Lawrence Corey's research while affiliated with University of Washington Seattle and other places

Publications (921)

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Importance The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and suppo...
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In the PREVENT-19 phase 3 trial of the NVX-CoV2373 vaccine (NCT04611802), anti-spike binding IgG concentration (spike IgG), anti-RBD binding IgG concentration (RBD IgG), and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks post-dose two are assessed as correlates of risk and as correlates of protection against COVID-19. Ana...
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Introduction: Sotrovimab, a recombinant human monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had US Food and Drug Administration Emergency Use Authorization for the treatment of high-risk outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19) from 26 May 2021 to 5 April 2022. Real-worl...
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Measuring immune correlates of disease acquisition and protection in the context of a clinical trial is a prerequisite for improved vaccine design. We analysed binding and neutralizing antibody measurements 4 weeks post vaccination as correlates of risk of moderate to severe-critical COVID-19 through 83 d post vaccination in the phase 3, double-bli...
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Background Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV. Methods This placebo-controlled, double-blind, phase 1/2a study (NCT02935686) enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding...
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A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, IV remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to f...
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Adoptive therapy with genetically engineered T cells offers potential for infectious disease treatment in immunocompromised persons. HIV/simian immunodeficiency virus (SIV) infected cells express phosphatidylserine (PS) early post-infection. We tested whether chimeric engulfment receptor (CER) T cells designed to recognize PS-expressing cells could...
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People living with HIV-1 (PLWH) exhibit more rapid antibody decline following routine immunization and elevated baseline chronic inflammation than people without HIV-1 (PWOH), indicating potential for diminished humoral immunity during SARS-CoV-2 infection. Conflicting reports have emerged on the ability of PLWH to maintain humoral protection again...
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Seven viruses cause at least 15% of the total cancer burden. Viral cancers have been described as the "low-hanging fruit" that can be potentially prevented or treated by new vaccines that would alter the course of global human cancer. Kaposi sarcoma herpesvirus (KSHV or HHV8) is the sole cause of Kaposi sarcoma, which primarily afflicts resource-po...
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Background We report updated safety, efficacy, and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) from an ongoing phase 3 trial.Methods Adults at increased risk of SARS-CoV-2 infection were randomized (2:1), stratified by age, to receive 2 doses of AZD1222 or placebo. The primary efficacy end point was confirmed SARS-CoV-2 reverse-transcriptase PCR-po...
Preprint
Background Sotrovimab, a recombinant human monoclonal antibody (mAb) against SARS-CoV-2 had US FDA Emergency Use Authorization (EUA) for the treatment of high-risk outpatients with mild-to-moderate COVID-19 from May 26, 2021, to April 5, 2022. The study objective was to evaluate the real-world effectiveness of sotrovimab in reducing the risk of 30-...
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Importance: With timely collection of SARS-CoV-2 viral genome sequences, it is important to apply efficient data analytics to detect emerging variants at the earliest time. Objective: To evaluate the application of a statistical learning strategy (SLS) to improve early detection of novel SARS-CoV-2 variants using viral sequence data from global...
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The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT 80 ) biomarker—which quantifies the neutralization potency...
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Background: Herpes simplex virus lymphadenitis (HSVL) is an unusual presentation of HSV reactivation in chronic lymphocytic leukemia (CLL) patients characterized by systemic symptoms and no herpetic lesions. The immune responses during HSVL have not been studied. Methods: Peripheral blood and lymph node samples of a patient with HSVL were obtain...
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Background: Immunoassays for determining past SARS-CoV-2 infection have not been systematically evaluated in vaccinated persons in comparison with unvaccinated persons. Objective: To evaluate antinucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 (Moderna) vaccinees with breakthrough SARS-CoV-2 infection. Design: Nested substudy of...
Article
Background The ALVAC/gp120 + MF59 vaccines in the HVTN 702 efficacy trial did not prevent HIV-1 acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition. Methods Among 1893 HVTN 702 female vaccinees, 60 HIV-1-seropositive...
Preprint
Adoptive therapy with genetically engineered T cells offers potential for infectious disease treatment in immunocompromised persons. HIV/simian immunodeficiency virus (SIV) infected cells express phosphatidylserine (PS) early post-infection. We tested whether chimeric engulfment receptor (CER) T cells designed to recognize PS-expressing cells could...
Preprint
In the randomized, placebo-controlled PREVENT-19 phase 3 trial conducted in the U.S. and Mexico of the NVX-CoV2373 adjuvanted, recombinant spike protein nanoparticle vaccine, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks after two doses were assessed as correlates of r...
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This cohort study assesses the durability of protection against symptomatic COVID-19 among participants of the mRNA-1273 SARS-CoV-2 (Moderna) vaccine trial.
Preprint
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Importance The performance of immunoassays for determining past SARS-CoV-2 infection, which were developed in unvaccinated individuals, has not been assessed in vaccinated individuals. Objective To evaluate anti-nucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 vaccine efficacy trial participants after SARS-CoV-2 infection during the t...
Preprint
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Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-...
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The remarkable success of the US government backed COVID-19 vaccine development in 2020 offers several lessons on how to effectively foster rapid vaccine discovery and development. Conceptually, the formation of a public private partnership that included innovative government and academic involvement at all levels of the program was instrumental in...
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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...
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We report a 23% asymptomatic SARS CoV-2 Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T-cell counts in persons with HIV strongly correlated with increased odds of being SARS-CoV-2 PCR positive.
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Since the beginning of the SARS‐CoV‐2 pandemic, antibody responses and antibody effector functions targeting SARS‐CoV‐2‐infected cells have been understudied. Consequently, the role of these types of antibodies in SARS‐CoV‐2 disease (COVID‐19) and immunity is still undetermined. To provide tools to study these responses, we used plasma from SARS‐Co...
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Background: The Ad26.COV2.S vaccine was highly effective against severe-critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis. Methods: We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in...
Preprint
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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...
Article
The rapid development of COVID-19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically...
Preprint
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The early widespread dissemination of Omicron indicates the urgent need to better understand the transmission dynamics of this variant, including asymptomatic spread among immunocompetent and immunosuppressed populations. In early December 2021, the Ubuntu clinical trial, designed to evaluate efficacy of the mRNA-1273 vaccine (Moderna) among person...
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Background: The AMP studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized Phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring pre-medication and limiting their...
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Background NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b–3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. Methods We conducted a phase 3, randomized...
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Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we...
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Background People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus...
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Background SARS-CoV-2 vaccine efficacy (VE) against asymptomatic infection and impact on viral shedding during breakthrough infections have critical implications for pandemic control. AZD1222 (ChAdOx1 nCoV-19; 2 doses, 4 weeks apart) demonstrated VE of 74.0% (95% CI 65.3, 80.5) against the primary endpoint of symptomatic RT-PCR-confirmed COVID-19 a...
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A cornerstone of HIV prevention clinical trials is providing a combination prevention package to all trial participants. The elements included in that standard of care (SoC) package evolve as new prevention modalities are developed. Pre-exposure prophylaxis (PrEP) was recommended by the World Health Organization for persons at high risk of acquirin...
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Antibody levels predict vaccine efficacy Symptomatic COVID-19 infection can be prevented by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. A “correlate of protection” is a molecular biomarker to measure how much immunity is needed to fight infection and is key for successful global immunization programs. Gilbert et al . dete...
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Background Activated T cells have limited antigen presenting capability due to inefficient capture. ¹ This process can be enhanced through novel chimeric engulfment receptors (CERs) expressing a human Tim-4 phagocyte receptor that recognizes phosphatidylserine (Ptd-Ser) ² fused to T cell and macrophage/dendritic cell-derived signaling domains. CERs...
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Introduction The last 12 years have seen remarkable progress in the isolation and characterization of at least five different epitope classes of HIV-specific broadly neutralizing antibodies (bnAbs). Detailed analyses of these bnAb lineages, maturation pathways and epitopes have created new opportunities for vaccine development. In addition, interes...
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The human Betacoronavirus OC43 is a common cause of respiratory viral infections in adults and children. Lung infections with OC43 are associated with mortality, especially in hematopoietic stem cell transplant recipients. Neutralizing antibodies play a major role in protection against many respiratory viral infections, but to date a live viral neu...
Preprint
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BACKGROUND Vaccination using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein antigen has been effective in the prevention of coronavirus disease 2019 (Covid-19). NVX-CoV2373 is an adjuvanted, recombinant S protein nanoparticle vaccine that demonstrated clinical efficacy for prevention of Covid-19 in phase 2b/3 trials...
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Background The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. Methods In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical tri...
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SARS-CoV-2 vaccine clinical trials assess efficacy against disease (VEDIS), the ability to block symptomatic COVID-19. They only partially discriminate whether VEDIS is mediated by preventing infection completely, which is defined as detection of virus in the airways (VESUSC), or by preventing symptoms despite infection (VESYMP). Vaccine efficacy a...
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Background At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from t...
Preprint
Full-text available
Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States Government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we...
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Full-text available
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...
Preprint
Full-text available
Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States Government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we...
Preprint
Full-text available
Background: In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. Methods: Through case-cohort sampling, participants were selected for measurement of four serum a...
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Determinants of protective immunity against SARS-CoV-2 infection require the development of well-standardized, reproducible antibody assays. This need has led to the emergence of a variety of neutralization assays. Head-to-head evaluation of different SARS-CoV-2 neutralization platforms could facilitate comparisons across studies and laboratories....
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VRC01 is being evaluated in the AMP efficacy trials, the first assessment of a passively administered broadly neutralizing monoclonal antibody (bnAb) for HIV-1 prevention. A key analysis will assess serum VRC01-mediated neutralization as a potential correlate of protection. To prepare for this analysis, we conducted a pilot study where we measured...
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There is a realistic expectation that the global effort in vaccination will bring the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic under control. Nonetheless, uncertainties remain about the type of long-term association the virus will establish with the human population, particularly whether the coronavirus disease 2019 (CO...
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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...
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Chimeric antigen receptor (CAR) T cells are engineered cells used in cancer therapy and are studied to treat infectious diseases. Trafficking and persistence of CAR T cells is an important requirement for efficacy to target cancer. Here, we describe a CAR RNA FISH histo-cytometry platform combined with a random reaction seed image analysis algorith...
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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...
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We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell...
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Chimeric antigen receptor (CAR) T-cell therapies are being investigated as potential HIV cures and designed to target HIV reservoirs. Monoclonal antibodies targeting the simian immunodeficiency virus (SIV) envelope allowed us to investigate the potency of single chain variable fragment (scFv)-based anti-SIV CAR T cells. In vitro, CAR T cells expres...
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Background The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation. Methods Download a PDF of the Research Summary. In an international, randomized, double-blind, placebo-c...
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Multiple candidate vaccines to prevent COVID-19 have entered large-scale phase 3 placebo-controlled randomized clinical trials, and several have demonstrated substantial short-term efficacy. At some point after demonstration of substantial efficacy, placebo recipients should be offered the efficacious vaccine from their trial, which will occur befo...
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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...
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Background A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox–protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1–2a tr...
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Background Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear. Methods We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Part...
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Background: HIV Vaccine Trials Network (HVTN) 703/HIV Prevention Trials Network (HPTN) 081 is a phase 2b randomized, double-blind placebo-controlled trial to assess the safety and efficacy of passively infused monoclonal antibody (mAb) VRC01 in preventing HIV acquisition in heterosexual women between the ages of 18 and 50 at risk of HIV. Participa...
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Background: The Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 & HVTN 703/HPTN 081) are the first efficacy trials to evaluate whether VRC01, a broadly neutralizing monoclonal antibody (mAb) targeting the CD4 binding site of the HIV envelope protein, prevents sexual transmission of HIV-1. HVTN 704/HPTN 085 enrolled 2,701 cisgender men...
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The phase 2b AMP trials are testing whether the broadly neutralising antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modelling of longitudinal serum VRC01 concentrations to characterise...
Article
A large number of studies are being conducted to evaluate the efficacy and safety of candidate vaccines against novel coronavirus disease-2019 (COVID-19). Most Phase 3 tri- als have adopted virologically confirmed symptomatic COVID-19 disease as the primary efficacy endpoint, although laboratory-confirmed SARS-CoV-2 is also of interest. In addi- ti...
Preprint
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Background Several candidate vaccines to prevent COVID-19 disease have entered large-scale phase 3 placebo-controlled randomized clinical trials and some have demonstrated substantial short-term efficacy. Efficacious vaccines should, at some point, be offered to placebo participants, which will occur before long-term efficacy and safety are known....
Preprint
Full-text available
Ongoing SARS-CoV-2 vaccine trials assess vaccine efficacy against disease (VE DIS ), the ability of a vaccine to block symptomatic COVID-19. They will only partially discriminate whether VE DIS is mediated by preventing infection as defined by the detection of virus in the airways (vaccine efficacy against infection defined as VE SUSC ), or by prev...
Preprint
Determinants of protective immunity against SARS-CoV-2 infection require the development of well-standardized, reproducible antibody assays to be utilized in concert with clinical trials to establish correlates of risk and protection. This need has led to the appearance of a variety of neutralization assays used by different laboratories and compan...