Scanning electron micrograph of an H9 T cell with HIV, colorized orange and green.
Credit:NIAID
by Jeanne Marrazzo, M.D., M.P.H., NIAID Director
The HIV research community is led by scientists with deep personal commitments to improving the lives of people with and affected by HIV. Some researchers, like me, have pursued this cause since the start of the HIV pandemic, growing our careers studying HIV from basic to implementation science. Our collective decades of work have generated HIV testing, prevention and treatment options beyond what we could have imagined in the 1980s. Those advances enable NIAID to explore new frontiers: expanding HIV prevention and treatment modalities, increasing understanding of the interplay between HIV and other infectious and non-communicable diseases, optimizing choice and convenience, and building on the ever-growing knowledge base that we need to develop a preventive vaccine and cure. The next generation of leaders will bring these concepts to fruition, and we need to welcome and support them into the complex and competitive field of HIV science.
Click below for a video in which NIAID grantees and I discuss the value and experience of early-stage HIV investigators (the audio described version is here):
NIAID wants to fund more new HIV scientists and we have special programs and funding approaches to meet that goal. This week, the NIH Office of AIDS Research will host a virtual workshop on early-career HIV investigators tomorrow, April 24, and NIAID will host its next grant writing Webinars in May, June, and July.
For more information about programs and support for new and early-stage investigators as well as people starting to implement their first independent grant, visit these NIAID and NIH resources:
The goal of the NOSI is to encourage research to understand causes and mechanisms of IEIs, enable early detection and molecular diagnosis, and support the development of strategies to treat and eventually cure these disorders.
Advances in whole genome sequencing and similar state of the art, high throughput methods have led to accelerated discovery of new genes and molecular pathways responsible for aberrant or sub-optimal immune responses, which, in turn, can lead to increased infections or other diseases related to the immune system. Identification of molecules and pathways associated with IEIs should inform development of novel diagnostic methods and enable rational design of personalized therapies based on patient-specific diagnoses.
Review the NOSI for additional research areas of specific interest. Interested applicants may contact NIAID through the email address listed at the end of this article to determine responsiveness of applications on research topics not listed.
Application and Submission Information
This notice applies to NIH Standard Due Dates on or after June 5, 2024, and subsequent receipt dates through March 16, 2027.
Submit applications for this initiative using one of the following notices of funding opportunities (NOFOs) or any subsequent reissues through the expiration date of this notice.
Budgets, project periods, and receipt dates for applications submitted under this NOSI follow standard requirements for R01, R21, and R03 NOFOs listed above. Therefore, refer to your chosen NOFO for those application requirements.
All instructions in the SF 424 (R&R) Application Guide and the NOFO used for submission must be followed, with the following addition:
Applicants must include “NOT-AI-24-024” in the Agency Routing Identifier field (box 4B) of the SF 424 R&R form. Applications without this information in box 4B may not be directed to the correct program officer.
Contact Information
If you have any questions about the NOSI, reach out to Dr. Maggie A. Morris Fears at maggie.morrisfears@nih.gov or 301-761-5444.
Contact Us
Email us at deaweb@niaid.nih.gov for help navigating NIAID’s grant and contract policies and procedures.
Electron micrograph imagery of bacteria that cause three sexually transmitted infections: chlamydia (left), gonorrhea (center), and syphilis (right). Bacteria are colorized orange/gold.
Credit:NIAID
Sexually transmitted infections (STIs) are caused by bacteria, viruses, or parasites. STIs have a devastating impact on adults and infants and annually affect millions of people in the United States. Certain STIs can increase a person’s risk of developing cancer and increase the likelihood of acquiring or transmitting HIV. In addition, STIs can cause long-term health complications, especially in the reproductive and central nervous systems. In rare cases, they can lead to serious illness or death.
NIAID supports research across the spectrum from basic to clinical science to develop effective diagnostic, preventive and therapeutic approaches to STIs in alignment with the National STI Strategic Plan. In recognition of National STI Awareness Week, NIAID shares a snapshot of new projects and recent scientific advances in STI research.
Improving treatment for syphilis and trichomoniasis
New reports of syphilis and congenital syphilis are increasing at an alarming rate in the United States. Syphilis is caused by the bacterium Treponema pallidum. Benzathine penicillin G (BPG) is one of only a few antibiotics known to effectively treat syphilis. There is currently a shortage of BPG, and some people are allergic to penicillin antibiotics. In February 2024, NIAID convened a workshop with a wide range of experts on alternative therapies to BPG for the treatment of adult syphilis, neurosyphilis, and syphilis in pregnant persons and infants. The workshop addressed preclinical evaluation of candidate drugs, the potential need for studies on how candidate drugs are processed in the body during pregnancy, and how to approach clinical trials of treatment for congenital syphilis. This work is part of NIAID’s comprehensive portfolio of syphilis diagnosis, prevention, and treatment research.
Trichomoniasis is the most common parasitic STI, caused by Trichomonas vaginalis. Trichomoniasis can increase the risk of getting or spreading other STIs, including HIV. The parasite can also cause inflammation of the cervix and the urethra. T. vaginalis is treated with an antibiotic drug class called nitroimidazoles. The currently recommended nitroimidazole, called metronidazole, cures 84-98% of T. vaginalis cases but does have high rates of breakthrough infection. A new project led by Tulane University will examine a single dose of secnidazole, a medicine in the same drug class, as a more effective and cost-effective treatment option for women and men.
Developing a vaccine for herpes simplex virus 2
Herpes simplex virus 2 (HSV-2) is a common subtype of herpes simplex virus that is transmitted through sexual contact. The Centers for Disease Control and Prevention estimates that 18.6 million people aged 15 years and older United States live with HSV-2. In severe cases, HSV-2 may lead to life-threatening or long-term complications. There is no licensed preventive HSV-2 vaccine, and there is no cure. A new project led by the University of Pennsylvania seeks to define correlates of protection for HSV-2, meaning they intend to identify immune processes involved in preventing HSV-2 disease. They will do this by analyzing laboratory samples from animal studies of a promising preventive vaccine candidate that they developed with prior funding. That vaccine candidate is also now in an industry-sponsored early-stage clinical trial. The same project will expand on the HSV-2 targets in the preventive vaccine to develop a therapeutic vaccine concept to reduce recurrent outbreaks. This research responds to the scientific priorities in the NIH Strategic Plan for Herpes Simplex Virus Research.
Increasing fundamental knowledge of bacterial vaginosis
Bacterial vaginosis (BV) results from an imbalance in the vaginal microbiome. BV can be caused by sexual activity, douches and menstrual products. BV can increase women’s biological susceptibility to HIV and other STIs and can cause premature birth or low birthweight if untreated in pregnant people. In a recent publication, NIAID-supported researchers, led by researchers at the University of Washington and University of California San Diego, shared findings on how damage to the vaginal skin barrier occurs during bacterial vaginosis. Those skin barrier cells, called epithelial cells, are covered in carbohydrate molecules called glycans. The research team found that people with BV had damaged glycans on their vaginal epithelial cells. They suggested that future work should examine the relationship between treatment and restoration of normal glycans. If an association is detected, it could help healthcare providers monitor for successful treatment outcomes to reduce the likelihood that BV will return after a course of treatment. The findings were published in Science Translational Medicine.
These activities are among the research investments in NIAID’s STI portfolio. For more information on STIs, please visit:
Colorized transmission electron micrograph of HIV-1 virus particles (blue) budding and replicating from an H9 T cell (bright green). The virus particles are in various stages of maturity, which accounts for differences in shape. Captured at the NIAID Integrated Research Facility in Fort Detrick, Maryland.
Credit:NIAID
The National Institutes of Health recently issued $26M in awards to HIV research institutions in its fifth year supporting implementation science under the Ending the HIV Epidemic in the U.S. (EHE) initiative. These awards are the latest investments in a program that is rapidly and rigorously generating evidence to inform the unified domestic HIV response by agencies in the Department of Health and Human Services.
The EHE initiative aims to achieve a 90% reduction in the number of new HIV infections in the United States by 2030. Since the initiative was announced in 2019, NIH has contributed by supporting implementation science projects through its network of Centers for AIDS Research (CFAR) and the National Institute of Mental Health (NIMH) AIDS Research Centers (ARC). CFARs are co-funded by 11 NIH institutes and centers (ICs), including the National Institute of Allergy and Infectious Diseases (NIAID). NIH ICs provide scientific stewardship to participating institutions in collaboration with the Fogarty International Center and the NIH Office of AIDS Research, which coordinates the NIH HIV research program across the agency. CFAR and ARC-affiliated investigators conduct research in jurisdictions that are disproportionately affected by HIV, and many of the CFAR and ARC member institutions are based in these communities.
VIDEO: Jeanne Marrazzo, M.D., M.P.H., NIAID Director, discusses NIH’s role in the EHE (audio description version here):
NIH EHE projects enable academic institutions to partner with state and local leaders to jointly translate implementation research findings into improved delivery of HIV testing, prevention, treatment, and response services for priority populations and in priority geographic areas. Projects funded this year are designed to increase and share available knowledge on locally appropriate strategies to:
detect and respond to HIV “clusters,” i.e., groups of people and communities experiencing rapid HIV transmission;
leverage pharmacies as HIV service locations;
ensure uninterrupted HIV care for people returning to their communities following incarceration; and
develop approaches that address intersecting diseases and conditions that exacerbate health inequities and impact HIV outcomes, including such as viral hepatitis, sexually transmitted infections, and substance use and mental health disorders.
Since Fiscal Year 2019, NIH has funded 253 projects across 50 geographic areas prioritized by EHE. The latest EHE awards to CFARs and ARCs support 47 projects, 8 implementation science hubs, and 1 coordinating center. Hubs provide technical support, coaching, training, and consultative services to funded EHE research teams. The coordinating center provides infrastructure for collaboration and sharing best practices in HIV implementation science. In addition to the CFAR/ARC supplements, NIH supported multiple larger research projects in 2023, including 3 R01 awards, 2 R34 awards, and 1 coordinating center. In September 2023, NIH released a Notice of Special Interest to solicit project proposals from independent investigators for Fiscal Year 2024.
EHE Project Spotlights
The knowledge generated by NIH EHE projects is reviewed with HHS EHE partners to accelerate learning and program improvement. Two projects below illustrate how EHE implementation science projects have already enhanced locally tailored HIV service delivery:
Miami, Florida
Miami-Dade County, Florida has one of the highest rates of HIV incidence in the United States, and yet use of pre-exposure prophylaxis (PrEP) to prevent HIV acquisition remains relatively low. Researchers at the University of Miami, in collaboration with the Florida Department of Health (DOH) and a local community-based organization called Prevention305, developed a process to apply real-time DOH epidemiologic data to prioritize new geographic locations for placement of their mobile PrEP clinics. In collaboration with community partners, the project developed a new outreach approach: “Test-to-PrEP,” in which people using PrEP are engaged to distribute free HIV self-tests and PrEP referrals through their social networks. They have worked with 100 current PrEP clients to engage members of their social network with information about PrEP provide them with HIV self-tests. More than one third of the 117 HIV self-test kit recipients who confirmed they used the test reported they had not previously known about PrEP. Self-reported knowledge and likelihood to use PrEP increased significantly after kit receipt. PrEP clients also reported feeling comfortable with the distribution and enthusiastic about the strategy. Their work has provided a blueprint for mobile HIV prevention and related services as a strategy to interrupt further transmission.
Mobile clinic service team in the Liberty City neighborhood of Miami, Florida
Credit:University of Miami
Shelby County, Tennessee
Rural areas like Shelby County pose distinct challenges to HIV service delivery, including a lack of outpatient providers and fragmented health care and social services, as well as stigma and medical mistrust. To overcome these barriers, researchers from University of Massachusetts, Lowell, in collaboration with the University of Memphis and the Shelby County Health Department, used an implementation research approach to adapt and provide an evidence-based training and capacity-building program in HIV care for existing community health workers (CHWs), with input from HIV care providers, people with HIV, and CHWs. CHWs are frontline public health workers who are also members of the community they serve. The team has trained 67 CHW to support HIV care across eight agencies and has provided coaching sessions to supervisors around how to sustain this workforce. They are assessing the sustainability and effectiveness of this program in addressing service gaps and improving health outcomes through follow-up surveys with health care agency staff and county health leaders.
Community health worker Michelle Anderson discussing culturally relevant care HIV care with colleagues in Memphis, Tennessee.
Credit:University of Massachusetts, Lowell
In addition to NIH, HHS agencies and offices participating in EHE include the Centers for Disease Control and Prevention; the Health Resources and Services Administration; the Indian Health Service; the Office of the Assistant Secretary for Health; and the Substance Abuse and Mental Health Services Administration.
To view a complete list of NIH research projects supported with EHE initiative funding, please visit the awards page.
Butts, SA et al. Addressing disparities in Pre-exposure Prophylaxis (PrEP) access: implementing a community-centered mobile PrEP program in South Florida. BMC Health Services Research. DOI 10.1186/s12913-023-10277-1 (2023).
Johnson, AL et al. “Test-To-PrEP”: Assessing Reach and Adoption of a New Approach to Increase HIV Testing and PrEP Knowledge Using HIV Self-Test Kit Distribution Through PrEP Clients' Social Networks. Journal of Acquired Immune Deficiency Syndromes. DOI 10.1097/QAI.0000000000003294 (2023).
Rajabiun, S et al. Using Implementation Science to Promote Integration and Sustainability of Community Health Workers in the HIV Workforce. Journal of Acquired Immune Deficiency Syndromes. DOI 10.1097/QAI.0000000000002966 (2023).
Colorized scanning electron micrograph of a healthy T lymphocyte (green), also known as a T cell.
Credit:NIAID
Stem Cell Changes Rejuvenate Immune System in Aged Mice
NIAID, Stanford Exploring Potential for Revitalizing Human Immunity
Aging is associated with a reduced ability to generate immune responses against novel infections, as was recently illustrated by the high mortality among older people during the COVID-19 pandemic. Using a mouse model of human aging and disease, NIAID scientists and Stanford University colleagues have shown that immune systems of aged laboratory mice can be made more youthful and effective at fighting disease by depleting a subset of haematopoietic stem cells (HSCs). The researchers think the method they developed may have potential for rejuvenating immunity in elderly people and are pursuing further study. Their findings are published in Nature.
When the immune system is young, balanced HSCs (bal-HSCs) dominate, producing a healthy mix of lymphoid and myeloid cells. Lymphoid cells develop into B and T cells that can adapt to new infections. Myeloid cells develop into non-adaptive and inflammatory cells that drive the immediate response of the innate immune system.
As the immune system ages, myeloid-biased HSCs (my-HSCs) start to dominate, increasing inflammatory responses and decreasing the number of lymphoid cells that can adapt to novel infections. The scientists hypothesized that if they could increase the proportion of bal-HSCs in an aged immune system by reducing the number of my-HSCs, the adaptive immune response could be returned to a more youthful state.
To test their hypothesis they identified my-HSC-specific genes in laboratory mice and then developed three methods using antibodies to deplete the targeted my-HSC gene products. Within a week the team began observing a “rebalancing” of the immune system, with increases in lymphoid cells and decreases in myeloid cells. Markers of inflammation and “immune exhaustion” associated with age also were decreased. Even after 16 weeks, a single treatment remained effective in the aged mice.
To test for functionality of the immune response, they challenged aged animals with mouse retroviruses. They observed increased virus-specific T-cell development in treated mice compared to aged untreated controls, reduced pathology, and significantly increased virus control, with four of nine treated mice completely clearing the infection.
“Taken together, these results demonstrated that my-HSC depletion in aged mice significantly improved immune responses to live viral infections,” the researchers write.
The scientists found that the my-HSC-specific antigens targeted for depletion in mice are also present in human my-HSC, suggesting that similar protocols could be used in humans.
“These experiments represent the first steps towards identifying therapeutic targets to deplete human my-HSCs and to rejuvenate the aged immune system using this strategy,” according to the researchers.
It is well known that the microbiome plays a role in almost every aspect of human physiology, yet much remains to be understood about the specific mechanisms of how commensal microbes affect human cellular function. The Host Microbe Symbiosis unit focuses on such mechanisms, with a particular focus on innate immune signaling and homeostasis at barrier sites such as the skin. Although the immune system likely expends most of its energy interacting with the multitude of organisms that occupy the human body, our knowledge of these interactions and how they influence the function of the immune system remains fairly limited.
As allergic and autoimmune diseases and antibiotic-resistant infections become more common, it becomes increasingly necessary for us to better understand how commensal microbes shape immunity and homeostasis. The overarching principle of our research is that commensal organisms influence innate immune signaling at barrier sites via interactions with epithelial and immune cells and direct competition with pathogens. Therefore, understanding both the signaling between commensals and human cells and microbial interspecies interactions can lead to the development of targeted microbial therapeutics that reduce susceptibility to infection and maintain optimal function of barrier sites in the body.
One such targeted microbial therapeutic is Roseomonas mucosa. This commensal skin bacteria was developed as a topical probiotic for atopic dermatitis by Dr. Ian Myles, also of the Laboratory of Clinical Immunology and Microbiology. R. mucosa serves as a model for how microbes can be used to effectively treat dysbiotic disease and restore optimal function to the skin, and it is the focus of our research thus far in the Host Microbe Symbiosis Unit. Our research is defining the mechanisms by which R. mucosa mediates immune regulation and supports homeostasis of the skin, particularly through its interaction with TLR5 and its bacteriostatic effects on Staphylococcus aureus. These studies provide a framework for future studies of other host-commensal interactions.
The main techniques utilized in our study of host-commensal interactions are in vitro modeling with primary human cells, mouse models, quantitative proteomics, and various immunoassays to evaluate the interaction in three areas: initial contact of the microbe with host tissue (adhesion), downstream signaling from the activated receptor (e.g., TLR5), and the outcomes of the activated signaling pathway (cytokine, chemokine, antimicrobial peptide production, cell proliferation). A particular focus of the lab is that the downstream effects of interaction between commensal bacteria and TLRs appear to differ from the activation of TLRs by pathogen-derived ligands in a way that likely fine-tunes inflammatory responses for the host.
