Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse model
IntroductionYersinia pestis is the etiological agent of plague, a disease that remains a concern as demonstrated by recent outbreaks in Madagascar. Infection with Y. pestis results in a rapidly progressing illness that can only be successfully treated with antibiotics given shortly after symptom ons...
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2025-06-01
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| author | Sergei S. Biryukov Amy Rasley Amy Rasley Michael L. Davies Christopher P. Klimko Jennifer L. Dankmeyer Melissa Hunter Nathaniel O. Rill Jennifer L. Shoe Jeremy Miller Yuli Talyansky Barbara Sullinger Matheo Herrera Daniel Huang Leslie Bautista Lucy Pepe Sandra K. G. Peters Christian J. Xander Elsie E. Martinez Ronald G. Toothman Kevin D. Mlynek Joel A. Bozue Ju Qiu Nicholas O. Fischer Christopher K. Cote |
| author_facet | Sergei S. Biryukov Amy Rasley Amy Rasley Michael L. Davies Christopher P. Klimko Jennifer L. Dankmeyer Melissa Hunter Nathaniel O. Rill Jennifer L. Shoe Jeremy Miller Yuli Talyansky Barbara Sullinger Matheo Herrera Daniel Huang Leslie Bautista Lucy Pepe Sandra K. G. Peters Christian J. Xander Elsie E. Martinez Ronald G. Toothman Kevin D. Mlynek Joel A. Bozue Ju Qiu Nicholas O. Fischer Christopher K. Cote |
| author_sort | Sergei S. Biryukov |
| collection | DOAJ |
| description | IntroductionYersinia pestis is the etiological agent of plague, a disease that remains a concern as demonstrated by recent outbreaks in Madagascar. Infection with Y. pestis results in a rapidly progressing illness that can only be successfully treated with antibiotics given shortly after symptom onset. Live attenuated or whole cell inactivated vaccines confer protection against bubonic plague, but pneumonic plague has been more difficult to prevent. Novel effective subunit vaccine formulations may circumvent some of these shortfalls. Here, we compare the immunogenicity generated by an advanced subunit vaccine (F1V fusion protein) and a nanolipoprotein particle (NLP)-based vaccine.MethodsThe NLP, a high-density lipoprotein mimetic, provides a nanoscale delivery platform for recombinant Y. pestis antigens LcrV (V) and F1. BALB/c mice were immunized via subcutaneous injection twice, three or four weeks apart. Four weeks later, splenocytes and sera were collected for immune profiling, and mice were challenged with aerosolized Y. pestis CO92.ResultsBoth formulations induced a strong IgG response against the F1 and V proteins, along with a robust memory B cell response and a balanced cell-mediated immune response as evidenced by both Th1- and Th2-related cytokines. The NLP-based vaccine induced a stronger cytokine response against F1, V, and F1V proteins relative to the F1V vaccine. As with F1V, the inclusion of Alhydrogel (Alu) in NLP vaccine formulations was critical for enhanced immunogenicity and protective efficacy. Mice that received two doses of F1:V:NLP + Alu and CpG were completely protected from a challenge with approximately eight median lethal doses of aerosolized Y. pestis CO92 and this protection confirmed the well-documented synergy between the F1 and V antigens in context of pneumonic plague. The NLPs have defined regions of polarity that facilitates the incorporation of a wide range of adjuvants and antigens with distinct physicochemical properties and are an excellent candidate platform for the development of multi-antigen vaccines. |
| format | Article |
| id | doaj-art-bb9109d0c777464382b0ac1f3ebe8b4e |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-bb9109d0c777464382b0ac1f3ebe8b4e2025-08-20T03:24:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16037101603710Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse modelSergei S. Biryukov0Amy Rasley1Amy Rasley2Michael L. Davies3Christopher P. Klimko4Jennifer L. Dankmeyer5Melissa Hunter6Nathaniel O. Rill7Jennifer L. Shoe8Jeremy Miller9Yuli Talyansky10Barbara Sullinger11Matheo Herrera12Daniel Huang13Leslie Bautista14Lucy Pepe15Sandra K. G. Peters16Christian J. Xander17Elsie E. Martinez18Ronald G. Toothman19Kevin D. Mlynek20Joel A. Bozue21Ju Qiu22Nicholas O. Fischer23Christopher K. Cote24Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, United StatesDepartment of Molecular and Cell Biology, University of California, Merced, Merced, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesVaxcyte, Inc., San Carlos, CA, United StatesVaxcyte, Inc., San Carlos, CA, United StatesVaxcyte, Inc., San Carlos, CA, United StatesVaxcyte, Inc., San Carlos, CA, United StatesVaxcyte, Inc., San Carlos, CA, United StatesBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesRegulated Research Administration: Biostatistics Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesIntroductionYersinia pestis is the etiological agent of plague, a disease that remains a concern as demonstrated by recent outbreaks in Madagascar. Infection with Y. pestis results in a rapidly progressing illness that can only be successfully treated with antibiotics given shortly after symptom onset. Live attenuated or whole cell inactivated vaccines confer protection against bubonic plague, but pneumonic plague has been more difficult to prevent. Novel effective subunit vaccine formulations may circumvent some of these shortfalls. Here, we compare the immunogenicity generated by an advanced subunit vaccine (F1V fusion protein) and a nanolipoprotein particle (NLP)-based vaccine.MethodsThe NLP, a high-density lipoprotein mimetic, provides a nanoscale delivery platform for recombinant Y. pestis antigens LcrV (V) and F1. BALB/c mice were immunized via subcutaneous injection twice, three or four weeks apart. Four weeks later, splenocytes and sera were collected for immune profiling, and mice were challenged with aerosolized Y. pestis CO92.ResultsBoth formulations induced a strong IgG response against the F1 and V proteins, along with a robust memory B cell response and a balanced cell-mediated immune response as evidenced by both Th1- and Th2-related cytokines. The NLP-based vaccine induced a stronger cytokine response against F1, V, and F1V proteins relative to the F1V vaccine. As with F1V, the inclusion of Alhydrogel (Alu) in NLP vaccine formulations was critical for enhanced immunogenicity and protective efficacy. Mice that received two doses of F1:V:NLP + Alu and CpG were completely protected from a challenge with approximately eight median lethal doses of aerosolized Y. pestis CO92 and this protection confirmed the well-documented synergy between the F1 and V antigens in context of pneumonic plague. The NLPs have defined regions of polarity that facilitates the incorporation of a wide range of adjuvants and antigens with distinct physicochemical properties and are an excellent candidate platform for the development of multi-antigen vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1603710/fullplagueYersinia pestisvaccinenanolipoprotein particlemicepneumonic |
| spellingShingle | Sergei S. Biryukov Amy Rasley Amy Rasley Michael L. Davies Christopher P. Klimko Jennifer L. Dankmeyer Melissa Hunter Nathaniel O. Rill Jennifer L. Shoe Jeremy Miller Yuli Talyansky Barbara Sullinger Matheo Herrera Daniel Huang Leslie Bautista Lucy Pepe Sandra K. G. Peters Christian J. Xander Elsie E. Martinez Ronald G. Toothman Kevin D. Mlynek Joel A. Bozue Ju Qiu Nicholas O. Fischer Christopher K. Cote Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse model Frontiers in Immunology plague Yersinia pestis vaccine nanolipoprotein particle mice pneumonic |
| title | Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse model |
| title_full | Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse model |
| title_fullStr | Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse model |
| title_full_unstemmed | Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse model |
| title_short | Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse model |
| title_sort | nanolipoprotein particle nlp vaccine confers protection against yersinia pestis aerosol challenge in a balb c mouse model |
| topic | plague Yersinia pestis vaccine nanolipoprotein particle mice pneumonic |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1603710/full |
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