About

Anna Wald is a Professor in the Department of Epidemiology at the University of Washington, with additional appointments in Medicine - Allergy and Infectious Diseases, and Laboratory Medicine and Pathology. Her research centers on the epidemiology and natural history of chronic viral infections in both immunocompetent and immunocompromised hosts. She is actively involved in clinical trials of antiviral therapeutics and prophylactic and therapeutic vaccines for viral pathogens. Her ongoing studies also address the interaction between sexually transmitted infections and the microbiome. Dr. Wald's work contributes to understanding viral infections and developing interventions to prevent and treat these diseases.

Research topics

• Medicine
• Immunology
• Environmental health
• Internal medicine
• Biology
• Genetics
• Obstetrics
• Gynecology
• Virology
• Computational biology
• Demography
• Family medicine

Selected publications

• Limitations of acyclovir and identification of potent HSV antivirals using 3D bioprinted human skin equivalents

  Nature Communications · 2025-10-16 · 4 citations

  articleOpen access

  Herpes simplex virus (HSV) infection poses global public health concerns with lifelong impacts. Acyclovir, the standard therapy, has limited efficacy in preventing subclinical shedding, and drug resistance occurs in immunocompromised patients, highlighting the need for novel therapeutics. Here we show that acyclovir is significantly less effective in skin-derived keratinocytes than donor-matched fibroblasts. Using 3D bioprinted human skin equivalents (HSEs) in a 96-well plate format, we have screened 738 compounds with broad targets and mechanisms of action, identifying potent antivirals, including 23 known or experimental HSV treatments. Unlike acyclovir, antivirals against HSV helicase/primase or host replication pathways display similar potency across cell types and donor sources in both 2D and 3D models. The reduced potency in keratinocytes may explain acyclovir's limited clinical efficacy. Our 3D bioprinted HSE assay platform enables the integration of patient-derived cells early in drug development and offers a physiologically relevant approach for HSV drug discovery.

  PublisherOA PDFDOI

• Anti-spike IgG4 and Fc effector responses: The impact of SARS-CoV-2 vaccine platform–specific priming and immune imprinting

  Journal of Infection · 2025-06-26 · 5 citations

  articleOpen access

  Proportional increases in anti-Spike (S) IgG4 associated with decreased Fc effector functions have been reported following repeated mRNA, but not recombinant protein-based (rS) (NVX-CoV2373, Novavax, Inc.), SARS-CoV-2 vaccination. We demonstrate the first evidence of a negative correlation between anti-S IgG4 and neutralizing antibody (nAb), as well as antibody-dependent surrogate Fc effector functions. Priming with two NVX-CoV2373 vaccines followed by a third dose was associated with higher IgG1 and IgG3, lower IgG4, higher nAb titers and surrogate Fc effector functions versus mRNA. Immune imprinting of anti-S IgG4 and nAbs, and Fc effector function imprinting after mRNA priming was observed. This effect was partially overcome by updated XBB.1.5 protein subunit vaccination, but not by ancestral vaccine strains. We establish correlation of anti-S IgG4 responses to reduced nAbs and surrogate Fc effector functions and demonstrate the impact of additional booster vaccination on subsequent immune response and Fc effector functions in the context of ancestral and XBB.1.5 strains.

  PublisherOA PDFDOI

• Anti-Spike IgG4 and Fc Effector Responses: The Impact of SARS-CoV-2 Vaccine Platform–Specific Priming and Immune Imprinting

  medRxiv · 2025-03-28

  preprintOpen access

  Abstract Proportional increases in anti-Spike (S) IgG4 associated with decreased Fc effector functions have been reported following repeated mRNA, but not recombinant protein-based (rS) (NVX-CoV2373, Novavax), SARS-CoV-2 vaccination. We demonstrate the first evidence of a negative correlation between anti-S IgG4 and neutralizing antibody (nAb) as well as antibody-dependent Fc effector functions. Priming with two NVX-CoV2373 vaccines followed by a third dose was associated with higher IgG1 and IgG3, lower IgG4, higher nAb titers and Fc effector functions versus mRNA. Immune imprinting of anti-S IgG4 and nAbs, and Fc effector function imprinting after mRNA priming was observed. This effect was partially overcome by updated XBB.1.5 protein subunit vaccination, but not ancestral vaccine strains. We establish correlation of anti-S IgG4 responses to reduced nAbs and Fc effector functions and demonstrate the impact of additional booster vaccination on subsequent immune response and Fc effector functions in the context of ancestral and XBB.1.5 strains.

  PublisherOA PDFDOI

• Herpes Simplex Virus Type 1 and Type 2 Western Blot Serology Test Results From 1999 to 2020 in a US Reference Laboratory

  Sexually Transmitted Diseases · 2025-12-11

  article

  We analyzed 162,397 deidentified HSV Western blot results performed at the University of Washington Virology Laboratory from 1999 to 2020. The seroprevalence of HSV-1 declined by 0.53% per year, whereas indeterminate HSV-1 results increased by 0.08% annually. Similarly, HSV-2 seroprevalence decreased by 0.72%, and indeterminate results increased by 0.16% each year.

  PublisherDOI

• Immunization with full-length TprC variants induces a broad response to surface-exposed epitopes of the Treponema pallidum repeat protein family and is partially protective in the rabbit model of syphilis

  Vaccine · 2025-06-25 · 3 citations

  articleOpen access

  An effective vaccine against syphilis could aid current control measures to reduce the incidence of infection. Protective immunity from the syphilis agent, Treponema pallidum subsp. pallidum ( T. pallidum ), is associated with pathogen clearance by phagocytosis, supporting that immunization with an effective vaccine candidate should elicit opsonic antibodies to key epitopes at the host-pathogen interface. The T . p allidum r epeat (Tpr) proteins are putative β-barrel outer membrane porins with ten predicted extracellular loops. Here, we immunized three groups of eight rabbits with either a combination of three recombinant variants of the full-length TprC antigen, the TprD 2 protein, or the conserved NH 2 -terminal region of TprK, with the latter antigen already known to induce incomplete protection in immunized rabbits. Compared to unimmunized controls, rabbits immunized with the three TprC variants or the TprK fragment exhibited attenuated primary chancres, reduced treponemal burden at the challenge sites, and limited pathogen dissemination to lymph nodes. Immunization with TprD 2 , alone did not produce comparable results. Strong humoral and cellular responses against TprC and TprK were elicited by immunization, and functional analyses supported the induction of opsonizing antibodies. Epitope mapping performed using TprC- and TprK-specific synthetic peptides and phage immunoprecipitation-sequencing identified a subset of highly reactive sequences and demonstrated immunity to predicted surface-exposed epitopes across multiple Tpr paralogs, which explained the significant, albeit incomplete protection measured post-challenge. These data advance TprC and TprK as syphilis vaccine candidates and highlight several correlates of their protection that deserve further examination.

  PublisherDOI

• Safety and immunogenicity of investigational herpes simplex virus-2 vaccines in adults with recurrent genital infection

  Vaccine · 2025-10-01

  article
  PublisherDOI

• Single cell methods allow phenotypic and clonotypic analysis of Treponema pallidum-specific CD4 T cells 4723

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description Syphilis is a major public health threat, but we have limited understanding of what constitutes protective immune responses in humans. Treponema pallidum (Tp)-specific CD4 T cell responses are likely important to heal syphilis lesions and are detectable and persistent in blood and in the skin rash of secondary syphilis. We sought to define the Tp-specific CD4 T cell phenotypes that may contribute to Tp clearance. After stimulating PBMC with Tp sonicate, individual Activation Induced Marker positive CD4 T cells were isolated and expanded as candidate Tp-specific T cell clones (TCC). From these TCC we obtained confirmation of pathogen specificity, paired TCRα/β sequences, and multiplexed cytokine analysis (IFNγ, IL10, IL13, IL17A, IL21, and IL5). We detected CD4 T cell responses to Tp from PBMC of participants with recently treated secondary syphilis, active early latent syphilis and remotely treated early latent syphilis. Initial TCR analysis from 53 of 136 Tp-reactive CD4 TCC revealed clusters of sequence-related TCRs suggesting an immunodominance hierarchy of clonotypes within individuals. We were further able to identify peptide epitopes for three TCC with unique TCR sequences. Functionally, most TCC were TH1-like with few examples of TH2, Treg, Tfh and rare TH17 phenotypes. We have defined Tp-specific CD4 phenotypes, refining our current understanding of CD4 T cell function during and after Tp infection, to inform vaccine design. Funding Sources Supported by NIH T32 AI07140, U19 AI144133, UM1 AI148684, K08 AI180375 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

  PublisherOA PDFDOI

• Stability of Spiked <i>Chlamydia Trachomatis</i> and <i>Neisseria Gonorrhea</i> in Urine and Swab Specimens After Prolonged Storage at Room and Freezer Temperatures Using Aptima Combo-2 Test

  Open Forum Infectious Diseases · 2025-06-30

  articleOpen access

  Abstract We evaluated whether prolonged storage at room and freezer temperatures affects detection of Chlamydia trachomatis and Neisseria gonorrhoeae (CT/GC) using Aptima Combo-2 assay for research studies. Three hundred specimens were spiked with CT/GC; half were stored at room temperature and half at −80°C. All specimens remained CT/GC positive for 36 months.

  PublisherOA PDFDOI

• Delayed Mortality Among Solid Organ Transplant Recipients Hospitalized for COVID-19

  UNC Libraries · 2025-04-18

  articleOpen access

  INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age &gt; 65 years [aHR 1.8 (1.3-2.4), p =&lt;0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p&lt;0.001] and body mass index &ge; 30&nbsp;kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, &gt;20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

  PublisherDOI

• Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infections in Immunocompromised Patients: Literature Review and Proposed Definitions for Use in Clinical Trials

  Clinical Infectious Diseases · 2025-01-29 · 8 citations

  article

  Herpes simplex virus (HSV) infection is one of the most prevalent viral infections worldwide. In general, host immunity is sufficient to clear viral shedding and recurrences, although it is insufficient to prevent subsequent virologic reactivations. In immunocompromised patients, prolonged and difficult-to-treat HSV infections may develop. The diagnosis of refractory HSV infection is based on the lack of clinical response to nucleoside analogs. Antiviral resistance is confirmed via genotypic and/or phenotypic testing. To provide consensus definitions of refractory and/or resistant (R/R) HSV mucocutaneous infections for clinical trial use, the HSV Resistance Working Group of the Transplant Associated Viral Infections Forum, which includes international clinicians, scientists, industry representatives, and regulatory officials, conducted a literature review of previously published data related to R/R HSV infections in immunocompromised patients. We propose definitions of R/R HSV mucocutaneous infections, which will be subject to re-evaluation and revision based on forthcoming data and future studies.

  PublisherDOI

Recent grants

• NIH Grant P01AI030731

  NIH · $64.0M · 2019

• NIH Grant P01AI03073125

  NIH · $5.1M · 2016

• NIH Grant U19AI113173

  NIH · $29.9M · 2020

• NIH Grant R21DA016066

  NIH · $453k · 2007

• NIH Grant K24AI07111306

  NIH · $183k · 2016

Frequent coauthors

• Lawrence Corey

  Fred Hutch Cancer Center

  978 shared

• Amalia Magaret

  University of Washington

  507 shared

• David M. Koelle

  University of Washington

  412 shared

• Christine Johnston

  Fred Hutch Cancer Center

  392 shared

• Stacy Selke

  University of Washington

  278 shared

• Meei‐Li Huang

  241 shared

• Keith R. Jerome

  University of Washington

  196 shared

• Corey Casper

  Fred Hutch Cancer Center

  190 shared

Labs

• Department of EpidemiologyPI