A5040104802- HIV Research and Treatment
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Malaria Research and Control
- Influenza Virus Research Studies
- Gene expression and cancer classification
- Viral gastroenteritis research and epidemiology
- Complement system in diseases
- Mosquito-borne diseases and control
- Immunotherapy and Immune Responses
- interferon and immune responses
- Salmonella and Campylobacter epidemiology
- Atherosclerosis and Cardiovascular Diseases
- Respiratory viral infections research
- Genetics, Bioinformatics, and Biomedical Research
- HIV/AIDS drug development and treatment
- Machine Learning and Data Classification
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- SARS-CoV-2 detection and testing
- Cardiovascular Conditions and Treatments
- Neonatal Respiratory Health Research
- Machine Learning in Bioinformatics
Duke University
2019-2025
International Vaccine Institute
2024
Durham VA Medical Center
2023
Center for Human Genetics
2023
Background: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, elicitation breadth antibody responses against V1V2 Env are important considerations for candidates. The region’s highly nature extensive diversity subtype C Envelopes (Envs) make response high priority regimens aiming V1V2-mediated protection Southern Africa. Here, we determined whether anti-V1V2 can be...
One approach for developing a more universal influenza vaccine is to elicit strong immune responses against canonically immunosubdominant epitopes in the surface exposed viral glycoproteins. While standard vaccines typically induce directed primarily mutable hemagglutinin (HA) head domain, there are generally limited or variable relatively conserved HA stalk domain and neuraminidase (NA) proteins. Here we describe that utilizes combination of wildtype (WT) virus particles along with...
Typhoid Vi vaccines have been shown to be efficacious in children living endemic regions; however, a widely accepted correlate of protection remains established. We applied systems serology approach identify Vi-specific serological correlates using samples obtained from participants enrolled an experimental controlled human infection study. Participants were vaccinated with Vi-tetanus toxoid conjugate (Vi-TT) or unconjugated Vi-polysaccharide (Vi-PS) and subsequently challenged Salmonella...
Vaccination against Salmonella Typhi using the Vi capsular polysaccharide, a T-cell independent antigen, can protect from development of typhoid fever. This implies that antibodies to alone in absence T cell-mediated immune response; however, protective have not been well characterized. We hypothesized variability biophysical properties vaccine-elicited antibodies, including subclass distribution and avidity, may impact outcomes. To interrogate relationship between antibody protection fever,...
Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of hemagglutinin (HA) glycoprotein. Because viral antigenic drift at these sites, need to be updated and readministered annually. To increase breadth vaccine-mediated protection, we developed an antigenically complex mixture recombinant HAs designed redirect immune more conserved domains protein. Vaccine-induced antibodies were disproportionally...
Authorization of the Matrix-M (MM)–adjuvanted R21 vaccine by three countries and its subsequent endorsement World Health Organization for malaria prevention in children are a milestone fight against malaria. Yet, our understanding innate adaptive immune responses elicited this remains limited. Here, we compared clinically relevant adjuvants [3M-052 + aluminum hydroxide (Alum) (3M), TLR7/8 agonist formulated Alum; GLA-LSQ, TLR4 liposomes with QS-21; MM, now-approved adjuvant R21] their...
Importance Preterm infants are recommended to receive most vaccinations at the same postnatal age as term infants. Studies have inconsistently observed an increased risk for postvaccination apnea in preterm Objective To compare proportions of hospitalized with and other adverse events 48 hours after 2-month vs no vaccinations. Design, Setting, Participants This randomized, open-label clinical trial took place 3 US neonatal intensive care units between August 2018 October 2021. Infants 6 12...
Abstract RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated efficacy up to 86.7% in controlled human infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates humoral mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays two CHMI studies varying RTS,S/AS01B dose timing regimens. Central...
Importance Limited randomized clinical trial data exist on the safety of simultaneous administration COVID-19 and influenza vaccines. Objective To compare reactogenicity, safety, changes in health-related quality life (HRQOL) after vs sequential receipt messenger RNA (mRNA) vaccine quadrivalent inactivated (IIV4). Design, Setting, Participants This randomized, placebo-controlled was conducted between October 8, 2021, June 14, 2023, at 3 US sites. were nonpregnant persons aged 5 years or...
Abstract In the RV144 trial, vaccine-induced V1V2 IgG correlated with decreased HIV-1 risk. We investigated circulating antibody specificities in two phase 1 poxvirus prime-protein boost clinical trials conducted South Africa: HVTN 097 (subtype B/E) and 100 C). With cross-subtype peptide microarrays multiplex binding assays, we probed magnitude breadth of responses to linear variable loop 2 (V2) conformational specificities. Antibodies targeting V2 epitope, a correlate risk RV144, were...
Data analysis and knowledge discovery has become more important in biology medicine with the increasing complexity of biological datasets, but necessarily sophisticated programming skills in-depth understanding algorithms needed pose barriers to most biologists clinicians perform such research. We have developed a modular open-source software, SIMON, facilitate application 180+ state-of-the-art machine-learning high-dimensional biomedical data. With an easy-to-use graphical user interface,...
RTS,S/AS01 (GSK) is the world’s first malaria vaccine. However, despite initial efficacy of almost 70% over 6 months follow-up, waned time. A deeper understanding immune features that contribute to RTS,S/AS01-mediated protection could be beneficial for further vaccine development. In two recent controlled human infection (CHMI) trials in malaria-naïve adults, MAL068 and MAL071, against patent parasitemia ranged from 44% 87% across studies arms (each study included a standard arm with three...
SUMMARY Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, now SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against betaCoVs circulating in animals have potential to prevent future betaCoV pandemics. Here, we show immunization of macaques with a multimeric receptor binding domain (RBD) nanoparticle adjuvanted 3M-052-Alum elicited cross-neutralizing antibody SARS-CoV-1, SARS-CoV-2,...
Diversity in specificity of polyclonal antibody (pAb) responses is extensively investigated vaccine efficacy or immunological evaluations, but the heterogeneity avidity rarely probed as convenient tools are lacking. Here we have developed a antibodies resolution tool (PAART) for use with label-free techniques, such surface plasmon resonance and biolayer interferometry, that can monitor pAb-antigen interactions real time to measure dissociation rate constant ( k d ) defining avidity. PAART...
Analyses of human clinical HIV-1 vaccine trials and preclinical studies performed in rhesus macaque (RM) models have identified associations between non-neutralizing Fc Receptor (FcR)-dependent antibody effector functions reduced risk infection. Specifically, antibody-dependent phagocytosis (ADP) has emerged as a common correlate infection multiple RM the HVTN505 trial. This recurrent finding suggests that responses with capability to mediate ADP are most likely desirable component aimed at...
The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates decreased infection risk. New strategies to increase magnitude and durability protective immunity are critically needed. RV305 clinical trial evaluated immunological impact a follow-up boost HIV-1-uninfected RV144 recipients after 6–8 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 or ALVAC-HIV + gp120)....
Abstract Background The malaria vaccine, RTS,S/AS01, demonstrated an enhanced efficacy (86.7%) in a delayed third fractional dose (0.1.7Fx) regimen controlled human infection trials compared with standard full-dose (0.1.2) (62.5%). To understand the humoral component of RTS,S/AS01 vaccine-induced protection against sporozoite these 2 regimens, we investigated serum antibody dynamics 0.1.2 and 0.1.7Fx groups vaccinees. Methods specific binding responses (magnitude) dissociation rates...
Adjuvants can alter the magnitude, characteristics, and persistence of humoral response to protein vaccination. HIV vaccination might benefit from tailored adjuvant choice as raising a durable protective has been exceptionally challenging. Analysis trials partially effective vaccines have identified features immune that correlate with decreased risk, including high titers V1V2-binding IgG IgG3 responses low IgA enhanced Fc effector functions, notably antibody-dependent cellular cytotoxicity...
BACKGROUNDThe mechanism(s) responsible for the efficacy of WHO-recommended malaria vaccine RTS,S/AS01 are not completely understood. We previously identified RTS,S vaccine-induced Plasmodium falciparum circumsporozoite protein-specific (PfCSP-specific) antibody measures associated with protection from controlled human infection (CHMI). Here, we tested protection-predicting capability these in independent CHMI studies.METHODSVaccine-induced total serum (immunoglobulins, Igs) and subclass...
Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth durability, it is desirable deliver both viral hemagglutinin neuraminidase glycoproteins. Delivering multiple antigens individually, however, complicates manufacturing increases cost, thus would be beneficial express proteins from a single mRNA. Here, we develop an mRNA genetic...
Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those humans. Here, we evaluated FcR-related functionality natural killer cells (NKs) from peripheral blood uninfected humans identify intra- inter-species variation. NKs were screened for FcγRIIIa (human) FcγRIII (RM) genotypes...
Broadly neutralizing antibodies (bNAbs), known to mediate immune control of HIV-1 infection, only develop in a small subset infected individuals. Despite being traditionally associated with patients high viral loads, bNAbs have also been observed therapy naïve HIV-1+ naturally controlling virus replication [Virus Controllers (VCs)]. Thus, dissecting the bNAb response VCs will provide key information about what constitutes an effective humoral natural infection. In this study, we identified...
Despite significant progress in vaccine research, the level of protection provided by vaccination can vary significantly across individuals. As a result, understanding immunologic variation individuals response to is important for developing next-generation efficacious vaccines. Accurate outcome prediction and identification predictive biomarkers would represent step towards this goal. Moreover, early phase clinical trials, small datasets are prevalent, raising need challenge building robust...