amfAR, The Foundation for AIDS Research

Countdown

Investment Grants: Bringing Bioengineers to Cure HIV

Request for Proposals

Program Overview

amfAR’s $100 million Countdown to a Cure initiative is aimed at developing the scientific basis of a cure for HIV by the end of 2020. The urgency of our goal demands that we direct our funding to studies that uncover vital knowledge directly applicable to curing HIV in people living with HIV/AIDS. amfAR expects that this RFP will solicit revolutionary ideas and unconventional approaches that inform, design and evaluate curative interventions.

Persistent reservoirs of virus not cleared by antiretroviral therapy (ART) represent the main barrier to a cure for HIV and, as evidenced by the “Berlin patient,” removing the reservoir is one mechanism by which a cure can be accomplished. amfAR intends to fund research that explores all curative approaches, including reservoir removal, as well as other mechanisms that would result in ART-free remission without the risk of transmission for at least five years.  We encourage the submission of proposals that explore novel, high-risk, and potentially high-impact ideas.

amfAR’s Investment Grants aim to harness technology developed by bioengineers to solve the problems posed by the viral reservoir. Recent advances in nanomachines, synthetic biomarkers, in vivo sensors, multi-omic single cell platforms and other technologies have yet to be evaluated for their usefulness in curing HIV. Investment Grants provide a funding mechanism through which potentially groundbreaking, early stage approaches are encouraged, regardless of risk or scalability, by requiring collaborations between bioengineers and HIV cure scientists.

Funding Opportunity Description: Investment Grants

Investment Grants are milestone-driven grants that provide funding of up to $1.5 million over four years in three phases. See table below for funds allotted to each phase. Applicants must be HIV scientists focusing on cure research and are required to collaborate with bioengineers employing technologies that have the potential to address the specific areas of interest. Bioengineers interested in applying are required to collaborate with HIV cure scientists.

 

Phase

Award amount

I

$200,000

II

$500,000

III

$800,000

 

Investment Grants are expected to be completed in four years and the length of each phase should be dictated by the PI, however, reasonable time allocations should be made to ensure completion of all phases within the prescribed time.  

Specific Areas of Interest

The main barrier to a cure for HIV is the presence of a viral reservoir that persists despite suppressive ART. The majority of the viral reservoir is in CD4+ T cells in the form of provirus—HIV DNA that is integrated into the host genome. To date, there is no single or combined signature of biomarkers that can distinguish the viral reservoir from uninfected cells during suppressive ART. Eliminating or permanently disabling the viral reservoir will result in a cure for HIV. Thus, specific areas of interest are:

  • biomarkers or molecular signatures that can distinguish the reservoir from uninfected cells in vivo during suppressive ART

  • mechanisms to induce cell death specifically in HIV-infected cells in vivo

  • mechanisms to permanently disable the provirus in vivo

The goal of each area of interest is to develop tools that will, at the end of four years, be ready for Phase I clinical trials.  Each proposal must address the specific area of interest in vivo in an appropriate animal model. Research plans that do not include an in vivo component will not be reviewed.

Research Plan

The proposed research plan must be responsive to at least one specific area of interest and delineate all phases of the work for all milestones within that area. Research plans falling outside of the prescribed areas of interest will not be considered. Applicants should ensure that the research plan is written for reviewers who are well-versed in the HIV cure field.  

amfAR will not consider iterations of previously tested ideas that resulted in only modest advances or studies that would result in incremental knowledge. Collaborations must be meaningful and capitalize on the verifiable expertise of both parties. This RFP does not fund prevention studies or non-biomedical research-based activities.  

Applicants may submit inquiries to amfAR (grants@amfar.org) regarding the development of research plans to ensure that such plans fit within the intended scope of this RFP. No phone calls will be accepted. Responses to all inquiries received will be posted here as Frequently Asked Questions (FAQs). The FAQ will be updated periodically, so please check for the current version before e-mailing an inquiry.

Proposal requirements:

  • collaborative work plan involving the HIV cure scientist and the bioengineer

  • a device, technology or tool that has not been tested in HIV

  • in vivo studies in an appropriate animal model

  • the use of clinical HIV viral isolates or SIV model viruses if using non-human primates

  • the use of clinically relevant tissues and primary cells

Milestones and Tasks

Investment Grant funds will be distributed in three phases. Advancement to the next phase is dependent on 1) the achievement of a predetermined and mutually agreed upon milestone and 2) on amfAR’s research priorities. Provisions can be made and negotiated during the performance period as needed to ensure maximum agility, allow for creativity, and keep pace with innovations in the field. Milestones should be proposed by the investigator at the LOI stage and will be negotiated at the time of notice of award.

amfAR expects that the research plan will be completed in four years and that each phase is allotted a reasonable amount of time to be completed. In order for amfAR to evaluate whether the proposed work is on course for completion during the phase and in line with stated objectives, project metrics will be evaluated through progress reports.

Generally, we expect technology development to be accomplished in Phase I. Phase II should translate that technology in vitro to primary cells and/or tissues.  Phase III should test the technology in vivo in an appropriate animal model. However, amfAR understands these milestones can differ significantly depending on the stage at which each technology is beginning. Thus, reasonable milestones outside of that described above will be reviewed.  

Example of Proposed Milestones and Tasks

A team proposes that a nanomachine, Death Star, which currently detects influenza in vitro and activates apoptosis via caspase X, can be modified to cure HIV. The team is addressing specific area #2- mechanisms to induce cell death specifically in HIV-infected cells in vivo. This team will write milestones that redesign the technology in Phase I, test the technology in primary cells in Phase II and test it in non-human primates in Phase III.

Their milestones and tasks could be written as follows:

  • Milestone I- Demonstrate that Death Star specifically detects HIV/SIV viral isolates and activates caspase X only when HIV is detected.

  • Task 1- Redesign Death Star to detect clinical HIV viral isolates and two SIV model viruses. Criteria for success: Activation of caspase to at least 80% of positive control will be detected in 90% of HIV clinical viral isolates and two SIV model viruses.

    • Task 2- Test redesigned Death Star for specificity to HIV/SIV vs. other clinically relevant viruses for caspase X activation. Criteria for success: 0% caspase activation is observed in samples testing Human Endogenous Retrovirus, Herpes Simplex Virus, Human papilloma virus, Rhinovirus and Influenza virus.

  • Milestone II- Demonstrate that Death Star signals death specifically in HIV/SIV infected cells in vitro.

    • Task 1- Determine best formulations to deliver Death Star into T cell lines measuring toxicity to non-infected cells. Criteria for success: Death Star toxicity to non-infected cells is 0% and equal to that of vehicle only control.

    • Task 2- Test Death Star in primary HIV/SIV infected and non-infected cells for toxicity and stability. Criteria for success: At dose Z, Death Star is 99% toxic in HIV/SIV infected cells and 1% toxic in non-HIV/SIV infected primary cells. Death Star is stable for at least 4 weeks in primary cells.

  • Milestone III- Demonstrate that Death Star delays viral rebound after cART cessation

    • Task 1- Determine dose response in vivo in non-human primates for toxicity to Death Star in uninfected animals. Criteria for Success: At dose Y, Death Star displays zero adverse events in all non-infected animals.

    • Task 2- To evaluate Death Star for its ability to delay viral rebound after cART cessation. Criteria for success: Death Star delays viral rebound for at least 1 year compared to non-treated animals.

Application Review and Selection Process

Selection of applications is a four-step process, as follows:

Letters of Intent (LOIs) are reviewed by amfAR staff to ensure that eligibility requirements are met and that the research proposed is in line with amfAR objectives and is responsive to the RFP. LOIs that meet the criteria proceed to a peer review process.

LOIs are reviewed by leading HIV experts and scored based on the following criteria:

  • expected impact on HIV cure
  • innovation and novelty of the proposed work
  • plan to overcome obstacles described with the technology/tool/platform proposed
  • competency and track history of members of the team
  • feasibility of work plan

Applicants with the highest-scoring LOIs are invited to submit full applications. Full applications are reviewed by members of amfAR’s Scientific Advisory Committee and a select group of bioengineers. Each application will be discussed during an in-person meeting to assess the merit of each application with respect to:

  • expected impact on HIV cure
  • ability of the team to overcome obstacles in reaching milestones
  • innovation and novelty of the proposed work
  • possible scientific or budgetary overlap

Successful applications are chosen based on reviewer comments and on amfAR priorities.

Award Information

Eligibility

Institutions

Applications are accepted from nonprofit research institutions worldwide; applications are not accepted from individuals or for-profit entities. However, although the Principal Investigator must be from the applicant institution, research teams may include members from, and budgets may include subcontracts or subawards to, for-profit entities.

Principal investigators:

  • Must hold a doctoral level degree; it is not required that the principal investigators hold a faculty-level position.

  • Collaborating PIs need not be from the same institution.

  • The HIV cure PI will be expected to lead one of the component projects, coordinate the development, implementation and analysis of the project as a whole, and be responsible for overall financial management and the preparation and submission of required reports.

Collaborating bioengineer:

  • Must hold a doctoral level degree; it is not required that collaborator hold a faculty-level position.

Funding Restrictions

  • There is no direct cost maximum; however, indirect costs may not be greater than 20% of direct costs, less subawards. The total cost maximum is $1,500,000.

  • This RFP solicits projects to be completed in the four-year period starting February 1, 2017.

Requesting LOI Application Forms and Credentials

Submission of Letters of Intent is a two-step, online process.

  • You must request log-in credentials no later than 3:00 p.m. EDT on Friday, September 23. Be aware that it generally takes one business day to process credential requests. If credentials are requested on Friday, September 23, they may not be sent until Monday, September 26.

  • CLICK HERE to request log-in credentials. Username, password and a link to the submission portal will be sent to the email address provided.

  • Use the log-in information to complete and submit the LOI online through the portal. LOIs must be submitted via the portal no later than 3:00 p.m. EDT on Tuesday, September 27.

Please be sure to request credentials and forms with adequate time to prepare a Letter of Intent. Deadline extensions will not be provided.

Important Dates

Letters of Intent due: September 27, 2016

Invite full applications: November 8, 2016 (tentative)

Full applications due: December 15, 2016 (tentative)

Performance period begins: February 1, 2017 (tentative)