ORIGINAL RESEARCH article

Front. Immunol.

Sec. Microbial Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1598969

This article is part of the Research TopicTransforming Vaccine Strategies: Co-Delivery Systems for Robust Immunity and Disease ControlView all 5 articles

Novel Insights into ORFV B2L DNA Vaccine-Mediated Gut Microbiota Modulation and Immune Augmentation in Rats

Provisionally accepted
  • 1Huazhong Agricultural University, Wuhan, China
  • 2Xinjiang Academy of Animal Science, Ürümqi, Xinjiang Uyghur Region, China

The final, formatted version of the article will be published soon.

The Orf virus (ORFV) poses a significant threat to livestock and human health, causing economic losses in the livestock industry and potential zoonotic infections. Given the limitations of current vaccines, this study aimed to explore the immune response and gut microbiota modulation induced by ORFV B2L gene -based DNA vaccine (GV) and live -attenuated vaccine (LV) in rats, providing a basis for the development of more effective vaccines. Specific pathogen -free Sprague -Dawley female rats were divided into three groups: GV group, LV group, and control group. Rats in the GV group received intra-muscular injection of 100μg/dose of pVAX -B2L -asd plasmid, those in the LV group were immunized with a commercial live -attenuated vaccine, and the control group was injected with PBS. After immunization, various immune -related parameters, such as T -cell subsets, antibody levels, cytokines, and oxidative stress markers, were measured. The composition and function of gut microbiota were analyzed through 16S rRNA gene sequencing and PICRUSt -2 functional prediction. The GV group demonstrated enhanced cellular and humoral immunity. It had a higher percentage of CD4 + and CD8 + T cells, increased levels of IL -2, IL -6, and TNF -α cytokines, and elevated IgA and IgG antibody production compared to the LV and control groups. Additionally, the GV group showed reduced oxidative stress. In terms of gut microbiota, GV immunization led to an increase in beneficial bacteria like Lachnospi-raceae_NK4A136_group and a decrease in harmful or potentially pathogenic bacteria. KEGG pathway analysis indicated that differential flora were enriched in multiple metabolic pathways, including those related to biological systems, metabolism, and human diseases. In conclusion the ORFV B2L DNA vaccine (GV) induced a stronger immune response and had a positive impact on gut microbiota composition and function compared to the live -attenuated vaccine. These results suggest that the modulation of gut microbiota by the GV vaccine may play a crucial role in enhancing vaccine efficacy. This study provides new perspectives on ORFV vaccine development and the relationship between vaccines and gut microbiota.

Keywords: Orf virus, DNA vaccine, Gut Microbiota, immune response, vaccine development

Received: 24 Mar 2025; Accepted: 27 Jun 2025.

Copyright: © 2025 FAROOQ, Liu, Ahmed, Yang, Ahmed and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Xunping Jiang, Huazhong Agricultural University, Wuhan, China

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