A5062780201- HIV Research and Treatment
- Immune Cell Function and Interaction
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- Viral Infections and Immunology Research
- Cytomegalovirus and herpesvirus research
- Toxin Mechanisms and Immunotoxins
- COVID-19 Clinical Research Studies
- Glycosylation and Glycoproteins Research
- Mosquito-borne diseases and control
- Viral Infections and Outbreaks Research
- Antiplatelet Therapy and Cardiovascular Diseases
- SARS-CoV-2 and COVID-19 Research
- Galectins and Cancer Biology
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Parasites and Host Interactions
- Platelet Disorders and Treatments
- Heparin-Induced Thrombocytopenia and Thrombosis
Harvard University
2023-2025
Massachusetts General Hospital
2023-2025
University of Minnesota
2020-2024
Central Drug Research Institute
2018-2021
Institute of Parasitology
2016
Abstract HIV-1 envelope glycoproteins (Envs) of most primary strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims mimic the Env as preferred target for eliciting broadly neutralizing antibodies (bnAbs). Here we identify incompletely conformations 6 out 13 transmitted/founder (T/F) that are sensitive recognize epitopes typically exposed on Envs. A 3.6 Å cryo-electron microscopy structure unliganded, T/F...
Immunoglobulin G (IgG) antibodies in the form of high-dose intravenous immunoglobulin (IVIG) exert immunomodulatory activity and are used this capacity to treat inflammatory autoimmune diseases. Reductionist approaches have revealed that terminal sialylation single asparagine-linked (N-linked) glycan at position 297 IgG1 Fc bestows antiinflammatory activity, which can be recapitulated by introduction an F241A point mutation (FcF241A). Here, we examined CHO-K1 cell-produced FcF241A vivo...
Self-antigen-specific T cells are prevalent in the mature adaptive immune system but regulated through multiple mechanisms of tolerance. However, inflammatory conditions such as tissue injury may allow these to break tolerance and trigger autoimmunity. To understand how cell repertoire responds presentation self-antigen under highly stimulatory conditions, we use peptide:major histocompatibility complex (MHC) class II tetramers track behavior endogenous CD4+ with specificity a lung-expressed...
Abstract An effective human immunodeficiency virus type I (HIV-1) vaccine that robustly elicits broadly neutralizing antibodies (bnAbs) against HIV-1 envelope glycoproteins (Envs) to block viral entry is still not available. Thus, identifying triggers for elicitation of different types anti-HIV-1 Env by vaccination could provide further guidance immunogen design and development. Here, we studied the immune response immunogens in rabbits. We show sequential immunizations with...
Platelets, which have been traditionally associated with hemostasis and thrombosis functions, now receive attention for their role in immune responses that may affect vaccine development effectiveness. Through interactions cells modulation of inflammation alongside antigen presentation, platelets become integral components both innate adaptive systems. New research shows can improve effectiveness while reducing adverse side effects. During administration, release cytokines chemokines,...
Platelets, which have been traditionally associated with hemostasis and thrombosis functions, now receive attention for their role in immune responses that may affect vaccine development effectiveness. Through interactions cells modulation of inflammation alongside antigen presentation, platelets become integral components both innate adaptive systems. New research shows can improve effectiveness while reducing adverse side effects. During administration, release cytokines chemokines,...
HIV-1 entry into host cells leads to one of the following three alternative fates: (1) elimination by restriction factors, (2) establishment latency, or (3) active viral replication in target cells. Here, we report development an improved system for monitoring fate at single-cell and population levels show diverse applications this study specific aspects different cell types under environments. An analysis transcriptome infected, primary CD4+ T that support fates identifies differential gene...
HIV-1 envelope glycoproteins (Envs) bind to CD4 receptor and CCR5/CXCR4 coreceptor mediate viral entry (Feng et al., 1996; Herschhorn 2016, 2017; Kwong 1998). Envs are the sole target of neutralizing antibodies a main focus vaccine development (Flemming 2018). Here, we provide step-by-step protocol measure Env sensitivity ligands, cold, small molecules, as well study infectivity dissect parameters affecting function. For complete details on use execution this protocol, please refer Harris al. (2020).
Many HIV strains downregulate the levels of CD4 receptor on surface infected cells to prevent superinfection. In contrast, rare HIV-2UC1 strain is noncytopathic and has no effect expression in but still replicates as efficiently more cytopathic peripheral blood mononuclear (PBMCs). Here, we show that Env interactions with exhibit slow association kinetics, whereas dissociation kinetics within range strains. Despite resulting 10- 100-fold decrease binding affinity, Envs long-lived activation...
Immunotherapy, a treatment based on host immune system activation, has been shown to provide substitute for marginally effective conventional chemotherapy in controlling visceral leishmaniasis (VL), the deadliest form of leishmaniasis. As majority endemic inhabitants exhibit either subclinical or asymptomatic infection which often develops into active disease state, therapeutic intervention seems be an important avenue combating infections by stimulating natural defense infected individuals....
Abstract HIV-1 envelope glycoproteins (Envs) mediate viral entry and are the sole target of neutralizing antibodies. Envs most primary strains exist in a closed conformation occasionally sample more open states. Thus, current knowledge guides immunogen design to mimic Env as preferred for eliciting broadly antibodies (bnAbs) block entry. Here we show that Env-preferred conformations 6 out 13 (46%) transmitted/founder (T/F) tested incompletely closed. As result, these T/Fs into cells is...
Human immunodeficiency virus (HIV-1) envelope glycoproteins (Envs) are a main focus of immunogen design and vaccine development. Broadly neutralizing antibodies (bnAbs) against HIV-1 Envs target conserved epitopes neutralize multiple viral strains. Nevertheless, application bnAbs to therapy prevention is limited by resistant strains that developed or preexist within the population. Here we studied HIV-1NAB9 were isolated from person who injects drugs exhibits high broad resistance bnAbs. We...
The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells requires binding the viral spike glycoprotein to angiotensin-converting enzyme (ACE2) receptor, which triggers subsequent conformational changes facilitate and cellular fusion at plasma membrane or following endocytosis. Here, we experimentally identified selective broad inhibitors SARS-CoV-2 that share a tricyclic ring (or similar) structure. inhibitory effect was restricted early steps during...
Abstract: Visceral leishmaniasis (VL), a phlebotomine-borne neglected tropical disease, is caused by parasites of the Leishmania donovani complex. While L. infection restricted to Indian subcontinent and East Africa, where transmission anthroponotic, infantum occurs in Europe, North parts Latin America, it zoonotic nature with dogs as reservoir hosts. Though incidence VL has been on decline, continues cause epidemics periodically. By large, small proportion manifests clinical disease but...
Available therapeutics for visceral leishmaniasis (VL), a deadly parasitic infection, are usually associated with inadequate efficacy and adverse aftereffects. Further, the primary site of Leishmania parasite host macrophages resulting in compromised immunity; ensuing marked T-cell immunosuppression. Such settings emphasize exploration chemo-immunotherapeutic strategies improvising infected person's immune status better resolution infection.Present work employs immunization...
ABSTRACT HIV-1 entry into host cells leads to one of three alternative fates: 1) elimination by restriction factors, 2) establishment latency, or 3) active viral replication in target cells. Here we developed an improved system for monitoring fate and provide evidence the differential contribution intracellular environment as well extracellular found organs BLT humanized mouse infection.
Summary Self antigen-specific T cells are prevalent in the mature adaptive immune system, but regulated through multiple mechanisms of tolerance. However, inflammatory conditions such as tissue injury may provide these with an opportunity to break tolerance and trigger autoimmunity. To understand how cell repertoire responds presentation self antigen under highly stimulatory conditions, we used peptide:MHCII tetramers track behavior endogenous CD4 + specificity a lung-expressed mouse models...