Characterization of Bacillus anthracis Spore Proteins Using a Nanoscaffold Vaccine Platform

Weilhammer, Dina R.; Dunkle, Alexis D.; Boone, Tyler; Gilmore, Sean F.; Khemmani, Mark; Peters, Sandra K. G.; Hoeprich, Paul D.; Fischer, Nicholas O.; Blanchette, Craig D.; Driks, Adam; Rasley, Amy

doi:10.3389/fimmu.2020.01264

Characterization of Bacillus anthracis Spore Proteins Using a Nanoscaffold Vaccine Platform

Journal Article · Tue Jun 23 00:00:00 EDT 2020 · Frontiers in Immunology

DOI:https://doi.org/10.3389/fimmu.2020.01264· OSTI ID:1755846

Weilhammer, Dina R. ^[1]; Dunkle, Alexis D. ^[2]; Boone, Tyler ^[3]; Gilmore, Sean F. ^[1]; Khemmani, Mark ^[3]; Peters, Sandra K. G. ^[1]; Hoeprich, Paul D. ^[1]; Fischer, Nicholas O. ^[1]; Blanchette, Craig D. ^[4]; Driks, Adam ^[3]; Rasley, Amy ^[1]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Genetech Inc., South San Francisco, CA (United States)
Loyola Univ. Medical Center, Chicago, IL (United States)
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Genentech Inc., South San Francisco, CA (United States)

Subunit vaccines are theoretically safe and easy to manufacture but require effective adjuvants and delivery systems to yield protective immunity, particularly at critical mucosal sites such as the lung. We investigated nanolipoprotein particles (NLPs) containing the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA) as a platform for intranasal vaccination against Bacillus anthracis. Modified lipids enabled attachment of disparate spore and toxin protein antigens. Intranasal vaccination of mice with B. anthracis antigen-MPLA-NLP constructs induced robust IgG and IgA responses in serum and in bronchoalveolar and nasal lavage. Typically, a single dose sufficed to induce sustained antibody titers over time. When multiple immunizations were required for sustained titers, specific antibodies were detected earlier in the boost schedule with MPLA-NLP-mediated delivery than with free MPLA. Administering combinations of constructs induced responses to multiple antigens, indicating potential for a multivalent vaccine preparation. No off-target responses to the NLP scaffold protein were detected. In summary, the NLP platform enhances humoral and mucosal responses to intranasal immunization, indicating promise for NLPs as a flexible, robust vaccine platform against B. anthracis and potentially other inhalational pathogens.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program; National Institutes of Health (NIH)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1755846

Report Number(s):: LLNL-JRNL--804100; 1007226

Journal Information:: Frontiers in Immunology, Journal Name: Frontiers in Immunology Vol. 11; ISSN 1664-3224

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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spore antigens
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Characterization of Bacillus anthracis Spore Proteins Using a Nanoscaffold Vaccine Platform

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