Robust Bioconjugated Antigens Induce Immune Responses Preventing Malaria Infection and its Transmission

Small, vol. 22, pp. e08762

Abstract

Malaria remains a major global health challenge, with current vaccines providing only limited reductions in case numbers. This study introduces an innovative approach that utilizes engineered Escherichia coli to bioconjugate and assemble the pre-erythrocytic circumsporozoite protein-derived RTS,S antigen and the sexual-stage Pfs47 subdomain into biopolymer particles (BPs), generating the dual-antigen Pfs47-RTS,S-BP vaccine. Compared to single-antigen BPs, the fused Pfs47-RTS,S-BP formulation shows synergistic enhancement in immunogenicity and protective efficacy. Pfs47‑RTS,S‑BP retains its physical properties and antigenicity after storage at 37°C. Although functional in vivo assessment of these thermostable formulations has not yet been performed, the findings indicate promising thermostability that could help overcome cold‑chain limitations in malaria‑endemic regions. Pfs47-RTS,S-BP induces durable antibody and T cell responses alongside crucial liver-resident memory T cells for frontline defence. Vaccine-induced antibodies efficiently neutralize sporozoites and inhibit parasite transmission. Pfs47-RTS,S-BP generates RTS,S-specific antibody levels 5.3-fold higher than the protective thresholds of the current RTS,S/AS01 vaccine. The Pfs47-RTS,S-BP formulation also achieves 80.4% protection against mosquito bite challenge and 68.15% transmission-reducing activity, demonstrating strong potential as a robust, dual-stage malaria vaccine candidate. Overall, this work underscores the potential of Pfs47‑RTS, S‑BP to overcome key limitations of current vaccines and to substantially advance global malaria control efforts.

Authors 11

1. Nivethika Sivakumaran

   Griffith University

   Affiliation as printed

   Centre For Cell Factories and Biopolymers Institute For Biomedicine and Glycomics Griffith University Nathan Australia

2. Yevel Flores-García

   Johns Hopkins University

   Affiliation as printed

   Johns Hopkins Malaria Research Institute Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

   W. Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

3. Chanel Milène Naar Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Interventional Molecular Imaging Laboratory Leiden University Medical Center Leiden The Netherlands

   Leiden University Center For Infectious Diseases (LUCID) Leiden University Medical Center Leiden The Netherlands

4. Shuxiong Chen

   Griffith University

   Affiliation as printed

   Centre For Cell Factories and Biopolymers Institute For Biomedicine and Glycomics Griffith University Nathan Australia

5. Mili Mehta

   Johns Hopkins University

   Affiliation as printed

   Johns Hopkins Malaria Research Institute Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

   W. Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

6. Fijs W. B. van Leeuwen Aachen

   Leiden University Medical Center

   Affiliation as printed

   Interventional Molecular Imaging Laboratory Leiden University Medical Center Leiden The Netherlands

7. Abhai Tripathi

   Johns Hopkins University

   Affiliation as printed

   Johns Hopkins Malaria Research Institute Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

   W. Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

8. Rajagopal Murugan Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center For Infectious Diseases (LUCID) Leiden University Medical Center Leiden The Netherlands

9. Meta Roestenberg Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center For Infectious Diseases (LUCID) Leiden University Medical Center Leiden The Netherlands

10. Fidel P. Zavala

    Johns Hopkins University

    Affiliation as printed

    Johns Hopkins Malaria Research Institute Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

    W. Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Johns Hopkins University Baltimore Maryland USA

11. Bernd H. A. Rehm corresponding

    Griffith University

    Affiliation as printed

    Centre For Cell Factories and Biopolymers Institute For Biomedicine and Glycomics Griffith University Nathan Australia