# Alexandra C. Walls

**Alexandra C. Walls** was lead author of the 2020 Cell paper defining the [SARS-CoV-2](https://www.edgepedia.org/sars-cov-2) spike structure<sup>[1](https://doi.org/10.1016/j.cell.2020.02.058)</sup> and of the 2021 and 2022 Cell papers on designed RBD-displaying nanoparticle vaccines and post-infection antibody responses.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9376299/)</sup> 

| Fact | Detail |
|---|---|
| Field | Structural biology of coronaviruses; protein and mRNA vaccine design |
| Doctoral training | PhD, University of Washington, 2019; advisor David Veesler |
| Signature work | "Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein", Cell, 2020 |
| Vaccine platform | Self-assembling I53-50 nanoparticle displaying 60 spike receptor-binding domains |
| Translation | GBP510; RBD-NP vaccine in phase I/II trials with CEPI phase III funding |
| Current role | Senior Scientist II, BioNTech US, from July 2024 |

## Education and career

Walls earned a [Bachelor of Science](https://www.edgepedia.org/bachelor-of-science) in [Biochemistry](https://www.edgepedia.org/biochemistry) and Molecular Biology at the [University of Massachusetts Amherst](https://www.edgepedia.org/university-of-massachusetts-amherst), then worked as a research technician in Biochemistry and Molecular Pharmacology at UMass Chan Medical School in Worcester.<sup>[5](https://orcid.org/0000-0002-9636-8330)</sup> She completed her PhD at the University of Washington in 2019 with a thesis titled "Understanding coronavirus fusion through structure", carried out in David Veesler's laboratory in the Department of Biochemistry.<sup>[6](http://hdl.handle.net/1773/45112)</sup><sup> • </sup><sup>[7](https://www.ipd.uw.edu/wp-content/uploads/2021/06/ScientificAmerican_Artificial-Proteins-Never-Seen-in-the-Natural-World-Are-Becoming-New-COVID-Vaccines-and-Medicines.pdf)</sup> Her doctorate was conferred in December 2019, and at her defense she warned that coronaviruses had pandemic potential and that the world was not prepared for such a pandemic.<sup>[7](https://www.ipd.uw.edu/wp-content/uploads/2021/06/ScientificAmerican_Artificial-Proteins-Never-Seen-in-the-Natural-World-Are-Becoming-New-COVID-Vaccines-and-Medicines.pdf)</sup>

She continued in the Veesler laboratory as a postdoctoral fellow; in February 2020 UW Medicine described her as a recent postdoctoral fellow and lead author of the preliminary bioRxiv report on the SARS-CoV-2 spike protein structure.<sup>[8](https://newsroom.uw.edu/news-releases/covid-19-coronavirus-spike-holds-infectivity-details)</sup> By October 2020 she was a research scientist in the Veesler laboratory.<sup>[2](https://newsroom.uw.edu/news-releases/ultrapotent-covid-19-vaccine-candidate-designed-computer)</sup> Her 2022 papers carry affiliations to the University of Washington Department of Biochemistry and to the [Howard Hughes Medical Institute](https://www.edgepedia.org/howard-hughes-medical-institute) at the University of Washington, which funds Veesler's laboratory.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9376299/)</sup> She moved to BioNTech US as Senior Scientist II in July 2024.<sup>[4](https://www.linkedin.com/in/alexandra-lexi-walls)</sup>

## Coronavirus spike structure and nanoparticle vaccines

Walls's pre-pandemic work concerned how coronavirus spike glycoproteins trigger membrane fusion, work she continued on SARS-CoV-2 from the first weeks of the outbreak.<sup>[6](http://hdl.handle.net/1773/45112)</sup><sup> • </sup><sup>[8](https://newsroom.uw.edu/news-releases/covid-19-coronavirus-spike-holds-infectivity-details)</sup> Her 2020 Cell paper on designed protein nanoparticle vaccines described self-assembling particles displaying 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array; in mice the particles induced neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose.<sup>[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7604136/)</sup> The platform is the computationally designed two-component complex [I53-50](https://www.edgepedia.org/i53-50), a 28 nm-wide, 120-subunit particle with icosahedral symmetry, with the RBD fused through glycine-serine linkers.<sup>[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7604136/)</sup> UW Medicine reported that the candidate had been transferred to two companies for clinical development.<sup>[2](https://newsroom.uw.edu/news-releases/ultrapotent-covid-19-vaccine-candidate-designed-computer)</sup>

Her 2021 Cell paper showed that a multivalent SARS-CoV-2 RBD nanoparticle vaccine protected mice from SARS-CoV-2 challenge after a single immunization, a potential dose-sparing strategy, and that mosaic and cocktail sarbecovirus RBD nanoparticles elicited broad neutralizing activity and protected against SARS-CoV challenge, providing proof of principle for heterotypic protection.<sup>[10](https://pubmed.ncbi.nlm.nih.gov/34619077/)</sup> Her 2022 Cell paper, "SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses" (volume 185, pages 872–880), showed that infection after vaccination produces neutralizing antibodies that are potent, broad, and durable.<sup>[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9376299/)</sup>

## Representative work

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (Cell, 2020) is the work that stands for her contribution: as lead author, with [David Veesler](https://www.edgepedia.org/david-veesler) as corresponding author, she reported in that paper the cryo-electron microscopy structure of the SARS-CoV-2 spike glycoprotein in the first months of the pandemic, defining the protein's architecture and antigenicity.<sup>[1](https://doi.org/10.1016/j.cell.2020.02.058)</sup><sup> • </sup><sup>[8](https://newsroom.uw.edu/news-releases/covid-19-coronavirus-spike-holds-infectivity-details)</sup> 

## Industry role and translation

Two lines of her work reached products. The RBD-NP vaccine from her 2021 paper was being evaluated in two phase I/II clinical trials (NCT04742738 and NCT04750343) and received funding from the Coalition for Epidemic Preparedness Innovations for phase III trials.<sup>[10](https://pubmed.ncbi.nlm.nih.gov/34619077/)</sup> The 2020 nanoparticle paper also launched cGMP manufacturing efforts to advance the vaccine into the clinic.<sup>[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7604136/)</sup> At BioNTech US she applies structural biology and immunology to next-generation mRNA therapeutics.<sup>[4](https://www.linkedin.com/in/alexandra-lexi-walls)</sup>

## How the approach compares with other broad-coronavirus vaccine designs

Several multivalent designs compete to broaden coronavirus protection, and they differ mainly in how they display antigens. The I53-50 platform fuses RBDs directly to a designed 120-subunit scaffold.<sup>[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC7604136/)</sup> A mosaic approach uses the SpyCatcher003-mi3 display platform to co-display four to eight distinct sarbecovirus RBDs on a 60-mer particle; in mice, mosaic nanoparticles elicited superior cross-reactive recognition of heterologous RBDs relative to homotypic SARS-CoV-2-RBD nanoparticles or COVID-19 convalescent human plasma.<sup>[11](https://www.science.org/doi/10.1126/science.abf6840)</sup> A ferritin-based mosaic vaccine co-displaying the RBDs of SARS-CoV, MERS-CoV, and SARS-CoV-2 induced robust cross-reactive neutralizing responses at a low 10 μg dose given at a 21-day interval and protected mice against challenge.<sup>[12](https://doi.org/10.1002/advs.202303366)</sup> A separate cocktail strategy mixes trivalent spike-protein nanoparticles (614D/SHC014/XBB) and completely protected human ACE2-transgenic hamsters against WIV1 and SHC014 challenge; a head-to-head study found no significant difference in neutralization titers between cocktail and mosaic spike-nanoparticle approaches.<sup>[13](https://preview-www.nature.com/articles/s41467-024-45495-6)</sup>

In previously vaccinated animals the picture is more constrained. A 2024 Cell study found that mosaic-8b nanoparticles, presenting eight sarbecovirus RBDs, elicited the greatest cross-reactivity in COVID-19-vaccinated non-human primates and mice compared with admixed or homotypic immunizations, and predominantly induced de novo antibodies against variant RBDs.<sup>[14](https://www.cell.com/cell/fulltext/S0092-8674(24)00846-8)</sup>

## Recent developments

Walls moved from academic coronavirus structural biology into industrial mRNA vaccine design, joining BioNTech US in July 2024.<sup>[4](https://www.linkedin.com/in/alexandra-lexi-walls)</sup> Her 2025 [Science Translational Medicine](https://www.edgepedia.org/science-translational-medicine) paper, "Computationally designed mRNA-launched protein nanoparticle immunogens elicit protective antibody and T cell responses in mice", combines the two lines of work, using mRNA to launch designed protein nanoparticle immunogens.<sup>[5](https://orcid.org/0000-0002-9636-8330)</sup> A 2026 bioRxiv paper, "Comprehensive Profiling of Monkeypox Virus Antigens Identifies Potent Targets for Next-Generation mRNA Vaccine Development", extends her antigen-selection work to monkeypox virus.<sup>[5](https://orcid.org/0000-0002-9636-8330)</sup>

## References

1. [Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (Cell, 2020)](https://doi.org/10.1016/j.cell.2020.02.058)
2. [Ultrapotent COVID-19 vaccine candidate designed via computer, UW Medicine Newsroom (2020)](https://newsroom.uw.edu/news-releases/ultrapotent-covid-19-vaccine-candidate-designed-computer)
3. [Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice (Cell Reports, 2022; its reference list documents Walls's lead authorship of the Cell 2021 and 2022 papers)](https://pmc.ncbi.nlm.nih.gov/articles/PMC9376299/)
4. [Lexi Walls, professional profile](https://www.linkedin.com/in/alexandra-lexi-walls)
5. [Alexandra Walls, ORCID 0000-0002-9636-8330](https://orcid.org/0000-0002-9636-8330)
6. [Understanding coronavirus fusion through structure, University of Washington dissertation (2019)](http://hdl.handle.net/1773/45112)
7. [Artificial Proteins Never Seen in the Natural World Are Becoming New COVID Vaccines and Medicines, Scientific American (hosted by UW Institute for Protein Design)](https://www.ipd.uw.edu/wp-content/uploads/2021/06/ScientificAmerican_Artificial-Proteins-Never-Seen-in-the-Natural-World-Are-Becoming-New-COVID-Vaccines-and-Medicines.pdf)
8. [COVID-19 coronavirus spike holds infectivity details, UW Medicine Newsroom (2020)](https://newsroom.uw.edu/news-releases/covid-19-coronavirus-spike-holds-infectivity-details)
9. [Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (Cell, 2020; PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC7604136/)
10. [Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines (Cell, 2021)](https://pubmed.ncbi.nlm.nih.gov/34619077/)
11. [Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice (Science, 2021)](https://www.science.org/doi/10.1126/science.abf6840)
12. [Mosaic RBD Nanoparticles Elicit Protective Immunity Against Multiple Human Coronaviruses in Animal Models (Advanced Science)](https://doi.org/10.1002/advs.202303366)
13. [Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine (Nature Communications, 2024)](https://preview-www.nature.com/articles/s41467-024-45495-6)
14. https://www.cell.com/cell/fulltext/S0092-8674(24)00846-8

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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in immunology, microbiology, and virology › Virology*

*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 11, 2026; Oct 15, 2026 · Last review: Sep 25, 2026*

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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license
