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Early Career Investigator Recognition

About the Early Career Investigator Recognition

To support the Global HIV Vaccine Enterprise’s efforts to raise the visibility and participation in the HIV vaccine field of Early Career Investigators, the CAVD has implemented a process to recognize the early career investigators who have made significant contributions to research conducted within the CAVD.

The development of an HIV vaccine is one of the most complicated biomedical challenges facing the world at this time and today’s early career investigators are needed to ensure that the field remains innovative and scientifically robust in order to meet the challenge of ending the HIV/AIDS epidemic.

Beginning in July 2009, each month the CAVD recognizes one to two early career investigators who are selected based on the following criteria:

  • Nominated by a CAVD Principal Investigator
  • Graduate student, Post-Doc, or Assistant Professor
  • Major contributor to a CAVD-related research publication, or a presenter of CAVD-related research at a major international meeting

 

November 2016

 

Slim Fourati, Ph.D.

Case Western Reserve University, US

In Dr. Fourati's online research forum, his presentation covered the HVTN505 trial tested the efficacy of a DNA prime–recombinant adenovirus 5 boost (DNA/rAd5) HIV vaccine in persons at an increased risk for HIV-1 infection in the United States. 2504 men were randomized to receive the vaccine or placebo and were assessed for HIV-1 acquisition up to 2 years. The DNA/rAd5 vaccine did not reduce the rate of HIV-1 acquisition compared to placebo. A retrospective study looking for markers of susceptibility to HIV-1 infection based on blood samples collected during the HVTN505 trial is ongoing. A multi-omics data analysis including RNA-sequencing (RNA-Seq), flow cytometry (FCM) and cytokine/chemokines levels assessment was conducted on those blood samples. Analysis of the FCM data using unsupervised (multidimensional scaling) and supervised (LASSO logistic regression) approaches revealed that an elevated activation status of immune cells prior to infection was associated to an increased risk of infection. RNA-Seq of sorted immune cells revealed the activation of the canonical interferon-gamma (IFNγ) signaling pathway in myeloid dendritic cells (mDCs), observed prior to immunization, was the best predictor of HIV-1 acquisition (ROC: AUC>0.701). An integrative analysis of the RNA-Seq expression and the FCM data revealed a positive correlation between activation of the IFNγ signaling pathway in mDCs and higher frequency of activated T-cells (projection-based integrative analysis). Higher expression of IFNγ signaling pathway in mDCs leading to an increase of activated effector immune cells prior to immunization was identified as a new correlate of HIV-1 acquisition. Current work is undergoing to identify activators of the IFNγ signaling pathway in mDCs.

June 2016

 

Bryan Briney, Ph.D.

The Scripps Research Institute, US

In Dr. Briney's online research forum, his presentation covered induction of broadly neutralizing antibodies (bnAbs) is a primary goal of HIV vaccine development. VRC01-class bnAbs are important vaccine leads because their precursor B cells targeted by an engineered priming immunogen are relatively common among humans. This priming immunogen has demonstrated the ability to initiate a bnAb response in animal models, but recall and maturation toward bnAb development has not been shown. Here, we report the development of boosting immunogens designed to guide the genetic and functional maturation of previously primed VRC01-class precursors. Boosting a transgenic mouse model expressing germline VRC01 heavy chains produced broad neutralization of near-native isolates (N276A) and weak neutralization of fully native HIV. Functional and genetic characteristics indicate that the boosted mAbs are consistent with partially mature VRC01-class antibodies and place them on a maturation trajectory that leads toward mature VRC01-class bnAbs. The results show how reductionist sequential immunization can guide maturation of HIV bnAb responses.​

June 2015

 

Marina Caskey, M.D.

Assistant Professor of Clinical Investigation, Laboratory of Molecular Virology, The Rockefeller University, US

In Dr. Caskey's online research forum, her presentation gave an overview of despite the major success of combination antiretroviral therapy (ART) in suppressing viral replication and preventing disease progression, HIV-1 infection persists and is not eliminated by available antiretroviral drugs. Moreover, an effective HIV vaccine is not yet available. Broadly neutralizing antibodies differ from other therapeutic modalities for HIV-1 infection in several respects. First, they can neutralize the pathogen directly; second, they have the potential to clear the virus and infected cells through engagement of innate effector responses; and third, immune complexes produced by the passively transferred antibodies may enhance immunity to HIV-1. In addition, since antibodies have far longer half-lives than currently used antiretroviral drugs, they might allow for more convenient prevention or therapeutic regimens. Therefore, broadly neutralizing antibodies are a promising modality to potentially prevent HIV-infection or as adjuncts to ART, in stand-alone maintenance treatment regimens or in strategies that aim to eradicate HIV-1 or to induce long-term ART-free HIV-1 remission. 3BNC117 and 10-1074 are two anti-HIV-1 broadly neutralizing antibodies that target the CD4 binding site and the base of the V3 loop within HIV-1 envelope gp-120, respectively. When tested against large HIV-1 pseudovirus panels 3BNC117 neutralizes more than 80% of the viral isolates and 10-1074 neutralizes between 60 and 70% at low concentrations. They were selected for clinical development for their in vitro neutralizing breadth and potency and for their antiretroviral activity in humanized mice (hu-mice) and non-human primate models (NHP). In humans, both 3BNC117 and 10-1074 were generally safe and well tolerated at doses up to 30 mg/kg. 3BNC117 and 10-1074 half-lives were approximately 2 weeks in HIV-uninfected and about 10 days in viremic HIV-infected individuals. Both 3BNC117 and 10-1074 induced rapid decreases in plasma HIV-1 RNA levels, with average decline in plasma viremia of approximately 1.5 log10 copies/ml. Selective pressure on circulating viruses was observed after administration of either 3BNC117 or 10-1074. Planned clinical studies will evaluate their safety, pharmacokinetics and antiviral activity when given in combination to HIV-infected or HIV-uninfected individuals.

May 2016

 

Wen-Han Yu, Ph.D.

post-doctoral fellow, Ragon Institute and Massachusetts Institute of Technology, US

In Dr. Yu's online research forum, his presentation gave an overview of beyond its role in immune evasion, the carbohydrate shield of the HIV viral envelope serves as a critical antigenic determinant for many broadly neutralizing antibodies (bNAbs). Rapid viral evolution linked to the simple deletion/addition of N-glycan sites likely results not only in rapid epitope changes, but also in topograp​hical remodeling of the antigenicity of the whole viral envelope glyco-protein. We will present a synthetic biology approach that aims to take advantage of the imperfect glycosylation of recombinant gp120 proteins, to remodel the glycome of HIV envelope and to engineer the glycome to selectively enhance the antigenicity of the HIV envelope. Specifically, we reverse-engineered the N-glycoproteome heterogeneity using 94 HIV recombinant gp120s, and linked these to bNAb binding fingerprints, thereby identifying the glycan site determinants that coordinately shape the epitope topography. Glycans were classified as antagonists or agonists of bNAb binding, and the steric impacts to gp120 protein were estimated. Taking these design principles, a novel class of immunogens were generated that not only exhibited enhanced binding to glycan-dependent bNAbs, but having selectively engineered antigenicity to one glycan-dependent bNAb and not another. This approach then provides a different rational design strategy to improve recombinant HIV envelope antigenicity, for gp120, trimers, or native-structures, particularly to glycan-dependent bNAbs, via alteration of global envelop glycosylation profiles.​

April 2016

 

Drienna Holman

Program Manager – Special Projects; Vaccine Immunology Statistical Center (VISC), Fred Hutchinson
Cancer Research Center, US

In Ms. Holman's online research forum, her presentation covered the CAVD DataSpace is a data sharing and discovery tool for self-service exploration of data and information from CAVD studies, helping members to better understand and expand upon the work being done within their research community. This online forum is an introductory session to show you how the DataSpace can benefit and enhance the work at your consortia. In this session, we will show you how to explore information from over 225 CAVD studies, including information about the assays, products, and designs used in the studies. We’ll also explore harmonized, integrated data from clinical and NHP studies for 4 assays – NAb, ICS, BAMA, and IFN-γ ELISpot. Several new updates have been added to the DataSpace since our launch in December! We'll highlight some of those new capabilities and tell you about other enhancements we've got planned.​​

March 2016

 

Simone Richardson, M.S.

National Institute for Communicable Diseases and the University of Witwatersrand; Johannesburg, ZA

In Ms. Richardson's online research forum, her presentation covered the finding that antibody-dependent cell-mediated cytotoxicity (ADCC) was a correlate of protection in the RV144 HIV-1 vaccine trial has suggested that an effective HIV vaccine should elicit antibodies with both neutralizing and Fc effector functions. However, it is unknown if individuals who develop broadly cross-neutralizing antibodies (bNAbs) also have antibodies with increased Fc effector polyfunctionality. Here, we present a comparative study of the HIV-specific Fc effector function, isotype usage and glycan selection in IgG isolated from individuals that develop bNAbs and those that do not. We demonstrate the relationships between neutralization breadth and extra-neutralizing functions and preferential isotype usage and epitope target over the course of infection. Ultimately, investigating the link between the Fab and Fc portion of the antibody and its evolution over time will allow us to determine how tuneable Fc effector functions are in the context of bNAb development.

 

 

2016 Early Career Investigators

To view the honorees that occured in 2016, click the following link: 2016 Early Career Investigators

2015 Early Career Investigators

To view the honorees that occured in 2015, click the following link: 2015 Early Career Investigators

2014 Early Career Investigators

To view the honorees that occured in 2014, click the following link: 2014 Early Career Investigators

2013 Early Career Investigators

To view the honorees that occured in 2013, click the following link: 2013 Early Career Investigators

2012 Early Career Investigators

To view the honorees that occured in 2012, click the following link: 2012 Early Career Investigators

2011 Early Career Investigators

To view the honorees that occured in 2011, click the following link: 2011 Early Career Investigators

2010 Early Career Investigators

To view the honorees that occured in 2010, click the following link: 2010 Early Career Investigators

2009 Early Career Investigators

To view the honorees that occured in 2009, click the following link: 2009 Early Career Investigators

 
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