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<p>This study was conducted to develop a robust, scalable manufacturing process for the candidate vaccine r<i>Bm</i>HAXT for human lymphatic filariasis (LF). During scale-up production, r<i>Bm</i>HAXT showed significant antigen aggregation leading to a loss of purified vaccine antigens. This project aims to create an improved formulation suitable for industrial-scale production while maintaining robust protection. We generated three variants: (1) ∆Cys, in which all cysteinyl residues were mutated to serinyl. (2) GS, which has a flexible glycine-serine linker inserted between each of the component antigens, and (3) GS/∆Cys, a third variant with a combination of both the cysteine deletion and the addition of linkers. We then evaluated the immunogenicity and efficacy of each variant in a mouse model. We demonstrated that the ΔCys mutant retained immunogenicity and vaccine efficacy of the parent tag-free r<i>Bm</i>HAXT protein. We also performed an accelerated stability study. All preparations remained stable at 4°C, and the ΔCys variant remained stable even at 25°C throughout the study (6 weeks). The ∆Cys protein was stable with equivalent potency in mice. Therefore, ∆Cys is an optimal candidate for progression to cGMP (Current Good Manufacturing Practices) manufacturing and human clinical trials as a vaccine for lymphatic filariasis.</p>

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A next-generation human lymphatic filariasis vaccine candidate, rBmHAXT, for clinical development

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Nithila Saravanan,
  • Sean A. Gray,
  • Jennifer Davis,
  • Conrad M. Puff-Carter,
  • Jiho Kim,
  • Vishal Khatri,
  • Nikhil Chauhan,
  • Darrick Carter,
  • Ramaswamy Kalyanasundaram

摘要

This study was conducted to develop a robust, scalable manufacturing process for the candidate vaccine rBmHAXT for human lymphatic filariasis (LF). During scale-up production, rBmHAXT showed significant antigen aggregation leading to a loss of purified vaccine antigens. This project aims to create an improved formulation suitable for industrial-scale production while maintaining robust protection. We generated three variants: (1) ∆Cys, in which all cysteinyl residues were mutated to serinyl. (2) GS, which has a flexible glycine-serine linker inserted between each of the component antigens, and (3) GS/∆Cys, a third variant with a combination of both the cysteine deletion and the addition of linkers. We then evaluated the immunogenicity and efficacy of each variant in a mouse model. We demonstrated that the ΔCys mutant retained immunogenicity and vaccine efficacy of the parent tag-free rBmHAXT protein. We also performed an accelerated stability study. All preparations remained stable at 4°C, and the ΔCys variant remained stable even at 25°C throughout the study (6 weeks). The ∆Cys protein was stable with equivalent potency in mice. Therefore, ∆Cys is an optimal candidate for progression to cGMP (Current Good Manufacturing Practices) manufacturing and human clinical trials as a vaccine for lymphatic filariasis.