A5024935433- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Immune Cell Function and Interaction
- Viral Infections and Outbreaks Research
- Immune Response and Inflammation
- Single-cell and spatial transcriptomics
- vaccines and immunoinformatics approaches
- Rabies epidemiology and control
- Microbial infections and disease research
- Influenza Virus Research Studies
- HIV Research and Treatment
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Immune responses and vaccinations
- Bacteriophages and microbial interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- Virology and Viral Diseases
Karolinska University Hospital
2017-2025
Karolinska Institutet
2017-2025
University of Washington
2024-2025
ENT and Allergy
2018-2020
Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine available. Elucidation of the prefusion structure RSV F glycoprotein and its identification as main target neutralizing antibodies have provided new opportunities development an effective vaccine. Here, we describe structure-based design self-assembling protein nanoparticle presenting prefusion-stabilized variant trimer (DS-Cav1) in repetitive array on exterior. The two-component nature scaffold...
mRNA vaccines are rapidly emerging as a powerful platform for infectious diseases because they well tolerated, immunogenic, and scalable built on precise but adaptable antigen design. We show that two immunizations of modified non-replicating encoding influenza H10 hemagglutinin (HA) encapsulated in lipid nanoparticles (LNP) induce protective HA inhibition titers H10-specific CD4+ T cell responses after intramuscular or intradermal delivery rhesus macaques. Administration LNP/mRNA induced...
Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by are largely unknown. In this study, we demonstrate protective levels of antibodies hemagglutinin were induced after two immunizations modified non-replicating encoding influenza H10 encapsulated in lipid nanoparticles (LNP) non-human primates. While both intradermal...
Although intramuscular (i.m.) administration is the most commonly used route for licensed vaccines, subcutaneous (s.c.) delivery being explored several new vaccines under development. Here, we use rhesus macaques, physiologically relevant to humans, identify anatomical compartments and early immune processes engaged in response immunization via two routes. Administration of fluorescently labeled HIV-1 envelope glycoprotein trimers displayed on liposomes enables visualization targeted cells...
Cell fate decisions during early B cell activation determine the outcome of responses to pathogens and vaccines. We examined response T-dependent antigen in mice by single-cell RNA sequencing. Early after immunization, a homogeneous population activated precursors (APs) gave rise transient wave plasmablasts (PBs), followed day later emergence germinal center cells (GCBCs). Most APs rapidly exited cycle, giving non-GC-derived memory (eMBCs) that retained an AP-like transcriptional profile....
Licensed rabies virus vaccines based on whole inactivated are effective in humans. However, there is a lack of detailed investigations the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses lipid nanoparticle-formulated unmodified mRNA encoding glycoprotein (RABV-G) induces higher levels RABV-G specific plasmablasts T cells blood, plasma bone marrow compared to Rabipur non-human primates. The also generates binding...
Nanoparticles for multivalent display and delivery of vaccine antigens have emerged as a promising avenue enhancing B cell responses to protein subunit vaccines. Here, we evaluated in rhesus macaques immunized with prefusion-stabilized respiratory syncytial virus (RSV) F glycoprotein trimer compared nanoparticles displaying 10 or 20 copies the same antigen. We show that skews antibody specificities drives epitope-focusing responding cells. Antibody cloning repertoire sequencing revealed...
Abstract The immune responses to Novavax’s licensed NVX-CoV2373 nanoparticle Spike protein vaccine against SARS-CoV-2 remain incompletely understood. Here, we show in rhesus macaques that immunization with Matrix-M TM adjuvanted vaccines predominantly elicits events local tissues little spillover the periphery. A third dose of an updated based on Gamma (P.1) variant 7 months after two immunizations resulted significant enhancement anti-spike antibody titers and breadth including...
Transmission-blocking vaccines (TBVs) are considered an integral element of malaria eradication efforts. Despite promising evaluations Plasmodium falciparum Pfs25-based TBVs in mice, clinical trials have failed to induce robust and long-lived Ab titers, part due the poorly immunogenic nature Pfs25. Using nonhuman primates, we demonstrate that multiple aspects Pfs25 immunity were enhanced by antigen encapsulation poly(lactic-co-glycolic acid)–based [(PLGA)-based] synthetic vaccine particles...
Abstract Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand severity. cTfh frequencies correlate plasmablast SARS-CoV-2 antibody titers, avidity neutralization. Furthermore, but not other memory CD4...
BACKGROUND. The live attenuated BPZE1 vaccine candidate induces protection against B. pertussis and prevents nasal colonization in animal models. Here we report on the responses humans receiving a single intranasal administration of BPZE1.
Understanding the presence and durability of antibodies against SARS-CoV-2 in airways is required to provide insights into ability individuals neutralize virus locally prevent viral spread. Here, we longitudinally assessed both systemic airway immune responses upon infection a clinically well-characterized cohort 147 infected representing full spectrum COVID-19 severity, from asymptomatic fatal disease. In addition, evaluated how vaccination influenced antibody subset these during...
mRNA vaccines are likely to become widely used for the prevention of infectious diseases in future.Nevertheless, a notable gap exists mechanistic data, particularly concerning potential effects sequential immunization or preexisting immunity on early innate immune response triggered by vaccination.In this study, healthy adults, with without documented prior SARS-CoV-2 infection, were vaccinated BNT162b2/Comirnaty vaccine.Prior infection conferred significantly stronger induction...
Abstract Discrete protein assemblies ranging from hundreds of kilodaltons to megadaltons in size are a ubiquitous feature biological systems and perform highly specialized functions 1,2 . Despite remarkable recent progress accurately designing new self-assembling proteins, the complexity these has been limited by reliance on strict symmetry 3 Here, inspired pseudosymmetry observed bacterial microcompartments viral capsids, we developed hierarchical computational method for large...
Abstract Myeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses in several pathological conditions. Whether MDSCs increase and influence temporary inflammation, such as after vaccine administration, is unknown. Using the rhesus macaque model, which critical for late-stage testing, we demonstrate that monocytic (M)-MDSCs polymorphonuclear (PMN)-MDSCs can be detected using markers used humans. However, whereas M-MDSCs lacked expression CD33, PMN-MDSCs were identified...
Nonhuman primates have a key role in the evaluation of novel therapeutics including vaccine and drug development. Monitoring biochemical hematological parameters macaques is critical to understand toxicity safety, but general reference intervals following standardized guidelines remain be determined. Here we compiled multiple internal datasets define normal ranges classical Indian Chinese rhesus as well cynomolgus macaques. Furthermore, combination data with phenotypic information cells...
Abstract A single dose of the replication-competent, live-attenuated yellow fever virus (YFV) 17D vaccine provides lifelong immunity against human YFV infection. The magnitude, kinetics, and specificity B cell responses to are relatively less understood than T responses. In this clinical study, we focused on early immune events critical for development humoral vaccination in 24 study subjects. More specifically, studied dynamics several populations over time neutralizing Abs. At 7 d...
Abstract Understanding the presence and durability of antibodies against SARS-CoV-2 in airways is required to provide insights on ability individuals neutralize virus locally prevent viral spread. Here, we longitudinally assessed both systemic airway immune responses upon infection a clinically well-characterized cohort 147 infected representing full spectrum COVID-19 severity; from asymptomatic fatal disease. In addition, evaluated how vaccination influenced antibody subset these during...
Abstract Targeting CD40 by agonistic antibodies used as vaccine adjuvants or for cancer immunotherapy is a strategy to stimulate immune responses. The majority of studied anti-human require crosslinking their Fc region inhibitory FcγRIIb induce stimulation although this has been associated with toxicity in previous studies. Here we introduce an monoclonal IgG1 antibody (MAB273) unique its specificity the CD40L binding site but devoid Fcγ-receptor binding. We demonstrate rapid MAB273 B cells...