A5056778092- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Herpesvirus Infections and Treatments
- HIV/AIDS Research and Interventions
- Parvovirus B19 Infection Studies
- Immune Cell Function and Interaction
- Virology and Viral Diseases
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Viral gastroenteritis research and epidemiology
- COVID-19 Impact on Reproduction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Infant Nutrition and Health
- Respiratory viral infections research
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Vectors
- Vaccine Coverage and Hesitancy
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Blood groups and transfusion
- Immune responses and vaccinations
- Viral Infections and Immunology Research
- Neonatal Health and Biochemistry
Cornell University
2021-2025
Presbyterian Hospital
2021-2025
Weill Cornell Medicine
2021-2025
Duke University
2015-2024
Duke Medical Center
2015-2024
New York Proton Center
2023
Duke University Hospital
2013-2022
New York Hospital Queens
2021-2022
NewYork–Presbyterian Hospital
2021-2022
Durham VA Medical Center
2021
Abstract Infection with Asian-lineage Zika virus (ZIKV) has been associated Guillain–Barré syndrome and fetal abnormalities, but the underlying mechanisms remain poorly understood. Animal models of infection are thus urgently needed. Here we show that rhesus macaques susceptible to by an ZIKV closely related strains currently circulating in Americas. Following subcutaneous inoculation, RNA is detected plasma 1 day post (d.p.i.) all animals ( N =8, including 2 pregnant animals), also present...
Infection with Zika virus (ZIKV) is associated human congenital fetal anomalies. To model outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals a previous study contemporary the current report clear viremia within 10–12 days, maternal was prolonged 3 of 4 pregnancies. Fetal head growth velocity last month gestation determined by ultrasound assessment circumference decreased comparison biparietal diameter...
Threshold regression models are a diverse set of non-regular that all depend on change points or thresholds. They provide simple but elegant and interpretable way to model certain kinds nonlinear relationships between the outcome predictor. The R package chngpt provides both estimation hypothesis testing functionalities for four common variants threshold models. All allow adjustment additional covariates not subjected thresholding. We demonstrate consistency estimating procedures type 1...
Abstract Pediatric vaccines have significantly reduced infectious disease–related infant mortality, but as protective immunity often requires several vaccine doses, maternally acquired Abs are critical to protect infants during the first months of life. Consequently, immunization pregnant women is an important strategy not only mothers from infection, also provide young infants. Nevertheless, maternal can negatively impact early life immunity. In fact, interfere with development immune...
Infections at the maternal-fetal interface can directly harm fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts maternal decidua must provide antimicrobial defenses this critical without compromising its integrity. Here, we developed matched trophoblast (TO) organoids (DO) from human placentas to define relative contributions of these cells antiviral interface. We demonstrate TO DO basally secrete...
MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this design might yield a suitable for licensure.
Pyrazinamide (PZA) is an important front-line anti-tuberculosis drug that active only at acid pH. However, pH causes significant difficulty for PZA susceptibility testing. A common problem in testing false resistance caused by large bacterial inocula. This study investigated the relationship of to numbers bacilli, and other factors potentially affect PZA. Large inocula (107−−8 bacilli/ml) M. tuberculosis H37Ra increase medium from 5.5 towards neutrality, thus produced results. The was...
Human cytomegalovirus (HCMV) is the most common congenital infection worldwide, frequently causing hearing loss and brain damage in afflicted infants. A vaccine to prevent maternal acquisition of HCMV during pregnancy necessary reduce incidence infant disease. The glycoprotein B (gB) + MF59 adjuvant subunit platform successful tested date, demonstrating ∼50% efficacy preventing multiple phase 2 trials. However, mechanism protection remains unknown. Plasma from 33 postpartum women gB/MF59...
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells some encode envelope glycoproteins (Envs) contain fewer potential N-linked glycosylation sites...
Significance The prevention of HIV-1 transmission and progression likely requires approaches that can specifically eliminate HIV-1-infected cells. Rationally designed CD4-mimetic compounds (CD4mc) have been shown to efficiently inhibit viral entry sensitize particles neutralization by otherwise nonneutralizing CD4-induced antibodies. Here we found CD4mc also cells antibody-dependent cell-mediated cytotoxicity (ADCC). Indeed, induced the CD4-bound conformation envelope glycoproteins, exposing...
Background Zika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome adults and congenital birth defects including microcephaly developing fetus. Because development vaccine is top research priority genetic antigenic variability many RNA viruses limits effectiveness vaccines,...
Significance Congenital cytomegalovirus (CMV) is the leading infectious cause of childhood hearing loss and brain damage worldwide. Yet, despite its high prevalence ranking as a top priority for vaccine development, immune correlates protection that could guide development remain undefined. Using novel nonhuman primate model congenital CMV transmission, we demonstrate critical role maternal CD4 + T cells in induction protective responses prevent fetal demise. In addition to establishing...
Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, pediatric hearing loss worldwide. Development maternal vaccine or therapeutic to prevent HCMV has been hindered by limited knowledge immune responses that protect against transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding antiviral functions paired cord blood sera from HCMV-seropositive transmitting (n =...
Human cytomegalovirus (HCMV) is the most common vertically transmitted infection worldwide, yet there are no vaccines or therapeutics to prevent congenital HCMV (cCMV) infection. Emerging evidence indicates that antibody Fc effector functions may be a previously underappreciated component of maternal immunity against HCMV. We recently reported antibody-dependent cellular phagocytosis (ADCP) and IgG activation FcγRI/FcγRII were associated with protection cCMV transmission, leading us...
The pursuit of a vaccine against the human cytomegalovirus (HCMV) has been ongoing for more than 50 years. HCMV is leading infectious cause birth defects, including damage to brain, and common complications in organ transplantation. complex biology made development difficult, but recent meeting sponsored by National Institute Allergy Infectious Diseases September 2023 brought together experts from academia, industry, federal agencies discuss progress field. reviewed status candidate vaccines...
Abstract Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role infection and pathogenesis is unknown. To examine vivo function an animal model evolutionarily closely related to humans, we identified characterized Rh05, Rh152/151 Rh173 as the complete set of vFcγRs encoded by rhesus CMV (RhCMV). Each one these proteins displays functional similarities prospective HCMV orthologs with respect...
Objectives/Goals: We hypothesized that adding cytomegalovirus (CMV) viral Fc gamma receptors (vFcγRs) to a glycoprotein B (gB) protein subunit vaccine would improve vaccine-elicited mediated effector functions such as antibody dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC), over gB alone. Methods/Study Population: immunized rabbits (n = 4 per group) at Weeks 0, 4, 8 with 20μg alone or one vFcgR (gp34, gp68, gp95) 40μg, adjuvanted squalene emusion, Addavax. Plasma from was...
ABSTRACT Despite months of mucosal virus exposure, the majority breastfed infants born to HIV-infected mothers do not become infected, raising possibility that immune factors in milk inhibit transmission HIV. HIV Envelope (Env)-specific antibodies are present mothers, but little is known about their virus-specific functions. In this study, Env-specific antibody binding, autologous and heterologous neutralization, antibody-dependent cell cytotoxicity (ADCC) responses were measured plasma 41...