26. Schick, J. et al. Cutting edge: TNF is essential for mycobacteria-induced MINCLE expression, macrophage activation, and Th17 adjuvanticity. J. Immunol. 205, 323–328. https://doi.org/10.4049/jimmunol.2000420 (2020).

    Google Scholar 

  27. Abraham, S. et al. Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Infect. Dis. 19, 1091–1100. https://doi.org/10.1016/s1473-3099(19)30279-8 (2019).

    Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81760303). The authors also thank the Institute of Pathogens and Vectors and the School of Basic Medicine at Dali University for providing research facilities and laboratory infrastructure.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81760303).

Author information

Authors and Affiliations

  1. Yunnan Provincial Key Laboratory of Technology for Prevention and Control of Natural Zoonotic Diseases, Institute of Pathogens and Vectors, Dali University, Dali, 671000, Yunnan, China

    Ya He, Weiyuan Wang, Li Zhang & Lei Zhang

  2. Comprehensive Laboratory of Pathogen Biology, School of Basic Medicine, Dali University, Dali, 671000, Yunnan, China

    Ya He, Weiyuan Wang, Li Zhang & Lei Zhang

  3. Junlian County Center for Traditional Chinese Medicine Development, Yibin, 645200, Sichuan, China

    Yu Huang

  4. Shandong Center for Disease Control and Prevention, Jinan, 250000, Shandong, China

    Feng Dong

Authors
  1. Ya He
    View author publications

    Search author on:PubMed Google Scholar

  2. Yu Huang
    View author publications

    Search author on:PubMed Google Scholar

  3. Feng Dong
    View author publications

    Search author on:PubMed Google Scholar

  4. Weiyuan Wang
    View author publications

    Search author on:PubMed Google Scholar

  5. Li Zhang
    View author publications

    Search author on:PubMed Google Scholar

  6. Lei Zhang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Ya He: Writing—original draft, methodology, conceptualization, data curation, validation, and formal analysis. Yu Huang: Methodology, Writing review, and editing. Feng Dong: Methodology, Resources. Weiyuan Wang: Methodology. **Li** Zhang: Writing review and editing, conceptualization, supervision. Lei Zhang: Writing review and editing, conceptualization, supervision, project administration, resources, and funding acquisition.

Corresponding authors

Correspondence to Li Zhang or Lei Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

This study was approved by the Animal Ethics Committee of Dali University (Approval No. 2024-PZ-028).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1 (download ZIP )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, Y., Huang, Y., Dong, F. et al. Evaluation of the surface lipoprotein assembly modifier (Slam) as a vaccine candidate against Neisseria gonorrhoeae infection. Sci Rep (2026). https://doi.org/10.1038/s41598-026-48171-5

Download citation

  • Received: 13 November 2025

  • Accepted: 06 April 2026

  • Published: 12 April 2026

  • DOI: https://doi.org/10.1038/s41598-026-48171-5

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Neisseria gonorrhoeae
  • Surface lipoprotein assembly modifier (SLAM)
  • Vaccine candidate
  • Immunogenicity
  • Immunoprotection
Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology