A5002663565- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- HIV/AIDS Research and Interventions
- Parvovirus B19 Infection Studies
- Virus-based gene therapy research
- Organ Transplantation Techniques and Outcomes
- Immunodeficiency and Autoimmune Disorders
- Infant Nutrition and Health
- Liver Disease and Transplantation
- Blood groups and transfusion
- Virology and Viral Diseases
- Poxvirus research and outbreaks
- CAR-T cell therapy research
- Hepatitis B Virus Studies
- SARS-CoV-2 and COVID-19 Research
- HIV-related health complications and treatments
- Parasites and Host Interactions
- Transplantation: Methods and Outcomes
Duke Medical Center
2016-2025
Duke University
2016-2025
Center for Human Genetics
2023
Duke University Hospital
2013-2022
Uganda Virus Research Institute
2022
Makerere University
2022
Eurovacc Foundation
2022
University Teaching Hospital
2022
International Vaccine Institute
2022
University of North Carolina at Chapel Hill
2015
Analysis of correlates risk infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas Env-specific IgA responses directly risk. In secondary analysis, antibody-dependent cellular cytotoxicity (ADCC) was another inverse correlate but only presence low antibodies. Thus, we investigated hypothesis could attenuate protective effect through competition for same Env binding sites. We...
The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. secondary immune correlate analysis demonstrated that the combination low plasma anti-HIV-1 Env IgA antibodies and high levels antibody-dependent cellular cytotoxicity (ADCC) inversely with infection risk. One hypothesis is observed protection in partially due to ADCC-mediating antibodies. We found majority (73 90%) a representative group vaccinees displayed ADCC activity, usually (96.2%) blocked by...
ABSTRACT Among nonneutralizing HIV-1 envelope antibodies (Abs), those capable of mediating antibody-dependent cellular cytotoxicity (ADCC) activity have been postulated to be important for control infection. ADCC-mediating Ab must recognize antigens expressed on the membrane infected cells and bind Fcγ receptor (FcR) effector cell population. However, precise targets serum ADCC antibody are poorly characterized. The human monoclonal (MAb) A32 is a isolated from an chronically person. We...
Microbiota can mislead antibodies Unlike the response to many viral infections, most people do not produce capable of clearing HIV-1. Non-neutralizing that target HIV-1's envelope glycoprotein (Env) typically dominate response, which is generated by B cells cross-react with Env and intestinal microbiota. Williams et al. analyzed samples from individuals who had received a vaccine containing protein, including gp41 subunit. Most were non-neutralizing targeted gp41. The also reacted...
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.
Abstract We have developed a high‐throughput platform to detect the presence of HIV‐1 and SIV‐specific ADCC‐mediating antibody responses. The assay is based on hydrolysis cell‐permeable fluorogenic peptide substrate containing sequence recognized by serine protease, Granzyme B (GzB). GzB delivered into target cells cytotoxic effector as result antigen (Ag)‐specific Ab‐Fcγ receptor interactions. Within cells, cell‐derived hydrolyzes substrate, generating fluorescent signal that allows...
ABSTRACT The RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site immune pressure in the envelope (Env) variable region 2 (V2) focused on residue 169, which is included epitope recognized by vaccinee-derived V2 monoclonal antibodies. induced antibody-dependent cellular cytotoxicity (ADCC) against Env and constant 1 (C1) regions. In presence low IgA antibody levels, plasma levels ADCC activity...
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...
HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of that most likely protective, they not induced current vaccine candidates. In contrast, do neutralize primary strains in TZM-bl infection assay readily by candidates and have also been implicated as secondary correlates decreased risk RV144 efficacy trial. Here, we studied capacity anti-Env...
Abstract The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and gp120 subtype B/subtype E (B/E) proteins demonstrated 31% efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E to increase the diversity motifs in immunogen elicit a broader antibody response enhance protection. We find that immunization rhesus macaques with pentavalent results protection 55% pentavalent-vaccine-immunized from simian–human immunodeficiency virus (SHIV) challenge. Systems serology responses...
Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed improve T cell-mediated clearance HIV-1-infected cells. Specifically, employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm was derived from broadly binding,...
Current efforts toward human immunodeficiency virus (HIV) eradication include approaches to augment immune recognition and elimination of persistently infected cells following latency reversal. Natural killer (NK) cells, the main effectors innate system, recognize clear targets using different mechanisms than CD8+ T offering an alternative or complementary approach for HIV clearance strategies. We assessed impact interleukin 15 (IL-15) treatment on NK cell function potential stimulated...
Brain death that occurs in the setting of deceased organ donation for transplantation is associated with systemic inflammation unknown origin. It has recently been recognized mitochondria-derived damage-associated molecular patterns (mtDAMPs) released into circulation trauma and tissue injury are a inflammatory response. We examined blood donors found elevated levels cytokines chemokines correlated mtDAMPs. also donor neutrophils activated plasma contains neutrophil-activating factor blocked...
Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed specific receptor-binding domain (RBD) based rhesus macaques. We formulated RBD immunogen alum, licensed an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted promoted better binding effector...
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...
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...
The role of Antibody-dependent cellular cytotoxicity (ADCC) responses in HIV-1 controllers is still unclear due to the heterogeneity these patients. We analyzed 67 and found significantly higher levels ADCC antibodies versus viremic subjects (p = 0.017). Moreover, multivariate analysis revealed titers HLA B57- compared HLA-B57+ ones 0.0086). These data suggest a for immune control HIV, especially B57 negative controllers.
Most antibodies that broadly neutralize HIV-1 are highly somatically mutated in antibody clonal lineages persist over time. Here, we describe the analysis of human induced during an vaccine trial (GSK PRO HIV-002) used clade B envelope (Env) gp120 clone W6.1D (gp120(W6.1D)). Using dual-color antigen-specific sorting, isolated Env-specific monoclonal (MAbs) and studied persistence setting Env vaccination. We found evidence V(H) somatic mutation by but only to a modest level (3.8% ± 0.5%;...
Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing need for additional interventions to eliminate pediatric infections. Here, we aimed define humoral immune correlates risk mother-to-child transmission (MTCT) HIV-1, including responses associated protection in RV144 vaccine trial. Eighty-three untreated, HIV-1–transmitting mothers and 165 propensity score–matched nontransmitting were selected from Women...
Human cytomegalovirus (HCMV) is the most common infectious cause of infant birth defects, resulting in permanent neurological disability for one newborn child every hour United States. After more than a half century research and development, we remain without clinically licensed vaccine or immunotherapeutic to reduce burden HCMV-associated disease. In this study, sought improve upon glycoprotein B protein (gB/MF59), efficacious HCMV evaluated clinical trial, via targeted modifications either...
Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract postnatally, even absence maternal antiretroviral therapy. This suggests that immune factors breast milk help limit vertical transmission. We compared envelope-specific plasma antibody responses clade C postnatally transmitting nontransmitting control arm Malawi-based...
Infant responses to vaccines can be impeded by maternal antibodies and immune system immaturity. It is therefore unclear whether human immunodeficiency virus type 1 (HIV-1) vaccination would elicit similar in adults infants.HIV-1 Env-specific antibody were evaluated 2 completed pediatric vaccine trials. In the Pediatric AIDS Clinical Trials Group (PACTG) 230 protocol, infants vaccinated with 4 doses of Chiron rgp120 MF59 (n=48), VaxGen aluminum hydroxide (alum; n=49), or placebo (n=19)...