Selected NIAID Research Advances of 2014

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 and immune-mediated diseases.

This slideshow highlights notable scientific advances made by NIAID laboratories and NIAID-funded researchers at domestic and international institutions during fiscal year 2014. Some advances brought us closer to much-needed vaccines and treatments for Ebola, HIV, and influenza. Others expanded our knowledge of rare conditions such as prion diseases and immunodeficiency disorders. All are representative of how public investment in biomedical research can advance science and benefit human health.

For more than 60 years, NIAID research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and abroad. Through our sustained commitment to basic and clinical research, we will continue to address the health challenges facing our nation and the world for years to come.

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

Developing an Ebola Vaccine

The historic outbreak of Ebola virus disease in West Africa in 2014 accelerated efforts to develop a preventative vaccine. Scientists at NIAID’s Vaccine Research Center and Okairos, a biotechnology company acquired by GlaxoSmithKline, have developed a candidate Ebola vaccine that provided rapid and durable protection against Ebola virus infection in monkeys. The experimental vaccine, the product of knowledge gained from three earlier NIAID-developed investigational Ebola vaccines, is made from two Ebola virus gene segments incorporated into a chimpanzee cold virus vector called ChAd3.

A single shot of ChAd3 Ebola vaccine protected four macaque monkeys exposed to Ebola virus five weeks after vaccination. Two of four animals were protected when challenged with Ebola virus 10 months after vaccination, suggesting that the shot's protective effects wane over time. However, giving monkeys a booster vaccine increased levels of durable protection against Ebola virus. Researchers vaccinated four macaques first with the ChAd3 Ebola vaccine, then eight weeks later with a vaccine that used a different vector. Ten months after the initial inoculation, all four animals were fully protected against infection with high doses of Ebola virus.

The ChAd3 Ebola vaccine used in this animal study is the same vaccine that was tested in late 2014 in an early-stage human clinical trial at the NIH Clinical Center in Bethesda, Maryland. Interim results from the trial showed that the vaccine was safe and well-tolerated in all 20 volunteers who received it, and immune responses were comparable to those observed in protected macaques.

Advancing Toward Lasting HIV Prevention

A major route of HIV infection is through unprotected sex with an infected person. NIH-funded researchers developed a new mouse model that can mimic this common infection route. The new model is valuable for testing preventative therapies and is less expensive than monkey models.

The researchers used this mouse model to test a therapy called vectored immunoprophylaxis, or VIP. VIP works by using a harmless virus, called a vector, as a delivery vehicle to introduce antibody genes that protect against HIV. The researchers used VIP to deliver genes for antibodies called VRC01 and VRC07. These antibodies are broadly neutralizing against many strains of HIV and were originally discovered at the NIAID Vaccine Research Center.

To test the potential of VIP in preventing HIV infection, mice first received VIP containing VRC01 or VRC07 antibody genes. Afterwards, they were challenged weekly with HIV using the new infection model. Most mice receiving VRC01 VIP and all mice receiving VRC07 VIP were protected from HIV infection. In contrast, most untreated mice became infected with HIV, often after fewer exposures to the virus.

The researchers confirmed in mice that VIP produces protective antibodies at vaginal surfaces where HIV may enter the body. Much more research is needed to determine whether a similar strategy could work in people.

HIV budding from an immune cell.
Credit: CDC

Simplifying Prion Disease Detection

Creutzfeldt-Jakob disease (CJD), a prion disease, is an incurable, transmissible, and ultimately fatal neurodegenerative disorder. Prion diseases occur when normally harmless prion proteins become abnormal and gather in clusters, resulting in sponge-like holes and other damage in the brain.

A definitive CJD diagnosis requires taking a biopsy, or small sample, of brain tissue. NIH researchers and their collaborators from the University of Verona developed a less invasive and quicker test to diagnose CJD. The new technique is performed through the nasal cavity, using a brush to collect olfactory neurons connected to the brain. From a sample of 31 CJD patients, the new test correctly diagnosed 30 patients and also accurately showed negative results for all 43 non-CJD patients.

An easy-to-use diagnostic test will allow doctors to clearly differentiate CJD from other brain diseases, enhance the development of early treatments, and prevent the spread of CJD, which can occur through contaminated surgical instruments or exposure to cattle with prion disease. With additional validation, this test has potential for use in clinical and agricultural settings.

The noninvasive procedure involves gently brushing the inside of the nose to collect olfactory neurons connected to the brain.
Credit: NIAID

Improving PrEP to Reduce New HIV Infections

Pre-exposure prophylaxis (PrEP) is an approach to HIV prevention in which an antiretroviral pill is taken by people who are at high risk of becoming infected. PrEP is most effective when people take the pill daily, but adherence to this regimen has been an impediment to its efficacy and widespread adoption. By reducing the frequency of PrEP, researchers are seeking ways to optimize its use.

NIH-funded researchers and scientists from the pharmaceutical company GlaxoSmithKline examined a PrEP candidate called GSK744, also known as Cabotegravir or CAB, in a monkey model of HIV infection. CAB has attractive features, including similarity to an FDA-approved pill used to treat HIV infection, formulation as a long-acting injectable drug, and encouraging safety results from initial tests in people.

The researchers tested the ability of CAB to protect against viral infection over a 20-week period. The drug was given one week prior to weekly viral challenges and then given a second time, four weeks after the first dose. All monkeys receiving CAB were protected from infection, whereas all untreated monkeys became infected. Importantly, the drug was found in rectal and gastrointestinal tissues, sites where HIV enters the body and spreads. While more work is needed to determine efficacy in people, drugs like CAB promise to improve PrEP by decreasing adherence problems and reduce new HIV infections.

Researchers conducting experiments.
Credit: NIAID

Modeling and Predicting Responses to Influenza Vaccination

The best way to prevent influenza, or the flu, is through vaccination. However, the immune response to vaccines varies across people, with some producing higher levels of protective antibodies than others. To improve flu vaccines, scientists are studying the cause of these differences.

With the help of over 60 healthy volunteers, NIH scientists assessed the state of the immune system before and after administration of the 2009 seasonal and pandemic H1N1 flu vaccines. The researchers obtained blood samples from volunteers multiple times before and after vaccination. These samples provided many types of data for modeling, including the frequencies of different immune cell types, expression of genes, the levels of flu-specific antibodies, and the activity of antibody-producing cells.

Such data sets contain tens of thousands of measurements per person, so one of the biggest challenges was developing ways to meaningfully integrate the data to gain new insights into the response to flu vaccination. After extensive analyses, the researchers found that the frequency of a few immune cell types present before vaccination was sufficient to predict the level of flu-specific antibodies made after vaccination. If this holds true in future studies, scientists can apply this knowledge to the design of future vaccines.

The frequency of a few cell populations (colored circles) present before vaccination may be used to predict the level of antibodies (green) made after vaccination. Some people (red) respond much better to vaccination compared to others (blue).
Credit: NIH

Detecting HIV-Neutralizing Antibodies

NIAID researchers are advancing HIV vaccine design by studying broadly neutralizing antibodies (bnAbs), which work against many HIV strains. In 2010, scientists at NIAID’s Vaccine Research Center (VRC) identified bnAbs that neutralize up to 90 percent of known HIV strains. These bnAbs, called VRC01 class antibodies, bind to one of the few parts of the HIV surface that remains similar across HIV variants.

Identifying VRC01 class antibodies in the blood of HIV-infected people presents a challenge. By using DNA-sequencing techniques, scientists can obtain detailed information about the genes that produce all the antibodies created by a person’s immune system. However, it is difficult to predict an antibody’s function based on DNA sequence alone. Although VRC01 class antibodies share similar features, their sequences differ by up to 50 percent.

NIAID researchers described a new bioinformatics approach that allows them to identify VRC01 class antibodies based on sequencing data. By using this technique, they found 10 VRC01 class antibodies in the blood of an HIV-positive donor. The ability to identify VRC01 class antibodies by sequencing patient samples promises to expedite the detection of these bnAbs in both HIV-positive people and recipients of experimental HIV vaccines.

Blood bags used to study HIV infection.
Credit: NIAID

Understanding How Antibiotics Alter Microbial Communities

Treatment with some antibiotics can alter the community of microbes that naturally colonize the gut, creating an environment in which certain pathogens can flourish and cause disease. One such pathogen, the bacterium Clostridium difficile, is the leading cause of antibiotic-associated diarrhea in the United States, causing over 450,000 infections and 14,000 deaths each year.

An NIAID-funded study showed that giving mice antibiotics changed the composition of the microbial communities in the animals’ guts in a way that allowed C. difficile overgrowth. The researchers also found that levels of certain chemicals in the mouse gut, called metabolites, changed after antibiotic treatment. To further test this concept, the scientists harvested the intestinal contents of mice and added C. difficile. The pathogen grew well only in the intestinal contents of antibiotic-treated mice, suggesting that changes in specific metabolites can create a more favorable environment for C. difficile growth. These findings establish a link between antibiotic treatment and susceptibility to C. difficile infection.

Overall, the results demonstrate that antibiotics have a profound effect on the microbial communities in the gut, resulting in an environment that favors growth of pathogens such as C. difficile. Understanding the links between antibiotics, gut microbes, and metabolic function promises to aid development of new strategies to diagnose and treat C. difficile infections and other diseases.

A Clostridium difficile bacterium.
Credit: CDC

Improving Outcomes for Infants With SCID

Results from an NIAID-funded study show that early transplantation of blood-forming stem cells is a highly effective treatment for infants with severe combined immunodeficiency (SCID), a group of rare inherited immune system disorders. SCID is caused by defects in genes involved in the development and function of infection-fighting T and B cells. Infants with SCID appear healthy at birth but are highly susceptible to infections. If untreated, the condition is fatal, usually within the first year of life.

NIAID-supported investigators analyzed data from 240 SCID infants who received transplants at clinical centers across North America between 2000 and 2009. Their findings indicate that early transplantation and absence of infection are critical to achieving excellent transplant outcomes for infants with SCID. Infants who received transplants within the first 3.5 months of life had the best outcomes, regardless of donor type, with 94 percent still alive five years after transplant. Five-year survival rates for infants of any age who did not have infection at time of transplant also were high.

The findings highlight the positive impact of treating SCID early in life and pave the way for work to identify optimal stem cell transplant procedures for infants with this serious disorder. They also suggest that widespread use of newborn screening tests to detect SCID before symptoms appear is warranted to ensure that affected infants receive life-saving transplants. By late 2014, more than half of all states had implemented newborn screening for SCID, with many more planning to do so.

Blood is collected from a newborn for screening.
Credit: U.S. Air Force photo/Staff Sgt. Eric T. Sheler

Boosting the Effectiveness of Flu Antibodies

Seasonal flu vaccines are regularly tailored to the flu strains anticipated to circulate in a particular year. A universal flu vaccine, in theory, could neutralize most or all influenza virus strains, eliminating the need for seasonal vaccination.

Universal flu vaccine candidates are designed to elicit broadly neutralizing antibodies (bnAbs), and research to understand how bnAbs are made and how they work is underway. The majority of flu vaccine-elicited antibodies target a viral protein called hemagglutinin (HA), which protrudes from the viral surface with a “stem” and “head” structure. Non-bnAbs, like those produced after immunization with seasonal vaccines, target the varying head portion of HA, whereas bnAbs target the more conserved stem region.

NIAID-funded researchers identified important differences between bnAbs and non-bnAbs. Using a mouse model that mimics the human immune system, they discovered that bnAbs must interact with a host protein called Fc-gamma receptor (FcγR) to prevent flu infection. Non-bnAbs do not require FcγR to work effectively. This distinction suggests that improving the interaction between bnAbs and FcγR may offer better flu protection, information that is useful toward building a universal flu vaccine.

3D print of influenza virus. The virus surface (yellow) is covered with proteins called hemagglutinin (blue) and neuraminidase (red) that enable the virus to enter and infect human cells.
Credit: NIH 3D Print Exchange

Tracking the Evolution of HIV and Natural Immunity

Scientists previously have identified a portion of HIV’s outer coat, called V1V2, as a promising vaccine target. In some HIV-infected people, antibodies that target this area develop naturally and are broadly neutralizing—capable of blocking entry of many different HIV strains. While these antibodies could provide ideal templates for vaccine design, scientists do not know how they develop.

Researchers from the NIAID Vaccine Research Center and their colleagues, including those from the Centre for the AIDS Programme of Research in South Africa (CAPRISA), identified a V1V2 broadly neutralizing antibody (bnAb) from a CAPRISA patient. Equipped with blood samples spanning four years after infection, the scientists were able to track the evolution of both the antibody, called CAP256-VRC26, and HIV over the course of the patient’s infection.

The researchers discovered that a structural feature unique to V1V2 bnAbs forms during an early stage of antibody development. This information may help scientists more easily identify the cells likely to produce bnAbs. The researchers also found that this particular bnAb becomes broadly neutralizing within months of initial infection, while previously described bnAbs require years to mature. This work provides further support for V1V2 bnAbs as promising templates for HIV vaccine design.

Vaccine Research Center scientists harvesting cells.
Credit: NIAID

Identifying Treatments for Ebola

By the end of 2014, the Ebola outbreak in West Africa had resulted in over 20,000 confirmed cases with over 7,900 deaths worldwide, according to World Health Organization estimates. Currently, there are no approved treatments for Ebola virus disease. However, promising potential therapies are under development in addition to improved healthcare, public health efforts, and vaccine development efforts.

ZMapp is an Ebola treatment candidate consisting of Ebola-specific antibodies originally generated from mice and later optimized for the human immune system. Previously untested in people, the cocktail was used in a few cases during the 2014 outbreak before supply was exhausted. During the outbreak, investigators including NIAID-funded researchers continued optimizing ZMapp in animal models. Importantly, the researchers showed that ZMapp could successfully treat Ebola-infected macaques, a monkey model for human disease. NIAID is currently funding preclinical safety studies and assay development in support of future human clinical trials.

Ebola virus belongs to the Filoviridae family, which includes other viruses that also cause severe hemorrhagic fevers in people, such as Marburg virus. An antiviral drug that could target all filoviruses would provide a valuable and cost-effective strategy to treat current and future outbreaks.

NIAID-funded researchers developed a broad-spectrum antiviral drug called BCX4430. In laboratory tests of human cells, the drug could inhibit infection by different types of filoviruses. In rodent and monkey studies, the drug offered protection after infection with Ebola or Marburg viruses, and importantly, it also was effective in treating Marburg-infected macaques. NIAID is currently supporting Phase I evaluation of BCX4430. Future development of BCX4430 may provide an unprecedented countermeasure against filovirus outbreaks.

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

Advancing Treatment of HIV-Infected Babies

Although treatments for HIV-infected pregnant women can greatly lower the risk of mother-to-child HIV transmission, these strategies have not been universally adopted. Globally, an estimated 200,000 to 300,000 babies are born with HIV each year, according to the World Health Organization.

NIAID-funded researchers reported the first case of an HIV-infected baby who appeared to be “functionally cured,” meaning the child had no detectable virus and no signs of disease for an extended time period after anti-HIV therapy was stopped. The child was born in 2010 in Mississippi to an HIV-infected mother who had not received prenatal care. Doctors started the baby on a triple anti-HIV drug combination at 30 hours of age—a treatment regimen involving more drugs given weeks earlier than usual. At one month of age, the infant no longer had HIV detectable in her blood. At 18 months of age, the child fell out of medical care and stopped taking the drugs. When the child returned to the clinic five months later, doctors did not detect any virus in the blood. HIV remained undetectable in the child in the absence of treatment for a total of 27 months. The virus then reappeared, and the child was put back on anti-HIV therapy.

An ongoing NIH-funded clinical trial aims to build on the Mississippi baby findings. This trial is exploring whether giving anti-HIV therapy soon after birth to infants who became infected with HIV in the womb leads to undetectable levels of the virus, thereby enabling the children eventually to stop treatment for an extended time period.

A baby holds her father's hand.
Credit: Pixabay

Understanding How Effective HIV Antibodies Evolve

A significant challenge to developing an effective HIV vaccine is the presence of multiple, diverse variants of the virus. Because antibodies are highly specific to the viruses they neutralize, it is difficult for researchers to design a vaccine that can target most HIV strains effectively.

Broadly neutralizing antibodies (bnAbs) are promising models for the development of an HIV vaccine. Known bnAbs, which typically require multiple changes to progress from the original antibody into a bnAb, are difficult to recreate using traditional vaccine approaches. NIAID-funded researchers, along with scientists at NIAID’s Vaccine Research Center, discovered a new model for how bnAbs are generated in the body.

The team tracked a bnAb called CH103 that was isolated from an HIV-infected individual. Surprisingly, the team found that the conversion of CH103 into a bnAb required cooperation with another antibody called CH235. In the presence of CH235, HIV variants that resisted CH235 had a survival advantage and persisted. However, these same HIV variants also remained sensitive to early versions of CH103, driving the maturation of CH103 into a bnAb.

In the future, researchers can screen for additional “helper” antibodies that may be required for the development of bnAbs, as well as incorporate “helper” models into new strategies to recreate bnAbs in the laboratory and in recipients of experimental HIV vaccines.

Atomic structure of the antibody CH103 binding to the gp120 region of HIV.
Credit: NIAID

Advancing Toward a Universal Flu Vaccine

Seasonal flu vaccines elicit antibodies that target the viral surface protein hemagglutinin (HA), preventing the influenza virus from entering and infecting cells. When the vaccine-targeted viruses change, the antibodies may no longer “fit.” Thus, seasonal flu vaccines are updated and tailored to the flu strains predicted to circulate each year. For years, scientists have been pursuing the development of a universal flu vaccine that could neutralize most or all influenza strains.

NIAID-funded investigators found that volunteers immunized with seasonal flu vaccines primarily developed antibodies directed against the highly variable head region of HA. The HA head typically undergoes genetic changes as flu viruses evolve, making the antibodies produced against one strain ineffective against another strain.

In contrast, immunization with HA from the avian influenza virus H5N1 increased production of antibodies against the HA stem region, which varies little among different flu viruses. Volunteers had not been previously exposed to H5N1 virus, and the scientists suspect that their immune systems' unfamiliarity with H5N1 may have contributed to the boost in stem-specific antibodies.

The findings suggest a potential strategy in which vaccines directed against flu viruses not currently circulating in humans, such as H5N1, could be used to increase production of antibodies that protect against a broad array of flu viruses.

Influenza virus particles. Surface proteins on the virus particles are in black.
Credit: NIAID

Developing New Treatments for HIV/AIDS

Antiretroviral drugs for HIV infection target the replicating virus. HIV-neutralizing antibodies, which affect virus-infected cells as well as the virus itself, offer the potential for development of new treatment strategies.

NIAID scientists reported that treating monkeys infected with simian-human immunodeficiency virus (SHIV), a virus similar to HIV, with neutralizing antibodies reduced blood levels of the virus, or viral load. Administering two antibodies to two symptom-free monkeys with long-term SHIV infections quickly reduced their viral loads to undetectable levels. Viral loads remained low for three to five weeks, then rose. A second antibody infusion reduced viral load to undetectable levels for 4 to 28 days. When virus reappeared, strains in one monkey were antibody-resistant. The researchers evaluated the same antibody pair in three chronically SHIV-infected monkeys that were experiencing AIDS-like symptoms. Infusion provided only modest benefit but did not generate resistance.

Results from a separate study conducted by NIAID grantees supported the NIAID scientists' findings. In this study, scientists found that antibody infusions reduced viral loads to undetectable levels in 16 of 18 monkeys for an average of 56 days. Taken together, the results suggest that antibody therapy, alone or in combination with conventional drugs, could be an effective treatment for people with HIV.

An HIV-infected immune cell.
Credit: NIAID

Designing a Vaccine to Prevent Respiratory Illness in Children

Respiratory syncytial virus (RSV) is the most common cause of severe respiratory illness among children in the United States. No vaccine is currently available to prevent this common childhood infection, although an antibody called palivizumab can protect high-risk children from developing severe RSV illness. Palivizumab attaches to a viral surface protein called F, which helps the virus fuse with its target cell. During fusion, the F protein rearranges from an unstable pre-fusion shape into a stable post-fusion shape.

Scientists at NIAID’s Vaccine Research Center (VRC) developed a vaccine containing a pre-fusion stabilized RSV F that elicits high levels of RSV-specific antibodies in mice and monkeys. Previously, the scientists had reported the three-dimensional structure of pre-fusion F bound to a human RSV antibody, spotlighting a key area of the protein that is highly sensitive to neutralizing antibodies and is not present in the post-fusion structure. Building on this work, they set out to stabilize the pre-fusion F structure to display the neutralization-sensitive site.

The scientists engineered hundreds of variants of the F protein, some of which remained stable in the desired pre-fusion structure. When mice and monkeys were immunized with the stabilized pre-fusion F, they produced neutralizing antibodies at levels well above those needed to protect against infection. Based on these results, the VRC scientists are developing a candidate RSV vaccine to test in humans. In addition, they are using structural information to inform the design of vaccines against other viral infections, including HIV.

Doctor examining baby.
Credit: iStockphoto

Tracking Ebola Genomes and Outbreak Origin in West Africa

The 2014 Ebola outbreak in West Africa is the largest outbreak of the disease since it was discovered in 1976. There are five known strains of Ebola virus, also called EBOV, and the West Africa outbreak has been spread by one strain, the Zaire ebolavirus. Researchers have studied the genetic sequences, or genomes, of EBOV to understand its origin, transmission, and other details useful for diagnosis, treatment, and development of vaccines.

NIH-funded researchers obtained EBOV samples from patients at the Kenema Government Hospital in Sierra Leone, which confirmed the first Ebola case in the country in late May. The team generated 99 EBOV genomes from 78 patients, capturing over 70 percent of Ebola patients diagnosed in Sierra Leone from May to June.

The researchers compared the new EBOV genomes to each other and to samples collected from previous outbreaks. Their work suggested that the 2014 outbreak likely began when an unidentified animal host carrying the virus infected a human. The disease then spread from human to human. Furthermore, the team identified many changes or mutations in the Ebola genome. Understanding which parts of the viruses change frequently and which stay the same is important for development of effective Ebola diagnostics and vaccines. Ongoing research studies, alongside improved healthcare and public health efforts, will enable the international community to eradicate the current outbreak and develop vaccines to prevent future outbreaks.

Colorized scanning electron micrograph of Ebola virus particles (green) attached and budding from an infected cell (orange).
Credit: NIAID

Monitoring Reactivation of Latent HIV

Despite antiretroviral therapy (ART), HIV remains dormant, or latent, in a very small fraction of immune cells. If ART is interrupted or stopped, latent HIV can begin replicating and spreading again, a phenomenon that presents a major barrier to an HIV cure. Laboratory models of latent HIV-infected cells have suggested that certain drugs, called latency-reversing agents (LRAs), may reactivate the latent virus and render the infected cells vulnerable to destruction.

NIAID-funded scientists developed a new technique to test the effectiveness of LRAs in immune cells taken directly from HIV-infected people on ART. Using this test, the researchers aimed to compare a variety of candidate LRAs and determine which were best at reactivating the latent virus. Surprisingly, they found that none of the LRAs tested reactivated HIV in the patient-derived cells.

The findings suggest that individual LRAs are unlikely to drive reactivation and elimination of latent HIV reservoirs. In addition, they indicate that results from laboratory models of latent HIV-infected cells may not be representative of what actually happens in cells from HIV-infected people. The new technique developed by the researchers will allow them to test other strategies, such as the use of combinations of LRAs, for reactivation of HIV in patient-derived cells.

An HIV-infected T cell.
Credit: NIAID

Identifying Drug-Resistant Malaria Parasites

Malaria is caused by Plasmodium parasites, and according to the World Health Organization, approximately 198 million malaria cases occurred in 2013. While malaria death rates have fallen approximately 47 percent since 2000, resistance to artemisinin-based antimalarial drugs, the standard treatment for the disease, has emerged in Cambodia and other parts of Southeast Asia.

To monitor and prevent the spread of artemisinin-resistant parasites, researchers must be able to identify them accurately and quickly. NIAID researchers and their colleagues identified the first known genetic marker of artemisinin resistance in malaria parasites. They selected a laboratory strain of parasites to resist artemisinin and discovered that these parasites had a mutant version of a gene called K13-propeller. Then, they screened parasites collected between 2001 and 2012 from 10 provinces in Cambodia and found that parasites with the mutant gene had become more frequent in drug-resistant areas.

The researchers also examined clinical data from 150 Cambodian patients who were treated with artemisinin and found that patients with harder-to-clear malaria were infected by parasites with a mutant K13-propeller gene. The ability to easily identify artemisinin-resistant parasites is an important step in preventing its spread to other malaria-endemic regions such as Africa. Current efforts investigating the role of the K13-propeller gene will offer clues for developing new malaria treatments.

A home visit in Cambodia to assess a patient with malaria.
Credit: NIAID

Discovering a New Target for HIV Prevention and Treatment

An important goal of HIV research is to identify which part of the virus to target with vaccines and treatments. Recently, an NIAID-led team of scientists discovered a new vulnerable site on the viral spike—the part of HIV that binds to the cells it infects—that a vaccine or treatment could exploit. The researchers identified the site by studying an antibody found in an HIV-infected person. This antibody, called 35O22, prevents 62 percent of known HIV strains from infecting cells in the laboratory and is extremely potent, meaning even a relatively small amount of it can neutralize the virus.

The scientists found that 35O22-like antibodies were common in a group of HIV-infected people whose blood contained antibodies that neutralize a multitude of HIV strains, called broadly neutralizing antibodies (bnAbs). The HIV strains that 35O22 neutralizes complement strains neutralized by other bnAbs, suggesting that eliciting 35O22 in combination with other bnAbs in a vaccine or a prevention or treatment regimen may neutralize most HIV strains.

The research team also noted that 35O22 binds only to forms of the viral spike that closely resemble those that naturally appear on HIV, a finding that has direct implications for HIV vaccine design. A vaccine that elicits 35O22-like antibodies likely would need to closely mimic the natural shape of the entire viral spike. This would require a different approach than that used in many previous experimental HIV vaccines, which have included only parts of the spike.

HIV virus infecting cell.
Credit: iStockphoto