Notice

Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted.

Updates regarding government operating status and resumption of normal operations can be found at USA.gov.

Selected NIAID Research Advances of 2015

 

Message from the Director

The National Institute of Allergy and Infectious Diseases (NIAID) conducts and supports research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases.

This slideshow highlights notable scientific advances made by NIAID researchers and NIAID-funded scientists at domestic and international institutions during fiscal year 2015. Some advances brought us closer to vaccines and treatments for HIV, influenza, and Ebola. Others offered new insights into food allergy prevention, autoimmune diseases, and drug-resistant infections. All are representative of how public investment in biomedical research drives scientific progress and benefits human health.

For more than 60 years, NIAID research has advanced the understanding, diagnosis, prevention, and treatment of many of the world’s most intractable and widespread diseases. Through our sustained commitment to basic and clinical research, we will continue to address the health challenges facing people in the United States and around the world for years to come.

Anthony S. Fauci, M.D.
Director
National Institute of Allergy and Infectious Diseases
National Institutes of Health

 

Preventing the Development of Peanut Allergy

Food allergies are a growing public health concern in the United States and around the world, but currently no approved therapies are available for food allergy prevention or treatment.

In February, NIAID-funded researchers reported results from a clinical study called Learning Early About Peanut Allergy (LEAP). The LEAP study was based on the observation that Israeli children, who typically consume peanut-containing foods beginning early in infancy, have much lower rates of peanut allergy than Jewish children of similar ancestry residing in the United Kingdom. The study tested the hypothesis that the lower rate of peanut allergy among Israeli children resulted from consuming, rather than avoiding, peanut-containing foods in the first years of life, and that a similar strategy would work in a different location.

The team found that among infants in the United Kingdom who were at high risk of developing peanut allergy, regular and frequent eating of peanut-containing foods beginning in infancy was safe and led to an 81 percent reduction in subsequent development of peanut allergy by age five, compared to infants who avoided peanut-containing foods. A benefit of this magnitude in preventing food allergy is without precedent and indicates that this new prevention strategy will change clinical practice.


Caption: Bowl of peanuts.
Credit: Pixabay

 

Underscoring the Importance of Early HIV Treatment

Current U.S. HIV treatment guidelines recommend that all asymptomatic HIV-infected people take antiretroviral drugs, regardless of their CD4+ cell count, a measure of immune system health. Results from the NIAID-supported Strategic Timing of AntiRetroviral Treatment (START) study, which enrolled more than 4,600 HIV-infected people in 35 countries, offered clear-cut scientific evidence to support this recommendation.

The START findings showed that starting antiretroviral therapy early, without waiting for CD4+ cell counts to decline, prevented serious AIDS-related events, serious non-AIDS-related events, and death. The researchers tracked multiple non-AIDS-related events, including cardiovascular disease, end-stage kidney disease, liver disease, non-AIDS-related cancers, and deaths not attributable to AIDS. Overall, the risk of developing serious AIDS events, developing serious non-AIDS events, or death was reduced by 57 percent among those who received early treatment, compared to those who started treatment after their CD4+ cell counts had declined below a certain threshold. This reduction was not linked to age, sex, baseline CD4+ cell counts, geographic region, or country income level. In the early-treatment group, serious AIDS events were reduced by 72 percent and serious non-AIDS events were reduced by 39 percent.

The START findings conclusively demonstrate the benefits of early antiretroviral therapy for the health of individuals with HIV, aligning these benefits with the public health benefit of early treatment to prevent HIV transmission. These results firmly underscore the importance of offering immediate antiretroviral therapy to all HIV-infected patients.


An HIV-infected immune cell.
Credit: NIAID

 

Advancing Toward a Universal Flu Vaccine

Seasonal flu vaccines work by generating antibodies that target the head region of the lollipop-shaped viral protein hemagglutinin (HA), preventing the virus from entering and infecting cells. The HA head region frequently undergoes genetic changes as flu viruses evolve, making the antibodies produced against one strain ineffective against another. As a result, flu vaccines must be updated annually to best target the viruses predicted to spread and cause illness in a given year.

Scientists are working to develop a universal flu vaccine—one that confers durable protection against most influenza viruses. One possible approach is to create a vaccine that elicits antibodies targeting the HA stem. Unlike the head, the stem varies little among different influenza viruses.

NIAID scientists have developed a nanoparticle vaccine with a stabilized HA stem from an H1N1 influenza virus. Investigators immunized mice and ferrets with the experimental vaccine and then exposed the animals to a lethal dose of H5N1 influenza. The vaccine elicited antibodies that completely protected mice and partially protected ferrets against disease.

Notably, the vaccine was created from an H1 HA stem but elicited protection against the different H5 HA subtype. Injecting antibodies from vaccinated mice into non-vaccinated mice protected the non-vaccinated mice against challenge with H5N1 influenza, confirming that the vaccine-induced antibodies served to protect the mice. Together, the results provide proof-of-concept that a vaccine that elicits antibodies that target the HA stem can offer broad protection against different influenza strains.


Influenza virus particles.
Credit: NIAID
 

Advancing HIV Prevention and Treatment

While antiretroviral therapies and pre-exposure prophylaxis have offered vital gains against HIV, daily adherence to the drug regimens can be a challenge, and better treatments are needed. Promising new preventive and therapeutic treatments are under development.

In one approach, NIAID-funded scientists created a new molecule called eCD4-Ig, which targets a conserved area of HIV that binds host cells prior to infection. By blocking this key area on the outer surface of HIV, the drug prevents the virus from infecting cells, and importantly, may be used to prevent or treat HIV infection.

The researchers tested eCD4-Ig in a monkey model of HIV infection with encouraging results. Using gene therapy, the researchers designed a way for host cells to make eCD4-Ig indefinitely. Monkeys that received the new therapy produced eCD4-Ig, which was detected in their blood, and were protected from infection during the 40-week study period.

Now the team is assessing the ability of eCD4-Ig to prevent infection against a wider range of HIV strains, in hopes of developing a therapy that can be used to prevent as well as treat HIV infections in people.


HIV budding from an immune cell.
Credit: CDC
 

Optimizing Antibiotic Treatment for Skin Infections

For decades, methicillin-resistant Staphylococcus aureus (MRSA) has been a leading cause of hospital-acquired infections. More recently, new strains of MRSA have emerged outside of healthcare settings. Known as community-associated MRSA, or CA-MRSA, these strains typically infect the skin and can cause complications including bacteria in the blood, the need for hospitalization or surgery, and in severe cases, death.

Two antibiotics that are no longer under patent, clindamycin and TMP-SMX, are recommended for treatment of CA-MRSA, but data comparing the effectiveness and safety of these drugs are lacking. To address this limitation, NIAID-supported researchers treated approximately 500 adults and children with uncomplicated skin infections with clindamycin or TMP-SMX for 10 days. They found that both treatments had high cure rates—89.5 percent for clindamycin and 88.2 percent for TMP-SMX. In addition, both drugs caused comparable, mild-to-moderate side effects, such as diarrhea and nausea.

The findings suggest that otherwise healthy people with uncomplicated skin infections acquired outside of hospitals can be treated inexpensively and successfully with either clindamycin or TMP-SMX.


MRSA being ingested by a human neutrophil.
Credit: NIAID
 

Advancing HIV Vaccine Design

HIV's unique ability to evade the immune system presents challenges for the development of an effective HIV vaccine. One way that HIV hides from the immune system is by continuously changing the shape of the so-called viral spike, a surface molecule where powerful antibodies potentially could bind to stop infection. This shape-shifting helps conceal key antibody-binding sites and exposes other sites on the virus that lure minimally effective antibodies.

In 2015, a research team led by NIAID scientists reported that they had engineered a protein to maintain the specific shape of the viral spike predicted to be most effective at stimulating the immune system to produce powerful anti-HIV antibodies. Previous work by the NIAID scientists and colleagues had suggested that basing a vaccine on a form of the viral spike called the closed, pre-fusion configuration may be most effective at teaching the immune system to neutralize HIV.

The shape of the viral spike typically changes shape in the presence of a common immune-cell receptor called CD4, but the new engineered protein remains in the closed, pre-fusion configuration, which is critical to elicit potent antibodies that broadly neutralize HIV. The researchers confirmed that the stabilized protein allows binding of effective antibodies but not ineffective ones.

The engineered viral spike provides the basis for development of new vaccine components that stimulate specific immune responses. However, more work remains to overcome other hurdles to eliciting broadly neutralizing antibodies against HIV.


Researchers working in the lab at NIAID’s Vaccine Research Center.
Credit: NIAID
 

Tracking Ebola Virus Evolution in West Africa

The 2014-2015 Ebola outbreak in West Africa was by far the largest outbreak since the virus was discovered in 1976. Researchers have studied the genetic sequences, or genomes, of Ebola virus to understand its origin, transmission, and other details useful for diagnosis, treatment, and development of vaccines.

In 2015, NIAID researchers compared virus samples taken from patients in Guinea, Sierra Leone, and Mali during different periods of time during the outbreak, and they found that Ebola virus in West Africa was undergoing relatively few mutations.

The study suggests that no genetic changes altered the virulence or transmissibility of Ebola virus, and that despite extensive human-to-human transmission during the outbreak, the virus was not mutating at a rate beyond what was expected. Furthermore, the genetic changes observed are not likely to impair diagnostic tests or change the efficacy of candidate vaccines or potential treatments.


Ebola virus (red) budding from the surface of an infected cell.
Credit: NIAID
 

Protecting Against a Variety of Influenza Strains

Scientists are working to develop a universal flu vaccine that protects against a variety of influenza A virus strains. Currently, due to constant variation in influenza viruses, seasonal flu vaccines are updated and tailored to the specific flu strains predicted to circulate and cause illness each year. The seasonal flu vaccines elicit antibodies that target the viral surface protein hemagglutinin (HA).

A vaccine cocktail developed by NIAID researchers has shown promise in inducing protective immunity in mice against a wide array of influenza viruses. The vaccine cocktail incorporates four of the 16 different HA subtypes: two typically found in human seasonal influenza viruses, H1 and H3, and two from avian influenza viruses that also can infect people, H5 and H7. The vaccine is made from non-infectious virus-like particles, or VLPs, that stimulate an immune response but cannot replicate or cause disease.

The NIAID scientists vaccinated mice with the VLP cocktail, then exposed them to lethal doses of several influenza viruses, including viruses with HA subtypes not included in the vaccine. Vaccinated mice were protected against influenza viruses with 1918 H1, 1957 H2, and avian H5, H6, H7, H10, and H11 HA subtypes. Overall, 94 percent of vaccinated mice survived viral challenge, as compared to 5 percent of mice not given the VLP vaccine. The investigators now are testing the VLP cocktail in ferrets. If the results are similar to those in mice, they plan to advance the vaccine to early-stage human clinical trials.


Influenza A virus.
Credit: CDC
 

Developing an Ebola Vaccine

The unprecedented scale of the 2014 Ebola outbreak in West Africa intensified efforts to develop a safe and effective vaccine. Scientists at NIAID’s Vaccine Research Center and Okairos, a biotechnology company acquired by GlaxoSmithKline, developed a candidate Ebola vaccine that contains segments of Ebola virus genetic material delivered by a carrier virus that causes a common cold in chimpanzees but no illness in humans. The NIAID/GSK vaccine provided rapid and durable protection against Ebola virus infection in monkeys and in 2014 was rapidly advanced to early-stage trials in humans.

Researchers at the NIH Clinical Center administered a low dose of the vaccine to 10 healthy volunteers and a higher dose to an additional 10 people. All 20 volunteers developed anti-Ebola antibodies within four weeks of receiving the vaccine, and antibody levels were higher in those who received the higher dose. In many volunteers, the vaccine also prompted production of immune cells called CD8+ T cells, which played a crucial role in protecting vaccinated animals from Ebola virus infection. In addition, the vaccine was well-tolerated, with no serious side effects observed in any of the volunteers.


A clinical trial volunteer receives an experimental Ebola vaccine at the NIH Clinical Center.
Credit: NIAID
 

Analyzing and Addressing Antibiotic Resistance

Antibiotics are powerful tools for fighting bacterial infection, but overuse and misuse of these drugs have led to the emergence of antibiotic-resistant bacteria. Results from two recent NIAID-supported studies provide insight into how antibiotic resistance develops and how the problem can be addressed.

NIAID-funded researchers analyzed isolates of Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), from KwaZulu-Natal, South Africa, the location of the largest global outbreak of extensively drug-resistant TB. By sequencing the genomes of hundreds of patient samples, they found that the precursor of the outbreak strain gained resistance to first-line antibiotics shortly after these drugs became available for clinical use, and that subsequent accumulation of additional resistance mutations occurred over decades.

Optimizing antibiotic dosing and treatment duration can be challenging, and antibiotic regimens are often based on trial-and-error or expert opinion. To address this, NIAID-supported investigators developed a theoretical model to help optimize dosing and aid rational design of antibiotic treatment strategies that could have an impact on antibiotic stewardship.

NIAID continues to pursue these and other strategies to understand and combat the growing problem of antibiotic resistance.


Mycobacterium tuberculosis.
Credit: CDC
 

Understanding the Genetic Causes of Immune Diseases

While many genetic risk factors have been linked to various diseases, how a genetic change causes susceptibility to a disease is not always clear. By studying healthy people, NIAID researchers and colleagues created an open-access, reference resource to aid the understanding of immune-mediated diseases.

The team analyzed blood samples collected from more than 600 twins and developed a screening method that could differentiate approximately 80,000 subsets of immune cells, or immune traits. By using twins, the researchers identified which immune traits were most likely heritable and thus regulated at the genetic level. They discovered 19 immune traits that were regulated by more than 240 genetic changes clustered within 11 areas of the human genome.

The results of this study have far-reaching implications, especially for researchers studying autoimmune disorders like multiple sclerosis, lupus, type 1 diabetes, and inflammatory bowel disease. For example, genetic changes in the FCGR2 gene are known risk factors for these autoimmune disorders. However, it remains unclear how FCGR2 influences such a range of disorders. The team identified previously unrecognized immune trait variations that depend on this gene and may contribute to disease. In this way, researchers can use the new database to see how a change in FCGR2 or another gene affects components of the immune system and, subsequently, incorporate this information into the design of future studies.


DNA strand.
Credit: National Human Genome Research Institute
 

Understanding Immune Cell Diversity

Immune T cells play a key role in protecting against infections by recognizing and responding to a variety of infectious microbes. The ability to recognize a large number of different pathogens stems from random rearrangement of genes for T-cell receptors (TCRs) that occurs during T cell maturation, resulting in the generation of as many as 100 million unique receptors per individual. This method of producing a diverse TCR repertoire also results in the occasional development of “self-specific” T cells capable of mounting an immune response against the body’s own tissues. Scientists had long thought that clonal deletion—death of self-recognizing T cells before they fully mature—efficiently removes almost all self-specific T cells from the repertoire.

New findings from NIAID-supported researchers show that although clonal deletion prunes the T cell repertoire, it does not completely eliminate self-specific T cells. The scientists found that self-specific cells were abundant in an inactive state in the blood of healthy adults. The researchers suggest that these weakly self-reactive T cells also recognize foreign pathogens, and their total elimination would create holes in the repertoire that pathogens could exploit to cause infection. By retaining a sizable pool of T cells with TCRs that weakly recognize self-antigens, the immune system improves its ability to recognize a wide range of pathogens. The findings provide new insights into immune system function and may aid future efforts to prevent autoimmune diseases.


T cells.
Credit: NIAID
 

Controlling HIV with Broadly Neutralizing Antibodies

Studying broadly neutralizing antibodies (bNAbs) that target multiple, diverse HIV strains promises to aid development of products to treat or prevent HIV infection. Scientists have shown that some bNAbs, including one called 3BNC117, can protect humanized mice and macaques against HIV and its monkey equivalent. However, little is known about their safety and effectiveness in humans.

In a study funded partially by NIAID, investigators found that a single infusion of 3BNC117 resulted in decreased HIV levels that persisted for as long as 28 days in HIV-infected people. The researchers conducted a small clinical trial involving 17 HIV-infected and 12 uninfected volunteers. Study participants received a single infusion of 1, 3, 10, or 30 milligrams of 3BNC117. The bNAb was generally safe and well-tolerated by all participants, with no serious side effects reported. Among HIV-infected volunteers, 3BNC117 had the greatest effect on the eight participants who received the highest dose, resulting in significant and rapid decreases in the amount of virus present in the blood.

These findings suggest that bNAbs can be safe and may have a substantial effect on controlling HIV levels in people. The results support further exploration of bNAbs for use in HIV prevention and treatment.


An HIV-infected T cell.
Credit: NIAID
 

Halting Progression of Multiple Sclerosis

Multiple sclerosis, a progressive autoimmune disease in which the immune system attacks the brain and spinal cord, affects more than 2.3 million people worldwide. Symptoms vary and can include disturbances in speech, vision, and movement. The most common form of MS, relapsing-remitting MS (RRMS), is characterized by periods of symptom flare-up or relapse followed by periods of recovery or remission. Over years, the disease can worsen and shift to a more progressive form.

Three-year results from an ongoing NIAID-supported clinical trial suggest that high-dose immunosuppressive therapy followed by transplantation of a person’s own blood-forming stem cells can induce sustained remission in some people with RRMS. Researchers tested this treatment regimen in 25 volunteers with RRMS who had relapsed and experienced worsened neurological disability while taking standard medications. After three years, nearly 80 percent of participants had survived without experiencing an increase in disability, a relapse of MS symptoms, or new brain lesions, even though they did not receive any MS drugs after transplant.

The researchers plan to follow participants for a total of five years. Final results from this and similar studies promise to help inform the design of larger trials to further evaluate this treatment strategy in people with MS.


Researchers analyzing patient samples in the laboratory.
Credit: NIAID
 

Demonstrating the Immune-Health Benefits of Early HIV Treatment

In many countries outside the United States, decisions on when to start treatment for HIV infection are based on the level of CD4+ T cells, a key measure of immune system health. Typically, CD4+ T-cell counts decrease in untreated HIV infection, and antiretroviral treatment may be initiated when levels have dropped below a certain threshold. New research funded by NIAID suggests that the best time to start treatment also should be based on how much time has elapsed since infection.

By analyzing data from the ongoing U.S. Military HIV Natural History Study, researchers found that starting treatment within a year of seroconversion—the period shortly after HIV infection when antibodies to the virus develop and become detectable—can improve immune health. They noted that an HIV-infected person’s CD4+ T-cell count is more likely to return to normal (defined as at least 900 cells per microliter of blood) if treatment starts within a year of seroconversion and at a CD4+ T-cell count of 500 or more. The scientists also found that starting treatment within a year of seroconversion and achieving a normal CD4+ T-cell count were associated with immune-health benefits, including reduced risk of developing AIDS.

These findings were further supported by results from a major NIAID-supported international clinical trial called START, which revealed that HIV-infected people have considerably lower risk of developing AIDS, AIDS-related diseases, and non-AIDS-related diseases if they start antiretroviral treatment sooner and at higher CD4+ T-cell counts.


Blood bags used to study HIV infection.
Credit: NIAID
 

Evaluating Flu Vaccine Design

Seasonal flu vaccines elicit antibodies that primarily target the viral surface protein hemagglutinin (HA), preventing the flu virus from entering and infecting cells. However, when flu viruses change, the vaccine-elicited antibodies may no longer match the new virus. Thus, seasonal flu vaccines are updated and tailored to the flu strains predicted to circulate each year.

In addition to HA, there is a second viral surface protein called neuraminidase (NA) that is not a main target of conventional flu vaccines. NA is expressed less frequently on the viral surface, and the majority of naturally occurring antibodies target HA. Nevertheless, NA plays key roles in influenza virus infection, and studies have shown that anti-NA antibodies correlate with reduced disease severity in people.

To explore the protective capacity of anti-NA antibodies, NIAID-funded researchers evaluated their effectiveness in a mouse model of flu infection. They found that anti-NA antibodies protected mice against flu infection. The antibodies also protected against lethal infection by dissimilar strains of flu virus with the same NA subtype, indicating that anti-NA antibodies can offer broad protection.

Next, the researchers examined samples from 12 people who received the 2004-2005 seasonal flu vaccine. They discovered that the vaccine did not efficiently induce anti-NA antibodies, and furthermore, NA content varies greatly among commercial flu vaccines. In the future, incorporating NA into flu vaccine design may offer better protection, particularly when the seasonal flu vaccine is mismatched and fails to target the circulating flu viruses.


3D print of influenza virus. The virus surface (yellow) is covered with hemagglutinin (blue) and neuraminidase (red).
Credit: NIH 3D Print Exchange
 

Understanding How Anti-HIV Antibodies Mature

Scientists are working to develop HIV vaccine regimens that stimulate the immune systems of uninfected people to produce broadly neutralizing antibodies (bNAbs) that target many HIV strains and develop naturally over time in a minority of HIV-infected people. These antibodies undergo an unusually complex development and maturation process and typically gain potency against HIV after the virus has established infection, presenting challenges for design of a preventive vaccine. Interaction of T follicular helper (TFH) cells with antibody-producing B cells is essential for antibody development and maturation. HIV affects this interaction in multiple ways, including by infecting and altering TFH cells.

Results from an NIAID study of monkeys infected with simian human immunodeficiency virus (SHIV), a virus containing components of HIV and the related monkey virus, offer insights into how anti-HIV antibodies mature and provide clues for vaccine development. The scientists investigated the relationships between the generation of bNAbs and aspects of TFH cells, B cells, and the virus during chronic SHIV infection. They found that the frequency and quality of TFH cells that specifically recognize the virus’ outer shell, or envelope, were linked to development of bNAbs.

Although more work is needed, the findings suggest that HIV vaccine regimens that incorporate stimulation of TFH cells and boost high-quality TFH cell populations may elicit production of protective bNAbs.


HIV virus infecting cell.
Credit: iStockphoto
 

Developing a Vaccine Against Epstein-Barr Virus Infection

Epstein-Barr virus (EBV) is one of the most common human viruses. It infects 9 out of 10 people at some point in their lives, although most experience mild or no symptoms. However, EBV infection also can cause more serious illness. EBV is the major cause of infectious mononucleosis, and worldwide, the virus is associated with nearly 200,000 annual cases of cancer, including lymphomas and stomach and nasopharyngeal cancers. Currently, there is no licensed vaccine to prevent EBV infection.

NIAID researchers and collaborators have developed a nanoparticle-based EBV vaccine that can elicit potent neutralizing antibodies in vaccinated mice and monkeys. In designing their experimental vaccine, the scientists focused on glycoprotein 350, or gp350, a molecule on the surface of EBV that helps the virus attach to certain immune cells and is thought to be a key target for antibodies capable of preventing virus infection. Building on previous efforts to design gp350-based vaccines, the researchers used structure-based design to target the cell-binding portion of gp350. Compared with previous vaccine designs, their nanoparticle-based vaccine induced up to 100-fold higher levels of neutralizing antibodies in mice.

The scientists’ findings suggest that using structure-based vaccine design and incorporating nanoparticles to deliver a viral protein that prompts an immune response may be a promising approach for developing a vaccine to prevent EBV infection in humans.


Cells infected with Epstein-Barr virus.
Credit: National Cancer Institute
 

Predicting Tuberculosis Treatment Outcomes

With multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant TB on the rise worldwide, new biomarkers are needed to determine the effectiveness of treatment regimens and assess the risk of disease relapse. Sputum cultures are widely used to detect TB-causing bacteria in mucus from the lungs, but they can be unreliable and are limited in their predictive ability.

NIAID researchers and colleagues showed that two medical imaging techniques, positron emission tomography (PET) and computed tomography (CT), potentially could be used in combination to predict the effectiveness of TB drug regimens. PET scans use a radioactive tracer to show how organs and tissues are functioning, while CT scans use special X-ray equipment to make cross-sectional pictures of the body. Combined PET/CT scans give more detailed pictures of areas inside the body than either scan alone.

The investigators analyzed scans from 28 patients with MDR TB enrolled in a clinical treatment trial, inspecting features such as the volume of diseased lung and active areas of inflammation. The researchers observed that early changes in PET/CT scans two months into the course of treatment could more accurately predict patient outcomes at 30 months than sputum cultures.

Scientists will next need to confirm the utility of PET/CT imaging in a larger group of people with TB. Although the expense of the technology may prevent its widespread use in routine patient care, it could be used in clinical trials of investigational drugs or diagnostics for TB, potentially shortening the duration of a trial and saving resources.


A CT scan showing a TB patient’s response to an antibiotic drug regimen.
Credit: NIAID
 

Developing Ebola Treatments

The 2014 Ebola virus outbreak in West Africa has caused more cases and fatalities than all previous Ebola outbreaks combined. Currently, there are no approved treatments for Ebola virus disease. In 2015, NIAID-supported researchers reported key two advances toward the development of antiviral drugs targeting Ebola.

In one study, investigators showed that short interfering RNAs (siRNAs) adapted to target the Makona outbreak strain of Ebola virus protected rhesus monkeys against lethal Ebola virus challenge. Although all infected animals showed evidence of advanced disease, siRNA-treated animals had milder clinical features. The treated animals fully recovered, while those untreated succumbed to the disease.

A separate study identified a viral component that is important for Ebola virus replication and could serve as a potential target for antiviral therapy. During an early stage of Ebola virus replication, two Ebola proteins, VP35 and NP, interact and form a complex. Researchers identified the VP35 peptide, which is the minimum portion of VP35 needed to bind NP. They then characterized the NP-VP35 peptide complex and determined the role of the VP35 peptide in viral RNA synthesis, a key part of the replication process.

Further development of these and other potential Ebola treatment strategies may lead to development of countermeasures against future outbreaks.


A CT scan showing a TB patient’s response to an antibiotic drug regimen.
Credit: NIAID
Content last reviewed on August 11, 2016