Christine Johnston

University of Washington Seattle | UW · Division of Allergy and Infectious Diseases

Background In the United States, booster vaccines for persons 18 years and older were approved under Emergency Use Authorization (EUA) in September 2021. Waning immunity following SARS-CoV-2 primary vaccination series led to recommendations for booster vaccination. Emerging data suggest that providing boosters different from the primary series (het...

Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells...

Importance Herpes simplex virus type 1 (HSV-1) is the leading cause of first-episode genital herpes in many countries. Objective To inform counseling messages regarding genital HSV-1 transmission, oral and genital viral shedding patterns among persons with first-episode genital HSV-1 infection were assessed. The trajectory of the development of HS...

Background Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies hav...

Two randomized controlled trials demonstrated no clinical benefit of hydroxychloroquine (HCQ) for either post‐exposure prophylaxis (PEP) or early treatment of SARS‐CoV‐2 infection. Using data from these studies, we calculated time‐weighted average change from baseline SARS‐CoV‐2 viral load and demonstrated that HCQ did not affect viral clearance. T...

The Omicron variant of SARS-CoV-2 exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations subs...

Herpes simplex virus (HSV) causes chronic infection in the human host, characterized by self-limited episodes of mucosal shedding and lesional disease, with latent infection of neuronal ganglia. The epidemiology of genital herpes has undergone a significant transformation over the past two decades, with the emergence of HSV-1 as a leading cause of...

Antigen-specific T RM persist and protect against skin or female reproductive tract (FRT) HSV infection. As the pathogenesis of HSV differs between humans and model organisms, we focus on humans with well-characterized recurrent genital HSV-2 infection. Human CD8+ T RM persisting at sites of healed human HSV-2 lesions have an activated phenotype bu...

Importance: Racial and ethnic diversity among study participants is associated with improved generalizability of clinical trial results and may address inequities in evidence that informs public health strategies. Novel strategies are needed for equitable access and recruitment of diverse clinical trial populations. Objective: To investigate dem...

COVID-19 symptom definitions rarely include symptom severity. We collected daily nasal swabs and symptom diaries from contacts of SARS-CoV-2 cases. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (CI: 52.9−66.7%) to 31.5% (CI: 25.7−38.0%), but increased specificity from 77.5% (CI:75.3−79.5%) to...

While detection of SARS-CoV-2 by diagnostic RT-PCR is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNA) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RT-PCR and sgRNA detection from nasal swabs collected daily by participants in post exposu...

The skin at the site of HSV-2 reactivation is enriched for HSV-2 specific T cells. To evaluate whether an immunotherapeutic vaccine could elicit skin-based memory T cells we studied skin biopsies and HSV-2-reactive CD4+ T cells from peripheral blood mononuclear cells (PBMCs) by T-cell receptor (TCR) sequencing before and after vaccination with a re...

Background: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the pri...

As part of an ongoing study assessing homologous and heterologous booster vaccines, following primary EUA series, we assessed neutralization of D614G and Omicron variants prior to and 28 days after boost. Subset analysis was done in six combinations (N = 10/group): four homologous primary-booster combinations included mRNA-1273 two-dose priming fol...

Importance The SARS-CoV-2 viral trajectory has not been well characterized in incident infections. These data are needed to inform natural history, prevention practices, and therapeutic development. Objective To characterize early SARS-CoV-2 viral RNA load (hereafter referred to as viral load) in individuals with incident infections in association...

Background The coronavirus disease 2019 (COVID-19) pandemic has challenged researchers performing clinical trials to develop innovative approaches to mitigate infectious risk while maintaining rigorous safety monitoring. Methods In this report we describe the implementation of a novel exclusively remote randomized clinical trial (ClinicalTrials.go...

Background: The National Network of Sexually Transmitted Disease Clinical Prevention Training Centers (NNPTC) trains clinical providers to diagnose and treat sexually transmitted infections (STIs) in the United States. The purpose of this study was to examine the demographics of clinical providers and to correlate the number of training episodes w...

Background While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who h...

Tissue-resident-memory T cells (TRM) populate the body’s barrier surfaces, functioning as frontline responders against reencountered pathogens. Understanding of the mechanisms by which CD8TRM achieve effective immune protection remains incomplete in a naturally recurring human disease. Using laser capture microdissection and transcriptional profili...

Importance: SARS-CoV-2 viral trajectory has not been well-characterized in documented incident infections. These data will inform SARS-CoV-2 natural history, transmission dynamics, prevention practices, and therapeutic development. Objective: To prospectively characterize early SARS-CoV-2 viral shedding in persons with incident infection. Design: P...

The ectocervix is part of the lower female reproductive tract (FRT), which is susceptible to sexually transmitted infections (STI). Comprehensive knowledge of the phenotypes and T cell receptor (TCR) repertoire of tissue resident memory T cells (TRM) in human FRT is lacking. We have taken single-cell RNA sequencing approaches to simultaneously defi...

Epstein-Barr virus (EBV) is transmitted by saliva and is a major cause of cancer, particularly in people living with HIV/AIDS. Here, we describe the frequency and quantity of EBV detection in the saliva of Ugandan adults with and without HIV-1 infection and use these data to develop a novel mathematical model of EBV infection in the tonsils. Eligib...

The National STD Curriculum (NSTDC) is an e-learning platform. New registrations and learning group creations during March-April 2020 were compared to previous 12-month data. Substantial increases in registrations and learning groups demonstrate that the NSTDC was successfully leveraged to meet rapidly shifting training needs due to the COVID-19 pa...

The hypothesis that infectious agents, particularly herpesviruses, contribute to Alzheimer’s disease (AD) pathogenesis has been investigated for decades but has long engendered controversy. In the past 3 years, several studies in mouse models, human tissue models, and population cohorts have reignited interest in this hypothesis. Collectively, thes...

Tissue-based T cells are important effectors in the prevention and control of mucosal viral infections - less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in inflammatory infiltrates in skin biopsies of persons during symptomatic HSV2 reactivation and early healing. Both CD20+ B ce...

Problem Changes in sex hormones during the menstrual cycle and contraceptive vaginal ring (CVR) use influence immunity within the female genital tract, but the magnitude of these effects and their anatomical location are unclear. Method of Study In a prospective study, 29 women were assessed at three time points: follicular phase, luteal phase, an...

Background Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARS-CoV-2 transmission. Methods In this randomized, double-blind, three-arm (1:1:1) placebo-equivalent controlled trial conducted remotely throughout the United States, adult outpatients with laboratory-confirmed SARS-CoV-2 infection were recruited. Part...

Background Prevention interventions for coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are currently limited to non-pharmaceutical strategies. Observational and laboratory data suggested that hydroxychloroquine (HCQ) had biologic activity against SARS-CoV-2. A blinded trial of HCQ in persons...

Background: Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use fo...

Coronavirus disease 2019 (COVID‐19) due to infection with severe acute respiratory syndrome coronavirus 2 causes substantial morbidity. Tocilizumab, an interleukin‐6 receptor antagonist, might improve outcomes by mitigating inflammation. We conducted a retrospective study of patients admitted to the University of Washington Hospital system with COV...

Persons with HIV infection are frequently coinfected with chronic herpesviruses, which periodically replicate and produce viable herpes virions, particularly in anogenital and cervical tissues. Persistent protein expression results in proliferation of CD8 ⁺ and CD4 ⁺ T cells, and the latter could potentially expand and sustain HIV tissue reservoirs...

Background Coronavirus disease 2019 (COVID-19) due to infection with SARS-CoV-2 causes substantial morbidity. Tocilizumab, an interleukin-6 receptor antagonist, might improve outcomes by mitigating inflammation. Methods We conducted a retrospective study of patients admitted to the University of Washington Hospital system with COVID-19 and requirin...

Human herpes simplex viruses (HSV) 1 and 2 are extremely common human pathogens with overlapping disease spectra. Infections due to HSV-1 and HSV-2 are distinguished in clinical settings using sequence-based “typing” assays. Here we describe a case of HSV mistyping caused by a previously undescribed HSV-1 × HSV-2 recombination event in UL27, the HS...

Tissue-based T cells increasingly have been shown to be important effectors in the control and prevention of mucosal viral infections, less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in skin biopsies of persons with symptomatic HSV-2 reactivation. CD20+ B cells are observed in in...

As COVID-19 cases and deaths continue to expand globally, there is an urgent need to develop, test and approve effective antiviral therapies. Currently a majority of clinical trials are evaluating therapies in patients who are already hospitalized with SARS Co-V-2 infection. Given that the median time between development of symptoms and need for ho...

Background Observational studies have suggested increased arrhythmic and cardiovascular risk with the combination use of hydroxychloroquine (HCQ) and azithromycin in patients with coronavirus disease 2019 (COVID-19). Objective The arrhythmic safety profile of HCQ monotherapy, which remains under investigation as a therapeutic and prophylactic agen...

Progressive antimicrobial resistance in Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis has created a pressing need for treatment optimisations for sexually transmitted infections (STIs). In this Review, we aim to highlight urgent needs in global STI management, including: (1) improved surveillance to monitor antimicrobial r...

The large dsDNA virus herpes simplex virus 1 (HSV-1) is considered to be genetically stable, yet it can rapidly evolve in response to strong selective pressures such as antiviral treatment. Deep sequencing has revealed that clinical and laboratory isolates of this virus exist as populations that contain a mixture of minor alleles or variants, simil...

Introduction Herpes simplex virus (HSV) infection can cause painful, recurrent genital ulcer disease (GUD), which can have a substantial impact on sexual and reproductive health. HSV-related GUD is most often due to HSV type 2 (HSV-2), but may also be due to genital HSV type 1 (HSV-1), which has less frequent recurrent episodes than HSV-2. The glob...

Background: With increasing rates of sexually transmitted infections (STIs) in the United States, there is a critical need to educate health professionals on the prevention, diagnosis, and treatment of STIs. The National STD Curriculum (NSTDC, https://www.std.uw.edu) is a free, online curriculum, funded by the Centers for Disease Control and Preve...

Human herpes simplex viruses (HSV) 1 and 2 are most often typed via molecular assays. Here we describe the first known case of HSV mistyping due to a previously undescribed HSV-1 x HSV-2 recombination event in UL27, the gene that encodes glycoprotein B. This is the first reported HSV interspecies recombination event impacting this gene, which is fr...

Background The National Sexually Transmitted Diseases Curriculum (NSTDC) is an online, guideline-based, interactive curriculum developed at the University of Washington in Seattle with funding from the Centers for Disease Control and Prevention (CDC) National Network of STD Clinical Prevention Training Centers (NNPTC). The NSTDC has dual-functional...

Background: Genital herpes simplex virus type-1 (HSV-1) has emerged as the leading cause of first episode genital herpes among specific populations in the U.S., such as adolescents, young adult women, and men who have sex with men (MSM). We examined trends in the etiology of first episode genital herpes diagnoses over time in an STD clinic populat...

The large dsDNA virus HSV-1 is often considered to be genetically stable, however it is known to rapidly evolve in response to strong selective pressures such as antiviral drug treatment. Deep sequencing analysis has revealed that clinical and laboratory isolates of this virus exist as populations that contain a mixture of minor alleles or variants...

Background Women infected with herpes simplex virus type 2 (HSV-2) have increased risk of incident and refractory bacterial vaginosis (BV). We hypothesized that suppression of HSV-2 would be associated with decreased Nugent score and risk of BV. Methods HSV-2 seropositive women with a self-reported history of BV self-collected daily vaginal and an...

Background Genital HSV-1 has surpassed HSV-2 as a cause of first episode genital herpes in high-income settings. To inform counseling messages regarding prevention of genital HSV-1 transmission, we assessed oral and genital shedding patterns among persons with laboratory documented first episode genital HSV-1 infection. Methods Participants with v...

Since 1979, the National Network of STD Clinical Prevention Training Centers (NNPTC) has provided state-of-the-art clinical and laboratory training for sexually transmitted disease (STD) prevention across the United States. This article provides an overview of the history and activities of the NNPTC from its inception to present day, and emphasizes...

Background: The ubiquitous human pathogens, herpes simplex virus (HSV)-1 and HSV-2, are distinct viral species that diverged approximately 6 million years ago. At least 4 small, ancient HSV-1 × HSV-2 interspecies recombination events have affected the HSV-2 genome, with recombinants and nonrecombinants at each locus circulating today. However, it...

Epstein-Barr virus (EBV) infection is transmitted by saliva and is a major cause of cancer in people living with HIV/AIDS as well as in the general population. To better understand the determinants of oral EBV shedding we evaluated the frequency and quantity of detectable EBV in the saliva in a prospective cohort study of 85 adults in Uganda, half...

Mother‐to‐child cytomegalovirus (CMV) breastmilk transmission can occur in the postnatal period. In a pilot study, we measured daily CMV detection by PCR in breastmilk, vaginal, and saliva samples from 9 healthy CMV‐seropositive postpartum women for 28 days. CMV was found in 7 of 9 women and t 171 of 253 breastmilk samples (67.6%). In 4 women, all...

Among the most ubiquitous of human pathogens, HSV-1 and HSV-2 are distinct viral species that diverged about six million years ago. At least four ancient HSV-1 x HSV-2 interspecies recombination events have affected the HSV-2 genome, with recombinants and non-recombinants at each locus circulating today. Though interspecies recombination has occurr...

Background: The effect of female sex hormones on HSV-2 shedding and lesion frequency is poorly understood. Previous studies suggest that hormonal contraception may increase the frequency of HSV-2 shedding. Methods: We studied HSV-2 seropositive women who performed daily genital swabbing for HSV DNA and completed diaries for genital lesions and m...

Contemporary interspecies recombination events occurring in hosts coinfected with both pathogens HSV-1 and HSV-2.

Background: We tested whether genital herpes simplex virus (HSV) shedding is an appropriate surrogate outcome for the clinical outcome of genital herpes lesions in studies of HSV-2 antiviral interventions. Methods: We analyzed prospective data from natural history studies and clinical trials of antiviral agents for HSV-2 in which HSV-2-seroposit...

Here we present genomic and in vitro analyses of temporally separated episodes of herpes simplex virus type 1 (HSV-1) shedding by an HSV-1–seropositive and human immunodeficiency virus (HIV)/HSV-2–seronegative individual who has frequent recurrences of genital HSV-1. Using oligonucleotide enrichment, we compared viral genomes from uncultured swab s...

Herpes simplex viruses affect more than 4 billion people across the globe, constituting a large burden of disease. Understanding the global diversity of herpes simplex viruses is important for diagnostics and therapeutics as well as cure research and tracking transmission among humans. To date, most HSV genomics has been performed on culture isolat...

Herpes simplex viruses (HSV) are difficult to sequence due to their large DNA genome, high GC content, and the presence of repeats. To date, most HSV genomes have been recovered from culture isolates, raising concern that these genomes may not accurately represent circulating clinical strains. We report the development and validation of a DNA oligo...

Humans can be infected sequentially by different strains of the same virus. Estimating the prevalence of so-called 'superinfection' for a particular pathogen is vital because superinfection implies a failure of immunologic memory against a given virus despite past exposure, which may signal challenges for future vaccine development. Increasingly, v...

Background Quantitative estimation of the extent to which the immune system’s protective effect against one herpes simplex virus type 2 (HSV-2) infection protects against infection with additional HSV-2 strains is important for understanding the potential for HSV-2 vaccine development. Using viral genotyping, we estimated the prevalence of HSV-2 du...

Dual-strain infection is underestimated when the observed prevalence is used. (A) The average distance between simulated and observed data in an experimental trial with 20 replicate simulations. The error is minimized when parameter λ is 0.15. (B) The observed data compared directly with the best-fit simulation. About 3% of people observed to have...

Baseline characteristics and GenBank number for samples that underwent HTS. (DOCX)

Data used to make S3 Fig. (CSV)

For each pair of samples, we validated custom array mismatches using HTS by comparing the majority base at each site for the paired samples. The outlier with 22 mismatches by the custom array (GG) and 1 mismatch by sequence is Pair 3, which was excluded from the analysis of superinfected pairs. (TIF)

Oligonucleotides used to create the custom HSV-2 genotyping assay. The nucleotide in brackets represents the SNP of interest. (DOCX)

Sensitivity analysis of risk factors for dual-strain infection, including 8 pairs that were excluded from the analysis due to inability to confirm the 2 samples were from the same person. (DOCX)

Original power calculations and data analysis plan. (DOC)

STROBE checklist indicating adherence to the STROBE guidelines. (DOC)

Demographic information and sexual history information for each participant. People with dual-strain infection are indicated by “1” in column K; those without dual-strain infection detected are as indicated by “0.” The number of mismatches detected by genotyping assay is indicated in column L. (CSV)