Papers by Francois Villinger
bioRxiv (Cold Spring Harbor Laboratory), May 19, 2022
bioRxiv (Cold Spring Harbor Laboratory), May 15, 2021
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms
Research Square (Research Square), Nov 29, 2022
The Journal of Immunology
Epstein-Barr virus (EBV) is a gamma-Herpesvirus associated with lymphoma or nasopharyngeal carcin... more Epstein-Barr virus (EBV) is a gamma-Herpesvirus associated with lymphoma or nasopharyngeal carcinoma in immunocompromised patients. Lymphocryptovirus (LCV) infection of rhesus macaques replicates several characteristics of the human EBV infection. EBNA-1 is a nuclear virus protein expressed in all phases of EBV/LCV infections, essential for survival, malignant transformation, tumor progression and escape from host immune response. In spite of its importance for viral replication and survival, EBNA-1 is poorly immunogenic during lytic or latent infection. However, since protection against select experimental infections was achieved after enhancement of antigen immunogenicity through immunization, we hypothesized that eliciting EBNA-1-specific responses during chronic latent infection could increase control of EBV/LCV in vivo. We therefore attempted to enhance and broaden LCV EBNA-1 responses via immunization with an AdC68-LCV-EBNA-1 vector in groups of rhesus macaques that were laten...
Journal of physics, Oct 1, 2022
International Journal of Environmental Research and Public Health
Our lab investigates the anti-HIV-1 activity in Momordica balsamina (M. balsamina) leaf extract. ... more Our lab investigates the anti-HIV-1 activity in Momordica balsamina (M. balsamina) leaf extract. Traditional Senegalese healers have used M. balsamina leaf extract as a part of a plant-based treatment for HIV/AIDS infections. Our overall goal is to define and validate the scientific basis for using M. balsamina leaf extract as a part of the traditional Senegalese treatment. As an initial characterization of this extract, we used activity-guided fractionation to determine the active ingredient’s solubility and relative size. We found that M. balsamina leaf extract inhibits HIV-1 infection by >50% at concentrations of 0.02 mg/mL and above and is not toxic over its inhibitory range (0–0.5 mg/mL). We observed significantly more antiviral activity in direct water and acetonitrile extractions (p ≤ 0.05). We also observed significantly more antiviral activity in the aqueous phases of ethyl acetate, chloroform, and diethyl ether extractions (p ≤ 0.05). Though most of the antiviral activi...
The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains ... more The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 i...
Science, 1996
The administration of antigens in soluble form can induce antigen-specific immune tolerance and s... more The administration of antigens in soluble form can induce antigen-specific immune tolerance and suppress experimental autoimmune diseases. In a marmoset model of multiple sclerosis induced by myelin oligodendrocyte glycoprotein (MOG), marmosets tolerized to MOG were protected against acute disease, but after tolerization treatment a lethal demyelinating disorder emerged. In these animals, MOG-specific T cell proliferative responses were transiently suppressed, cytokine production was shifted from a T helper type 1 (TH1) to a TH2 pattern, and titers of autoantibodies to MOG were enhanced. Thus, immune deviation can increase concentrations of pathogenic autoantibodies and in some circumstances exacerbate autoimmune disease.
Emerging Infectious Diseases, 2000
Annals of Tropical Medicine And Parasitology, 1998
Retrovirology, Sep 1, 2012
The Journal of Immunology
A study was performed to identify, characterize and compare the level and function of peripheral ... more A study was performed to identify, characterize and compare the level and function of peripheral Tregs in uninfected and SIV-infected rhesus macaques (RM) and sooty mangabeys (SM) to determine if Tregs contribute to the muted immune response that is evident in SIV-infected disease-resistant SM but readily detectable in SIV-infected disease-susceptible RM. Results show that SIV-infected SM maintain the level and function of Tregs but a substantial decline was noted in RM. A strong correlation between plasma VL and the level of Tregs was observed in SIV-infected RM but not SM. RM VL controllers exhibited lower levels of immune activation and recovered pre-infection levels of Tregs that were fully functional when tested for suppressive activity in vitro. ICC assays showed that Treg-depleted PBMC fractions from RM but not SM exhibit increased CD4+ and CD8+ T-cell responses to select SIV peptide pools suggesting that Tregs play a role in the SIV-specific immune response at least in RM. T...
The Journal of Immunology
Natural Killer (NK) cells play an essential role in antiviral immunity, however knowledge pertain... more Natural Killer (NK) cells play an essential role in antiviral immunity, however knowledge pertaining to their function in lymphoid organs during chronic HIV infection is not clearly elucidated. Lymph node (LN) follicles constitute major reservoir sites for HIV persistence. Cure strategies could benefit from the LN CXCR5+ NK cells able to access/eliminate viral reservoirs. Here we studied the phenotype, distribution and function of CXCR5+ NK cells in the LN of SHIV naive and chronic SHIV-infected (>14 weeks PI) rhesus macaques (RM) and its association with plasma viral RNA levels. We found that prior to infection, a significant proportion of NK cells (~15%) expressed CXCR5. Following infection, the frequency of CXCR5+ NK cells was significantly higher in chronic SHIV-infected RM. Phenotypically CXCR5+ NK cells express higher levels of CD32a and CD16 compared to CXCR5− cells, which might be important for ADCC function. RNA expression profiling of sorted CXCR5+ and CXCR5− NK cells f...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to ... more The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOC) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOC. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses against VOC, as compared to non-human primates or humans, suggesting caution should be exercised when interpreting data for this animal model.
Science Immunology, 2020
Our study describes robust and durable induction of HIV-1–specific antibody as well as germinal c... more Our study describes robust and durable induction of HIV-1–specific antibody as well as germinal center and plasma cellular responses in rhesus macaques.
Journal of Medical Primatology, 1990
Initial studies have revealed subtle differences in the T cell proliferative response to whole SI... more Initial studies have revealed subtle differences in the T cell proliferative response to whole SIV antigen in the peripheral blood mononuclear cells (PBMC) from sooty mangabeys and rhesus macaques. Preliminary findings utilizing the cellular Western blot assay are described.
Blood, 2019
Introduction: Current therapies for multiple myeloma (MM), such as immunomodulatory agents, prote... more Introduction: Current therapies for multiple myeloma (MM), such as immunomodulatory agents, proteasome inhibitors, stem-cell transplantation, and monoclonal antibodies against tumor-associated antigens have greatly improved patient survival. However, MM remains an incurable disease as most patients will eventually relapse. Recent advances in targeted T-cell therapies have shown promise in clinical trials but the adaptive immune system may be insufficient to eradicate all MM clones. In contrast, treatments harnessing the innate immune system have been relatively underdeveloped in MM despite evidence suggesting a role of innate immunity in the efficacy of existing therapies. Innate or innate-like cells, such as NK and γδ T cells, have the potential to display strong anti-tumor activity, and strategies aimed to improve or re-direct their cytotoxicity represent a new opportunity for cancer immunotherapies and a complementary approach to existing therapies. Here we describe the preclinic...
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Papers by Francois Villinger