A5020311779- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS drug development and treatment
- Respiratory viral infections research
- COVID-19 Clinical Research Studies
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- vaccines and immunoinformatics approaches
- Immunodeficiency and Autoimmune Disorders
- Virology and Viral Diseases
- Monoclonal and Polyclonal Antibodies Research
- Infant Nutrition and Health
- Cytomegalovirus and herpesvirus research
- Breastfeeding Practices and Influences
- Influenza Virus Research Studies
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- HIV-related health complications and treatments
- SARS-CoV-2 detection and testing
- Ocular Surface and Contact Lens
- Plant Virus Research Studies
- Probiotics and Fermented Foods
Dartmouth College
2008-2024
Dartmouth Health
2023-2024
Dartmouth–Hitchcock Medical Center
2006-2023
Dartmouth Hospital
2022
White River Junction VA Medical Center
2009
Aaron Diamond AIDS Research Center
1995-2006
Rockefeller University
1995-2005
Cornell University
2002
University of Rochester Medical Center
1998
Saint Louis University
1998
Recent studies have identified several coreceptors that are required for fusion and entry of Human Immunodeficiency Virus type 1 (HIV-1) into CD4+ cells. One these receptors, CCR5, serves as a coreceptor nonsyncytium inducing (NSI), macrophage-tropic strains HIV-1, while another, fusin or CXCR-4, functions T cell line–adapted, syncytiuminducing (SI) strains. Using sequential primary isolates we examined whether viruses using emerge in vivo changes use associated with disease progression. We...
HIV-1 vpr encodes a 96-amino acid, nuclear protein whose function is not well understood. Unlike the other lentivirus regulatory proteins, Vpr present in virions at relatively high copy number. In cells, localized to nucleus. Possible functions for consistent with these findings include import of preintegration complexes, transactivation cellular genes, or induction differentiation. We show here, using both replication competent, macrophage-tropic virus and sensitive, single-cycle luciferase...
The rate of clinical progression is variable among individuals infected with human immunodeficiency virus type 1 (HIV-1). Changes in viral burden which correlate disease status have been demonstrated cross-sectional studies; however, a detailed longitudinal study the temporal relationship between burden, CD4+ T-cell numbers, and throughout course infection has not reported. Multiple blood samples were obtained from four HIV-1-infected clinically divergent profiles. Levels HIV-1 measured...
The product of the vpr open reading frame human immunodeficiency virus type 1 (HIV-1) is a 15-kDa, arginine-rich protein that present in virions molar quantities equivalent to Gag. We report here results our investigations into mechanism by which Vpr incorporated during assembly infected cells. For these studies we used an expression vector encoding molecule fused at its amino terminus nine-amino-acid peptide from influenza hemagglutinin. tagged and mutant HIV-1 provirus were cotransfect COS...
A comprehensive understanding of the kinetics and evolution human B cell response to SARS-CoV-2 infection will facilitate development next-generation vaccines therapies. Here, we longitudinally profiled this in mild severe COVID-19 patients over a period five months. Serum neutralizing antibody (nAb) responses waned rapidly but spike (S)-specific IgG+ memory cells (MBCs) remained stable or increased time. Analysis 1,213 monoclonal antibodies (mAbs) isolated from S-specific MBCs revealed...
Identification of risk factors severe coronavirus disease 2019 (COVID-19) is critical for improving therapies and understanding acute respiratory syndrome 2 (SARS-CoV-2) pathogenesis. We analyzed 184 patients hospitalized COVID-19 in Livingston, New Jersey clinical characteristics associated with disease. The majority had diabetes mellitus (DM) (62.0%), Pre-DM (23.9%) elevated fasting blood glucose (FBG), or a body mass index >30 normal hemoglobin A1c (HbA1C) (4.3%). SARS-CoV-2 infection was...
Understanding humoral immune responses to SARS-CoV-2 infection will play a critical role in the development of vaccines and antibody-based interventions. We report systemic mucosal antibody convalescent individuals who experienced varying severity disease. Whereas assessment neutralization antibody-mediated effector functions revealed polyfunctional serum, only robust phagocytosis were apparent nasal wash samples. Serum correlated with SARS-CoV-2-specific IgG response magnitude, while was...
We examined the replicative properties of a series sequential isolates and biological clones human immunodeficiency virus type 1 (HIV-1) obtained from an individual who progressed seroconversion to AIDS in approximately 5 years. HIV-1 isolated soon after replicated slowly low levels cultures peripheral blood mononuclear cells; however, subsequent during asymptomatic infection showed marked increase replication kinetics. This was more detail by using panel 35 generated patient cell samples....
ABSTRACT We have studied 18 participants in phase I/II clinical trials of recombinant gp120 (rgp120) subunit vaccines (MN and SF-2) who became infected with human immunodeficiency virus type 1 (HIV-1) during the course trials. Of individuals, 2 had received a placebo vaccine, 9 been immunized MN rgp120, seven SF-2 rgp120. Thirteen vaccinees three or four immunizations prior to becoming infected. these, two were recipients, six five Only 11 rgp120 recipients multiple failed develop strong...
Convalescent plasma has been deployed globally as a treatment for COVID-19, but efficacy mixed. Better understanding of the antibody characteristics that may contribute to its antiviral effects is important this intervention well offer insights into correlates vaccine-mediated protection.
Abstract Background A longitudinal study was performed to determine the breadth, kinetics, and correlations of systemic mucosal antibody responses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods Twenty-six unvaccinated adults with confirmed disease 2019 (COVID-19) were followed for 6 months 3 collections blood, nasal secretions, stool. Control samples obtained from 16 uninfected individuals. SARS-CoV-2 neutralizing binding respectively evaluated by pseudovirus...
Preexisting antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential influence antibody response COVID-19 vaccination and infection for better or worse. In this observational study of mucosal systemic humoral immunity in acutely infected, convalescent, vaccinated subjects, we tested cross-reactivity against CoV spike (S) protein at subdomain resolution. Elevated responses, particularly β-CoV OC43, were observed all natural cohorts correlated SARS-CoV-2....
The role of CD8(+) T lymphocytes in controlling replication live, attenuated simian immunodeficiency virus (SIV) was investigated as part a vaccine study to examine the correlates protection SIV/rhesus macaque model. Rhesus macaques immunized for >2 yr with nef-deleted SIV (SIVmac239Deltanef) and protected from challenge pathogenic SIVmac251 were treated anti-CD8 antibody (OKT8F) deplete cells vivo. effects CD8 depletion on viral load measured using novel quantitative assay based real-time...
ABSTRACT Despite evidence that live, attenuated simian immunodeficiency virus (SIV) vaccines can elicit potent protection against pathogenic SIV infection, detailed information on the replication kinetics of in vivo is lacking. In this study, we measured RNA plasma 16 adult rhesus macaques immunized with a strain (SIVmac239Δnef). To evaluate relationship between vaccine and onset protection, four animals per group were challenged SIVmac251 at either 5, 10, 15, or 25 weeks after immunization....
Background Development of a tuberculosis vaccine to boost BCG is major international health priority. SRL172, an inactivated whole cell booster derived from non-tuberculous mycobacterium, the only new against have demonstrated efficacy in Phase 3 trial. In present study we sought determine if three-dose series DAR-901 manufactured SRL172 master bank by new, scalable method was safe and immunogenic. Methods We performed single site, randomized, double-blind, controlled, 1 dose escalation...
Clinical deterioration in human immunodeficiency virus type 1 (HIV-1) disease is associated with an increased viral burden the peripheral blood and a loss of circulating CD4+ T cells. HIV-1 isolates obtained prior to this stage often have "slow-low," non-syncytium-inducing (NSI) phenotype, whereas those afterwards are characterized as "rapid-high" syncytium inducing (SI). Paired NSI SI from two different patients were inoculated into thymus implants SCID-hu mice. The slow-low, replicated...
Identification of mechanisms that limit poliovirus replication is crucial for informing decisions aimed at global polio eradication. Studies mucosal immunity induced by oral (OPV) or inactivated (IPV) vaccines and mixed schedules thereof will determine the effectiveness different vaccine strategies to block virus shedding. We used samples from a clinical trial vaccination measure intestinal as judged neutralisation virus-specific IgA in stools.In FIDEC trial, Latin American infants were...
The prognostic significance of SIV plasma viral load in macaques has not been well established, primarily owing to the small numbers animals experimental groups. In addition, many investigators have noted that fail develop an anti-SIV humoral response disease rapidly. To establish and seroconversion, we retrospectively analyzed serology data from 74 rhesus infected with SIVmac. Viral was at three time points: peak (days 7-21), acute 30-55), chronic 80-100) periods postinfection. High phases...
Among 2099 uninfected subjects in phase I and II trials of candidate AIDS vaccines, 23 were diagnosed with intercurrent human immunodeficiency virus type 1 (HIV-1) infection. High-risk sexual exposures accounted for 17 infections, intravenous drug use 6. Four received placebo, 13 a complete immunization schedule (⩾3 injections), 6 partially immunized (⩽2 injections). There was no significant difference between vaccine recipients control groups incidence HIV-1 infection, load, CD4 lymphocyte...
Despite multiple, high-risk sexual exposures, some individuals remain uninfected with human immunodeficiency virus type 1 (HIV-1). CD4+ lymphocytes from these are less susceptible to infection in vitro strains of HIV-1, suggesting that the phenotype may influence its ability interact certain cells. In present study, we examined susceptibility T and macrophages two exposed (EU2 EU3) a panel biologically cloned isolates HIV-1 having either non-syncytium-inducing (NSI) or syncytium-inducing...
Two sCD4-resistant, primary viruses (P-08 and P-17) were compared with two sCD4-sensitive, T cell line-adapted variants (C-08 C-17) for their biochemical responses to sCD4. At 37°C, neither virus shed gp120 within 8 hr at sCD4 concentrations of up 500 nM, whereas C-08 C-17 lost minutes addition 5-10 nM 4°C, however, P-17 similar rates in response the same concentration. Irrespective temperature, dissociation from both was inhibited by CD4 MAbs 6H10 5A8, latter which blocks events subsequent...
Human breastmilk provides a rich source of commensal lactic acid bacteria (LAB) to the infant during breastfeeding and stimulates abundant growth colonization these at mucosal surfaces in gastrointestinal tract. While conferring critical nutritional immunologic support developing newborn, also serves as vehicle for human immunodeficiency virus type 1 (HIV-1) transmission from mother child breastfeeding. Whether LAB confer protection against exposure HIV-1 infants is unknown.In present study,...