CFAR at Emory Newly Established Scientific Working Groups Leadership Announcement

CFAR at Emory Newly Established Scientific Working Groups Leadership Announcement

Health Equity Scientific Working Group

The central purpose of the Health Equity Scientific Working Group (SWG) is to expand NIH-funded community-engaged research to promote health equity at Emory in collaboration with Morehouse School of Medicine (SOM) and community stakeholders in the Atlanta area. Activities will include hosting research proposal feedback sessions, quarterly seminars, networking events, and/or career development sessions as opportunities for CFAR Members, Morehouse faculty, and community partners to interact; and pilot test several mentoring mechanisms focused on developing underrepresented minority investigators.

Rhonda Conerly Holliday, PhD, MA
Co‐Director, Health Equity SWG
Dr. Holliday (Rhonda) is an Associate Professor of Community Health and Preventive Medicine at the Morehouse School of Medicine. She is a public health researcher with a background in developmental psychology. Rhonda has extensive expertise in Community Based Participatory Research (CPBR), health equity, and health communications. Her topical areas of interest include HIV prevention among adolescents and emerging adults, including college students and justice-involved individuals. She is the PI for the core research project for the Morehouse School of Medicine Prevention Research Center (U48DP006411), focusing on implementing a CBPR approach to HIV prevention on the campuses of HBCUs and Minority Serving Institutions. Importantly for this SWG, she has published not only on the results of her CBPR projects, but also on the methods and lessons learned in developing and executing community-academic partnerships.

Sophia Hussen, MD, MPH
Co‐Director, Health Equity SWG
Dr. Hussen (Sophia) is an Associate Professor of Global Health in the Rollins School of Public Health at Emory University with a joint appointment in the Division of Infectious Diseases in the Emory University School of Medicine. Sophia is an infectious diseases physician and public health scientist who conducts research related to improving HIV and mental health outcomes for youth living with HIV, with a particular focus on young Black gay and bisexual men. She has recently completed a CDC-funded pilot trial of a CBPR-developed intervention to enhance social capital among young Black gay and bisexual men living with HIV, and she is also incorporating participatory methodologies into ongoing NIH-funded intervention development grants (R34MH124638; R34 MH116805) and exploratory mixed methods work (R21MH121164). Sophia also leads community engagement efforts within the Emory Clinical Trials Unit (CTU) and the Atlanta site of the MACS/WIHS CCS.

Alphonso Mills, BA
Co‐Director, Health Equity SWG
Mr. Mills (Alphonso) is a community health worker at Positive Impact Health Centers (PIHC), a large Atlanta community-based organization focusing on infectious diseases care, mental health care, substance use treatment, and other support services for people living with and at risk for HIV. Alphonso, who is openly living with HIV, has developed a strong track record of both professional and personal advocacy in the local Atlanta community. He is a 2020 graduate of Morehouse College, where he majored in psychology. He has also served on a Community Advisory Board for several of Dr. Hussen’s research projects since 2017. Due to the sum of his professional, research-related, and personal experiences over the last five years, Alphonso has extensive community connections with key organizations and individuals working in the HIV field in Atlanta. He also has experience with CBPR and other research as a participant, research assistant, and advisor.

Next Generation Therapeutics Scientific Working Group

The Next Generation Therapeutics Scientific Working Group (SWG) seeks to catalyze opportunities for team science within and across Emory CFAR institutions to set the foundation for future exploration and development of (i) novel approaches for viral suppression in people living with HIV using combinations of therapeutics that overcome drug resistance associated with current ART and are delivered as formulations designed to facilitate their long-term release; and (ii) immune-based strategies, focusing on those FDA-approved for other diseases, aimed at targeting and limiting HIV residual disease and HIV reservoirs. Activities will include hosting research proposal feedback sessions, educational, networking events, and/or career development sessions as opportunities for CFAR Members, CDC staff, and Georgia Tech and Morehouse School of Medicine faculty to interact; provide structured mentoring for Early-Stage Investigators in the field to ensure a robust scientific future; and promote multi-investigator applications to the CFAR Developmental Core and ultimately to the NIH.

Stefan G. Sarafianos, PhD
Co‐Director, Next Generation Therapeutics SWG
Dr. Sarafianos (Stefan) is the Nahmias-Schinazi Chair, Professor, and Associate Director of the Laboratory of Biochemical Pharmacology (LOBP) Division in the Department of Pediatrics at Emory. He studies viral replication at the molecular level, its inhibition, drug resistance, and the development of drugs that will treat human disease by novel mechanisms of action. Stefan has worked in retroviral structural biology, biochemistry, and virology since 1993 and has published more than 170 manuscripts. In early biochemical work he identified the HIV reverse transcriptase (RT) active site residues that are involved in dNTP, DNA, and PPi binding prior to any crystallographic information. His lab has had extensive contributions in the development of potent inhibitors that act by novel mechanisms of action including EFdA (islatravir), currently in Phase III clinical trials (for which he was recently awarded an NIH MERIT award) and in characterizing their mechanisms of inhibition and resistance. Stefan has worked in the HIV capsid field for several years now, and his lab was the first to solve the elusive crystal structure of the native (uncrosslinked) hexameric HIV capsid protein (CA) in apo form and in complex with CA-targeting antiviral PF74 (Science, 2015). This set of structures provided the framework for studies in which 45 crystal structures of the native CA hexamer were solved with mutations that affect capsid stability, and in complexes with host factor peptides and CA-targeting antivirals. Extensive biophysical and virological characterization revealed compounds with proprietary compounds that improved potency, resistance profiles, and metabolic stability compared to PF74. Some compounds can inhibit clinically-relevant PF74- and GS-6207-resistant HIV-1 strains.

Mirko Paiardini, PhD
Co-Director, Next Generation Therapeutics SWG
Dr. Paiardini (Mirko) is an Associate Professor of Pathology and Laboratory Medicine at Emory and a Researcher at Yerkes National Primate Research Center and the Emory Vaccine Center. For almost 20 years, Mirko has been involved in studies of AIDS pathogenesis in both HIV-infected individuals and in the models of SIV infection in rhesus macaques (RMs). Mirko gained extensive experience with in vivo studies of SIV infection of RMs in which virus replication is suppressed by a potent ART regimen, thus validating this model for studies of HIV cure. He led several studies in which in vivo immune interventions have been conducted in ART-suppressed SIV-infected RMs, aimed at reducing, and possibly eliminating, immune dysfunctions and HIV persistence in people living with HIV, including treatment with IL-21, IL-15 agonist, fingolimod, as well as blockade of PD-1, CTLA-4, and IL-10. More recently, his laboratory developed the NHP model of SARS-CoV-2 infection to test the therapeutic potential of baricitinib. He directs several NIH-funded studies of HIV immunology, pathogenesis, and persistence. He is the principal investigator of ERASE (Enterprise for Research and Advocacy to Stop and Eradicate) HIV, which is an NIH-funded international collaboratory aimed at developing therapeutic interventions to cure HIV infection.

Susan Pereira Ribeiro, PhD
Associate Director, Next Generation Therapeutics SWG
Dr. Ribeiro (Susan) is an Assistant Professor of Translational Medicine in the Department of Pathology at Emory University. She is an immunologist with experience in multi-omics approaches and with expertise in the development of cellular and immune assays and sophisticated flow cytometry models. Susan has focused in pathogenesis, progression and responses to immune therapy in order to discriminate mechanisms that leads to different outcomes in different individuals (Ex. Responders and Non-responders to immune therapy). She has experience with the cellular and molecular aspects of HIV immune pathogenesis and immunotherapies, focused on HIV reservoir evaluation, immune-phenotyping, and also vaccine development/response assessment, and in vitro efficacy of HIV-CAR T cells. Most recently her research has focused on understanding the mechanisms of HIV reservoir maintenance and the absence of CD4 T cell recovery in HIV infected subjects that show different clinical outcomes .

James Kohler, PhD
Associate Director, Next Generation Therapeutics SWG
Dr. Kohler (James) is an Assistant Professor Laboratory of Biochemical Pharmacology Division in the Department of Pediatrics at Emory. James has expertise in mucosal immunology, mouse transgenic models, pathogenesis (cardiac and renal) and toxicity models for HIV and antiviral therapies for human viral infections. His past training and research experience have included development and use of murine models to measure induction of mucosal immunity, signal transduction pathways associated in immune targets of HIV-1, tissue-specific antiretroviral toxicity, and HIV-1 cell-tropism and mutagenesis. James provides mentorship and co-leads the HIV Division of the Laboratory of Biochemical Pharmacology (Schinazi Lab). He previously served as Associate Director of the Emory CFAR HIV Cure SWG, now the HIV Cure Research Cluster.

TRAINING OPPORTUNITY: NIH T32 Openings for  Post-Doctoral Fellows at Emory University Emory Training Program in HIV Translational Research to End the Epidemic

TRAINING OPPORTUNITY: NIH T32 Openings for Post-Doctoral Fellows at Emory University Emory Training Program in HIV Translational Research to End the Epidemic

Fellow-driven & mentor-supported HIV transla tional research fellowships starting Jan 1, 2022

Are you a PhD, MD, MD/PhD graduate with an int erest in HIV Translational Research? Are you within seven years of your terminal degree? Are y ou a U.S. Citizen or Naturalized (Green Card) U.S. Citizen? Can you devote two years to training?

All trainees must commit full-time effort to th e program and its related research activities.

Eligible Areas of HIV Research

  • Laboratory-based science, vaccine, and cure research
  • Patient-centered clinical research
  • Public health and implementation science

Trainees will gain expertise in cross-cutting areas ofscience and translation to the Ending the HIV Epidemic Initiative

HIV T32 Program Trainees will Receive:

  • Annual stipend at appropriate NIH-specifiedlevel based on years of postdoc experience
  • Travel & childcare allotments; research supplies
  • Tuition support for formal didactic training intranslational research (MSCR, CPTR, or selectedgraduate level courses)
  • Hands-on translational research rotation

DEADLINE FOR SUBMISSION: November 30, 2021
Application Process:

1.  Applicants should identify a potential mentor from the list below arranged by focus area. Applicants mustcontact the potential mentor to see if the mentor is accepting new fellows through the Emory HIV T32 program.Applicants should include their CV and a brief description of the area of mutual interest.

2.  Potential candidates should complete an HIV T32 Interest Form to initiate discussion with the faculty ProgramDirector (PD) in the target area of interest regarding the candidate application: https://bit.ly/EmoryHIVT32
a. Laboratory-based basic science, vaccine, and cure research: Ann Chahroudi, MD, PhD
b .Patient-centered clinical research: Colleen Kelley, MD, MPH
c. Public health and implementation science: Patrick Sullivan, DVM, PhD

3.  Approval to apply must be obtained prior to November 15, 2021. Candidates are encouraged to apply aftermentor and program reviews are complete and approval is given.

To apply, submit an application package including the following documents as a single PDF via email to cfaradmin@emory.edu by 5 PM EST on November 30, 2021:

  • Cover letter specifying focus area of interest with statement of future goals for a career in HIV research. Applicantshould include personal qualifications for the fellowship and what they hope to gain from the fellowship;
  • Current CV or NIH biosketch;
  • A letter of support from the proposed HIV T32 mentor;
  • Letter(s) of support from one other scientist (e.g. recent supervisor, mentor, or a collaborator);
  • A two-page description of the proposed research project and proposed didactic training plan (includinggraphs/figures but not references);
  • MD applicants from clinical departments must also provide a letter from the applicant’s Department/DivisionChair, indicating departmental commitment to provide at least 75% protected time for the trainee applicant todevote to the proposed research project. This letter can be same as the required letter of support from one otherscientist, described above.
Lessons from 40 years of HIV/AIDS

Lessons from 40 years of HIV/AIDS

Featured article in Emory Report
By Martha McKenzie | Emory Report | June 1, 2021

Forty years ago, on June 5, 1981, the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (MMWR) carried a report of five otherwise healthy gay men in Los Angeles who suffered from a rare form of pneumonia. Two had died.

James Curran, an epidemiologist in the CDC’s Sexually Transmitted Disease Control Division at the time, was asked to review the report before it was published. That was his first glimpse at the disease that would roil the world and define his career: acquired immunodeficiency syndrome (AIDS).

Soon after the report was published, Curran, now dean of Emory University’s Rollins School of Public Health, was asked to chair a task force organized to investigate the cause of this unusual outbreak. He was detailed to the investigative team for 90 days. The assignment lasted 15 years.

The task force’s first order of business was to establish a case definition, determine how the disease spread, and develop prevention recommendations.

“In those early days it was all boots-on-the-ground surveillance,” says Curran. “We tried to identify and follow everyone who fit the description, which soon included other opportunistic infections and a rare cancer called Kaposi’s sarcoma in addition to Pneumocystis pneumonia. We were trying to answer questions like, did these cases only occur in gay men? Were they limited to California and New York? Were they always fatal?”

Within weeks, Curran’s team confirmed more than 25 additional cases. The case definition the team put together based on their discoveries was adopted worldwide, allowing early and consistent recognition of the global AIDS epidemic.

It took two years for the cause of AIDS — a novel retrovirus eventually named human immunodeficiency virus (HIV) — to be identified.

Since then, vast progress has been made in diagnosis, prevention and treatment. Drugs developed at Emory — Emtriva and Epivir — are among the most widely used to suppress viral loads in infected people. The development of pre-exposure prophylaxis (PrEP) offered HIV-negative people effective protection from contracting the virus. Over the decades, AIDS went from being a death sentence to a chronic, life-long condition that could be managed with the correct medications.

In 1995 Curran left the CDC to become the dean of the Rollins School of Health, but he continued working in AIDS as co-director of the Emory Center for AIDS Research (CFAR). On the 40th anniversary of the first published account of AIDS, he reflects on the progress that has been made and what lies ahead.

“We’ve come so very far, yet there are about 38 million people worldwide living with HIV,” says Curran. “It’s a silent disease, so there are many more than 100,000 people in the U.S. who are infected but don’t know it. We’ve been able to reduce mortality and slow the transmission rate, but current therapy is not curative and must be continued for life. We can’t talk about totally eliminating AIDS until we’ve developed a vaccine and curative therapy. These remain important priorities for our current CFAR scientists.”

Still, the history of AIDS offers positive lessons. Though the beginning of epidemic was characterized by fear and homophobia, with President Ronald Reagan refusing to speak publicly about AIDS for nearly six years, a commitment to fight the disease prevailed. The George W. Bush administration established the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) to bring relief, including heavily discounted drugs, to Africa and Asia, which suffered disproportionately.

“That global philanthropic commitment has saved tens of millions of lives,” says Curran.

Governments would do well to heed this lesson, especially in the face of wealthier nations hoarding COVID-19 vaccines.

“One thing AIDS taught us, and subsequently Ebola and Zika: Pathogens do not respect national boundaries,” says Curran. “If we want to keep ourselves safe, we have to keep everyone safe.”

Soon after the CDC reported the first cases of what would come to be known as AIDS, epidemiologist James Curran, shown here at the CDC in 1985, was asked to chair a task force to investigate the cause. Curran became dean of Emory’s Rollins School of Public Health in 1995. Photo by Steve Ringman/San Francisco Chronicle via Getty Images.

Emory-developed COVID-19 vaccine safe, effective in animal models

Emory-developed COVID-19 vaccine safe, effective in animal models

Featured article in Emory Report
By Lisa Newbern | Woodruff Health Sciences Center | February 4, 2021

Researchers at Yerkes National Primate Research Center and Emory Vaccine Center have developed a COVID-19 vaccine that has proven safe and effective in mice and monkeys. The results were published online Thursday, Feb. 4 in Immunity.

The Emory COVID-19 vaccine induces protective immunity via the platform of modified vaccinia Ankara (MVA), a harmless version of a poxvirus that is well-known for its use in HIV/AIDS vaccines. Like the Moderna and Pfizer vaccines, the MVA COVID-19 vaccine induces strong neutralizing antibodies, which support the immune system’s ability to fight infections. The MVA COVID-19 vaccine also induces killer CD8 T cells, providing a multi-pronged approach to halting SARS-CoV-2.

In addition, Emory researchers say the vaccine is easily adaptable to address disease variants and can be used in combination with existing vaccines to improve their ability to combat variants and has the potential to be equally effective with a single dose.

Lead researcher Rama Amara, PhD, built the MVA COVID-19 vaccine based on his more than 20 years of experience working with MVA and animal models to develop an HIV/AIDS vaccine. He and his Yerkes-based research team tested two MVA SARS-CoV-2 vaccines in mice. One of them, MVA/S, used the complete spike protein of coronavirus to induce strong neutralizing antibodies and a strong killer CD8 T cell response against SARS-CoV-2.

“Generating neutralizing antibodies is an important component of a successful COVID-19 vaccine because the antibodies can block the virus from entering the body’s cells,” says Amara, who is Charles Howard Candler professor of microbiology and immunology at Emory University School of Medicine and a researcher in Yerkes’ Division of Microbiology and Immunology. “It’s as important to activate CD8 T cells that can clear infected cells, so this allows us to approach halting the virus two ways simultaneously. The CD8 T cells also provide ongoing value because they are key to working against other variants of the virus, especially if antibodies fail.”

Based on the encouraging study results in mice, Amara’s team advanced the MVA/S COVID-19 vaccine into a study with 10 rhesus monkeys at Yerkes. For five animals, the researchers gave two doses of the vaccine a month apart and then challenged them with SARS-CoV-2. The researchers also challenged a group of five monkeys that received a placebo MVA vaccine, which did not contain any genes from the COVID-19 virus. The virus grew to high levels in the lungs of all five placebo animals by the second day, but was below detection limits in all five MVA/S-vaccinated animals.

“Comparing the virus in vaccine and placebo groups provided clear results the MVA/S vaccine is safe and effective against SARS-CoV-2,” says Amara. “These results are even more promising because the MVA/S-vaccinated animals did not show any signs of inflammation in the lungs such as what medical professional are seeing in humans who have COVID-19.”

Rafi Ahmed, PhD, director of the Emory Vaccine Center, credits Amara for his comprehensive approach:

“Based on decades of research, we know MVA vaccines are safe, effective and can be used in combination with other vaccines, including mRNA vaccines, to enhance the immune system’s response. The Emory MVA COVID-19 vaccine, which builds on the MVA HIV vaccine Dr. Amara co-developed that recently completed phase 2a human clinical trials, scores multiple goals by producing neutralizing antibodies, inducing killer CD8 T cells and preventing lung inflammation. This multi-layered approach to developing a COVID-19 vaccine is well positioned to fight the current strain of SARS-CoV-2 as well as the variants we’re beginning to see.”

“My research team and I as well as the entire Yerkes community are excited to move the Emory MVA COVID-19 vaccine forward,” says Amara. “The world needs multiple COVID-19 vaccines to meet the demand. Our vaccine can stand alone as well as complement the available mRNA versions. It’s a perfect combination of scientific expertise and collaboration, and commitment to improving human health.”

Amar’s team will continue their work on COVID-19 vaccines, with one study focusing on the effectiveness of a single dose of the Emory MVA COVID-19 vaccine. A convenient single dose regimen could prove especially valuable to ensure a high rate of vaccine uptake. Amara received two FastGrant awards to supplement his NIAID grant and expedite this follow-up COVID-19 research.

In a second study, Amara’s team is focusing on inducing broader T cell responses capable of fighting new COVID-19 variants and other human coronaviruses.

“The newly designed vaccines aim to induce T cells against multiple other genes of the virus in addition to targeting the spike protein,” says Amara. “This requires inserting multiple genes of the coronavirus into the vaccine, which can be challenging. MVA, however, is well-suited for this because of its unique capacity to carry extra genes.”

Amara’s research team includes Nandakishore Routhu, PhD (postdoc), Sailaja Gangadhara, PhD (research associate), Narayanaiah Cheedarla, PhD (postdoc), and Venkata Satish Bollimpelli, PhD (postdoc), all four co-lead authors, as well as Ayalensh Shiferaw (research specialist). Amara and his team worked in close collaboration with the laboratories of Mehul Suthar, PhD, and Steve Bosinger, PhD. Suthar is an assistant professor in the Emory SOM Department of Pediatrics and an EVC researcher. Bosinger is an assistant professor in the SOM Department of Pathology & Laboratory Medicine, an EVC researcher as well as a researcher in Yerkes’ Division of Microbiology and Immunology, and director, Yerkes Nonhuman Primate (NHP) Genomics Core.

In addition to the NIAID grant 3R01AI148378-01S1, the MVA vaccine study reported in this release is supported in part by the Yerkes National Primate Research Center base grant P51OD011132 from the NIH Office of the Director, Office of Research Infrastructure Programs.

Grant amounts (direct + indirect):

3R01AI148378-01S1 $582,625/for 2 years

P51OD011132 $10,540,602/yr

Fast grant 1, $250,000

Fast grant 2, $350,000

Note: The amounts listed above are for the full grants. Only a portion of the P51 will support infrastructure needs of the COVID-19 vaccine study reported in this news release.

Rama Amara, PhD

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