Nadine Rouphael

Nadine Rouphael
Emory University | EU · Division of Infectious Diseases

MD

About

144
Publications
19,352
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
13,956
Citations

Publications

Publications (144)
Preprint
Background Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. Methods This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a si...
Preprint
Over the last decade, the field of systems vaccinology has emerged, in which high throughput transcriptomics and other omics assays are used to probe changes of the innate and adaptive immune system in response to vaccination. RNA-Seq technology has matured in recent years and is now widely deployed for transcriptional analysis of clinical specimen...
Article
Background Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. Methods In this random...
Preprint
Waning immunity after two SARS-CoV-2 mRNA vaccinations and the emergence of variants precipitated the need for booster doses. We evaluated safety and serological and cellular immunogenicity through 6 months after a third mRNA vaccination in adults who received the mRNA-1273 primary series in the Phase 1 trial approximately 9 to 10 months earlier. T...
Article
Full-text available
Background Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modif...
Article
Full-text available
While the development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines was rapid, time to development and implementation challenges remain that may impact the response to future pandemics. Trained immunity via bacille Calmette-Guerin (BCG) vaccination (an antigen agnostic strategy) offers a potential intervention against fut...
Article
Background We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection and two-injection dosing schedule in a previous phase 1–2 study. Based on interim results from that study, we selected a two-injection schedule and the AS03 adjuvant for further clinical d...
Article
Background Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. Methods We did a double-blind,...
Article
Full-text available
SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the impact of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and ACE2-competing antibodies elicited by th...
Article
Full-text available
In a phase 1 randomized, single-center clinical trial, inactivated influenza virus vaccine delivered through dissolvable microneedle patches (MNPs) was found to be safe and immunogenic. Here, we compare the humoral and cellular immunologic responses in a subset of participants receiving influenza vaccination by MNP to the intramuscular (IM) route o...
Article
Full-text available
Purpose of Review Coronavirus disease 2019 (COVID-19) is caused by a complex interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics and host immune responses. Hosts with altered immunity, including solid organ transplant recipients, may be at increased risk of complications and death due to COVID-19. A synthesis of...
Preprint
Full-text available
SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, and the durability of such responses has not been previously reported. Here, we present a comprehensive assessment of the impact of variants B.1.1.7, B.1.351, P.1, B.1.429, and B.1.526 on binding, neutralizing, and ACE2-blocking antibodies elicited by the vaccine mRNA-12...
Article
Full-text available
Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)...
Article
Full-text available
BACKGROUND Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults w...
Article
Background: Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. Methods: We conducted a phase 1, dose-escalation, op...
Article
Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. Methods We conducted a phase 1, dose-escalation, open-label trial...
Article
Background: The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study is conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the US. Methods: We conducted a 10-year (2005-2015)...
Article
The last decade has witnessed tremendous progress in immunology and vaccinology, owing to several scientific and technological breakthroughs. Systems vaccinology is a field that has emerged at the forefront of vaccine research and development and provides a unique way to probe immune responses to vaccination in humans. The goals of systems vaccinol...
Article
Full-text available
Background HIV vaccine trials routinely measure multiple vaccine-elicited immune responses to compare regimens and study their potential associations with protection. Here we employ unsupervised learning tools facilitated by a bidirectional power transformation to explore the multivariate binding antibody and T-cell response patterns of immune resp...
Article
Full-text available
A laboratory worker suffered an accidental needle-stick resulting in an exposure to the Ugandan strain (MR766) of Zika virus, which has rarely been studied in humans. We report the clinical presentation and outcomes, molecular and serological diagnostic results, and antibody response.
Article
Full-text available
BACKGROUNDRV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of regimens substituting the DNA-HIV-PT123 (DNA) vaccine for ALVAC-HIV in different sequences or com...
Article
Emerging evidence indicates a central role for the microbiome in immunity. However, causal evidence in humans is sparse. Here, we administered broad-spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination. Despite a 10,000-fold reduction in gut bacterial load and long-lasting diminution in bacterial diversity,...
Article
Filociclovir (MBX-400, cyclopropavir) is an antiviral agent with activity against cytomegalovirus (CMV). A phase 1, double blind, randomized, placebo-controlled (3:1 ratio), single center, multiple ascending dose trial was conducted to assess the safety, tolerability, and pharmacokinetics of filociclovir. Filociclovir (n=18) or placebo (n=6) were a...
Article
Data from 1174 infants enrolled in a previous rotavirus vaccine study were analyzed to determine the effect of antibiotic exposure (from 14 days before to 7 days after vaccination) on rotavirus serum immunoglobulin A (IgA) responses. Serum IgA responses 1 month after the completion of vaccination were similar among antibiotic-exposed and nonexposed...
Article
Full-text available
Liquid-chromatography mass spectrometry is commonly used to identify and quantify metabolites from biological samples to gain insight into human physiology and pathology. Metabolites and their abundance in biological samples are labile and sensitive to variations in collection conditions, handling and processing. Variations in sample handling could...
Article
Full-text available
Objectives: Novel approaches to advance the field of vaccinology must be investigated, and are particularly of importance for influenza in order to produce a more effective vaccine. A systematic review of human challenge studies for influenza was performed, with the goal of assessing safety and ethics and determining how these studies have led to t...
Article
Full-text available
Background: Vaccination of children with 13-valent pneumococcal conjugate vaccine (PCV13) led to declines in vaccine-type pneumococcal nasopharyngeal carriage among adults through indirect effects. In August 2014, PCV13 immunization of all U.S. adults ≥65 years of age was recommended. This study sought to define prevalence and serotype distributio...
Article
Full-text available
Streptococcus pneumoniae is a highly impactful bacterial pathogen on a global scale. The principal pneumococcal virulence factor and target of effective vaccines is its polysaccharide capsule, of which there are many structurally distinct forms. Here, we describe four distinct strains of three Mitis group commensal species (Streptococcus infantis,...
Data
Assignment of study strains to species employing phylogenetic clustering of concatenated housekeeping genes as previously described (Bishop et al., 2009). Where not labeled the sequences were obtained from this study and shared the same species clustering. Methodology follows this paper exactly, except that only the four closest species clusters to...
Data
General features of additional homologs of cps loci from non-pneumococcal species (SO, S. oralis; SM, S. mitis) compared to pneumococci of known capsular serotypes. The genes aligned by the slanted lines indicate the polysaccharide synthetic gene cluster. Within each gene of the cluster, the percent identity between the two homologs is shown. In ea...
Article
Full-text available
The re-emergence of Zika virus (ZIKV) in the western hemisphere has most significantly affected dengue virus (DENV) endemic regions. Due to the geographical overlap between these two closely related flaviviruses, numerous individuals who suffered ZIKV infection during recent outbreaks may have also previously been exposed to DENV. As such, the impa...
Article
Full-text available
Abstract Streptococcus pneumoniae’s polysaccharide capsule is an important virulence factor; vaccine-induced immunity to specific capsular polysaccharide effectively prevents disease. Serotype 1 S. pneumoniae is rarely found in healthy persons, but is highly invasive and a common cause of meningitis outbreaks and invasive disease outside of the Uni...
Article
Full-text available
Background Clinical, virologic and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. Methods US-subjects with suspected ZIKV infection were enrolled. Clinical data and specimens were prospectively collected for ZIKV RNA detection, and serologic and cellular assays. Confirmed ZIKV infection (cases) and Z...
Article
Full-text available
Background The clinical, virologic and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. Methods US patients with suspected Zika virus (ZIKV) infection were enrolled and clinical data and specimens were prospectively collected. Body fluids were tested for ZIKV RNA by PCR and blood was tested using serol...
Article
Full-text available
A 74-year-old man presented to the emergency department with severe right leg cellulitis following a trip to the Bahamas where he swam in both chlorinated pools and the ocean. His blood cultures grew Shewanella species, a marine pathogen known to cause disease in humans, following exposure to seawater. He was treated with cefepime for a total of tw...
Article
Reply to “A refugee patient with meningococcal meningitis type B.”
Article
Herpes zoster (HZ) (shingles) is the clinical manifestation of varicella-zoster virus (VZV) reactivation. HZ typically develops as people age, due to decreased cell-mediated immunity. However, the importance of antibodies for immunity against HZ prevention remains to be understood. The goal of this study was to examine the breadth and functionality...
Article
Full-text available
The control of meningitis, meningococcemia and other infections caused by Neisseria meningitidis is a significant global health challenge. Substantial progress has occurred in the last twenty years in meningococcal vaccine development and global implementation. Meningococcal protein-polysaccharide conjugate vaccines to serogroups A, C, W, and Y (mo...
Article
We studied the relationship between varicella-zoster virus (VZV) DNAemia and development of VZV-specific immunity after administration of live-attenuated zoster vaccine. VZV-DNAemia, detected by polymerase chain reaction (PCR), and VZV-specific effector (Teff) and memory (Tmem) T cells, was measured in 67 vaccinees. PCR was positive in 56% (9 direc...
Article
Background: The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. Methods: We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three cent...
Article
Introduction: In older adults, prior administration of 23-valent pneumococcal polysaccharide vaccine (PPSV23) blunts the opsonophagocytic antibody (OPA) response to subsequent administration of 13-valent pneumococcal conjugate vaccine (PCV13). To determine whether a higher dose of PCV13 could mitigate this effect in adults 55 through 74 years of a...
Article
Full-text available
Background: There is an urgent need for studies of viral persistence and immunity during human Zika infections to inform planning and conduct of vaccine clinical trials. Methods: In five returned US travelers with acute symptomatic Zika infection, clinical features, viral RNA levels, and immune responses were characterized. Results: Two pregna...
Article
Full-text available
Background: Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practic...
Article
Full-text available
During the current Zika virus (ZIKV) outbreak, acute symptomatic ZIKV infection in adults appears to be a mild to moderate self-limited illness. We present a case of ZIKV rash illness that improved and then relapsed without repeat exposure to ZIKV. Clinicians should be alert for relapses in patients with ZIKV infection.
Article
The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in old...
Article
Background Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against...
Article
Full-text available
Despite the widespread outbreak, few cases of Zika associated with cardiac manifestations have been described. We present a case of pericarditis in the setting of an acute, symptomatic Zika virus infection in a traveler returning from St. Thomas. Clinicians should be alert for this potential complication of Zika virus infection.
Article
Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy you...
Article
Introduction: To guide the use of modified vaccinia Ankara (MVA) vaccine in response to a release of smallpox virus, the immunogenicity and safety of shorter vaccination intervals, and administration by jet injector (JI), were compared to the standard schedule of administration on Days 1 and 29 by syringe and needle (S&N). Methods: Healthy adult...
Article
Full-text available
Background. Mortality for cryptococcal meningitis remains significant, in spite of available treatment. Resistance to first-line maintenance therapy, particularly fluconazole, has been reported. Methods. A retrospective chart review was performed on immunocompromised patients with cryptococcal meningitis, who had susceptibility testing performed be...
Article
Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influ...
Article
Full-text available
Background. We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods. Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation stud...
Article
Full-text available
Background. Variant influenza A(H3N2) viruses (H3N2v) have transmitted recently from pigs to humans in the United States. Vaccines strategies are needed. Methods. Healthy adults received 2 doses of subvirion H3N2v vaccine (15 µg of hemagglutinin/dose) 21 days apart in this open-label trial. Serum hemagglutination inhibition (HAI) and neutralizing (...
Article
Full-text available
Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs. A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of in...