As recent news stories attest, measles is one of the most infectious diseases on Earth — and it affects more than just humans. Nonhuman primates are also at risk.

Although the CNPRC requires all employees and visitors to obtain measles vaccination or show proof of immunity, the center’s animals could still be at risk of outside contamination. Before 1996, the only vaccination protocols for nonhuman primates were based on protocols developed for humans, but these were not cost-effective, and primate facilities needed a better option.

This is why, since 1996, Kari Christe, DVM, has worked to test the safest and most efficient way to vaccinate the entire CNPRC rhesus macaque monkey colony. Her team’s work is also providing information to help other facilities make informed decisions on how to protect their animal colonies.

Christe and her veterinary team have made significant progress. Before this research began, many primate facilities did not have the resources to vaccinate their monkeys. But Christe and team have shown it is possible to protect rhesus macaques from measles in a cost-effective fashion using only half the recommended dose of a specific type of vaccine — the measles and canine distemper vaccine — in comparison to the measles, mumps and rubella vaccine used in humans. The new strategy will save research facilities, zoos and conservation organizations at least $3 per animal (there are nearly 4,000 animals at the CNPRC), based on the most recent estimates. 

With safer and more cost-effective vaccine protocols than ever before, Christe and CNPRC veterinarians are working their way toward protecting all nonhuman primates from measles at their facility and beyond. And this means those same animals will be able to participate in NPRC research studies focused on improving health for humans and animals alike.

Reviewed: June 2020

Ebola virus is a continuing threat in Central and West Africa, with an outbreak currently taking place in the Democratic Republic of Congo. But the factors that determine who is most susceptible to Ebola infection are still a mystery.

Now,  researchers at Texas Biomedical Research Institute, home to the Southwest National Primate Research Center —in collaboration with the University of Iowa—are investigating how malaria infections could impact people exposed to Ebola virus, since both diseases are common and recurring in the Congo.

Other co-infections are known to impact each other’s outcome. For example, patients infected with HIV-1, a virus that causes AIDS, are more susceptible to tuberculosis infection.

“A significant number of people entering Ebola Virus Treatment Units during the 2014-2016 West African outbreak were infected with both the malarial parasites, Plasmodium falciparum, and Ebola virus,” explained Professor Wendy Maury, PhD, the lead investigator at the University of Iowa.

The hypothesis is that people with an acute (active and recent) malarial infection, where the body’s immune response is already ramped up, have a greater chance of surviving Ebola infection. However, if people have chronic malaria, then they are hypothesized to be more susceptible to Ebola.

The researchers will begin by taking white blood cells from infected mice and studying them to determine what role they may play in dual malaria/Ebola infection. Knowing if the hypothesis is supported might change how doctors design therapies for Ebola in areas where both diseases are present, perhaps paving the way for more tailored therapeutics.

SNPRC’S part in the study will be a two-year process. The next step may involve testing in a higher-level animal model, such as nonhuman primates.

Photo credit: National Institute of Allergy and Infectious Diseases

You may want to think twice before sharing a bite of spare food with animals you encounter in public places. That is, unless you’re willing to risk a staph infection.

Staphylococcus aureus (S. aureus) is a bacterium that causes a wide range of infections, such as skin and soft tissue infections (SSTI), bone, joint and implant infections, pneumonia and more. Both penicillin and methicillin have been used to fight S. aureus, but strains resistant to all types of treatment have continued to emerge. Now, methicillin-resistant S. aureus (MRSA) has become a serious international problem.

In a hospital setting, MRSA can be deadly; in fact, it caused 11,000 deaths in hospitals in the U.S. in 2017. And while practices to reduce MRSA cases in hospital populations are improving, the bacterium continues to thrive in the wild in certain geographic areas. It is of particular concern in places where large numbers of humans and animals interact, including popular tourist destinations.

In a recent study, researchers at the Washington National Primate Research Center (WaNPRC) at the University of Washington (UW) along with their Nepali colleagues sampled 59 rhesus monkeys within Nepal. Those monkeys have close interactions with humans, usually at temple sites, where people offer the animals food. The researchers used a non-invasive method to collect saliva samples from the monkeys with subsequent processing at a microbiology laboratory in Nepal.

The findings were astounding. Of the macaque samples tested, 6.8% were positive for MRSA, and three of four MRSA isolates were identified as ST22 SCCmec IV. The ST22 SCCmec IV strain is normally considered a human strain, and this study suggests that humans in Nepal are sharing their strains with the wild macaque populations.

The researchers further reiterate a warning that is becoming all too well known, that even minimal contact with wild animals, especially contact with saliva or an animal bite can present significant health risks to humans.

“Some types of MRSA are found all over the world and are pandemic strains,” said lead study author Marilyn C. Roberts, PhD. “The importance should be stressed in respect to these populations of wild animals. Even feeding chipmunks or ducks human food is not a good thing. They can pick up what we have, and we can pick up what they have. Some of the infectious agents wildlife carry can be deadly.”

“Given the results of our work in Nepal, we are now extending the MRSA investigation to primates in Thailand. These efforts are part of our larger collaborative program promoting the healthy coexistence between humans and primates,” added co-author and field researcher Randall C. Kyes, PhD.

Photo Credit: Randall C. Kyes, PhD

Sometimes it really does take two. 

Scientists at Yerkes National Primate Research Center (YNPRC) at Emory University in Atlanta have discovered that a form of antibiotic resistance called “heteroresistance” is more widespread than previously thought, but attacking bacteria with combinations of antibiotics may hold the key to defeating them.

“We can think of heteroresistance as bacteria that are ‘half resistant’,” said David Weiss, PhD, director of the Emory Antibiotic Resistance Center, an associate professor of medicine (infectious diseases) and a researcher at the YNPRC. “This is because only some of the cells in the population exhibit resistance. When you take the antibiotic away, the resistant cells go back to being just a small part of the group. That’s why they’re hard to see in the tests that hospitals usually use.”

In exploring the heteroresistance phenomenon, Weiss and his colleagues examined 104 bacterial isolates, tracking multi-drug resistant superbugs. They found more than 85 percent were heteroresistant to at least two antibiotics. Weiss and his team then made their major discovery: Combining two antibiotics to which each superbug was heteroresistant proved effective at killing them. 

This occurred, they found, because the heteroresistant sub-populations were independent. If scientists grew the bacteria in the presence of one antibiotic, or knocked out resistance to that antibiotic genetically, this didn’t affect heteroresistance to any other antibiotics. 

Previously, microbiologists have thought some combinations of antibiotics might work together synergistically — one antibiotic working to weaken one part of the bacteria, while the other hits a different spot. But Weiss indicated the reasons combinations work might largely be explained by heteroresistance to multiple drugs. 

Using this knowledge, scientists are encouraged they will be able to help healthcare professionals more effectively use antibiotics to defeat bacteria that have developed resistance. 

“We’re saying: even if a strain of bacteria is classified as resistant to some antibiotics, don’t toss those drugs in the trash, they may still have some utility,” Weiss explained. “The ones targeting heteroresistance just have to be used in combination with others to do so.”

Tuberculosis is a major concern for HIV/AIDS patients, as a full one-third of all patients with the autoimmune disease die of complications from TB.

But Professor Deepak Kaushal, PhD, of the Southwest National Primate Research Center (SWNPRC) at Texas Biomedical Research Institute, says recent research could help scientists better understand how to prevent this deadly condition.

It’s known the same mechanism of HIV/AIDS which leads to the loss of immune cells (CD4 and T cells) in other parts of the body also targets the lungs, allowing latent Mycobacterium tuberculosis (Mtb) bacteria infection to become active TB. But until now, scientists weren’t sure which parts of the lungs were targeted by the immunodeficiency.

Kaushal and a team of researchers conducted a study on rhesus monkeys infected with TB and SIV (simian immunodeficiency virus), using tissue either from a humanized mouse model or from humans. The findings indicated not all T cells in the lungs are affected by HIV—only the ones embedded inside the lung tissue. T cells in the lung sacs (alveoli) where oxygen enters the blood stream were still functional.

“If our findings are validated in future testing, this leads to the potential for new therapies that would prevent the loss of these crucial T cells during HIV infection,” Kaushal said. “The idea is that fewer HIV patients would progress to TB.”

Kaushal further explained, “[This is] important to know because we can target vaccines, therapeutics and drugs to these specific T cells in the lungs.”

According to the Center for Disease Control and Prevention, more than 1.1 million people in the United States are living with an HIV infection. In the United States, Louisiana has the third-highest rate of people with an HIV infection and AIDS cases. In 2015, Louisiana-based Tulane National Primate Research Center (TNPRC) was awarded $4.2 million to study new ways to flush out and kill HIV from reservoirs in the body where the virus lurks beyond the reach of antiviral therapy options.

Current HIV treatment options can stop the disease from progressing to AIDS and knock the virus down to “undetectable” levels in the bloodstream, but they fall short of an HIV cure because they must be taken for life to keep the disease in check. That’s because HIV integrates into the genome of memory T-cells and lies dormant in reservoirs throughout the body. If a patient stops taking antivirals, HIV reawakens from these reservoirs to resume its attack on the immune system.

“The major obstacle to a cure for HIV infection is how to purge the persistent reservoir of latently infected cells,” said lead researcher Dr. Huanbin Xu, assistant professor of pathology.

Using a nonhuman primate research model of HIV, Dr. Xu plans to test standard antiviral drugs with a combination of therapies to wake up the latent virus and trigger the immune system to recognize infected cells and attack them. He will then target any remaining virus with an antibody drug conjugate, a new class of highly potent biopharmaceutical drugs. The so-called “kick and kill” approach to activate latent HIV so it’s more susceptible to targeted treatments is a promising new frontier in the search for a possible cure, Xu says.

His team will also test a new gene editing approach with a targeted delivery system for the therapy tailored to an individual’s immune system.

“So far, it’s a novel, comprehensive strategy,” Dr. Xu says.

One of the advantages of using a primate research model for the treatment is that, if it’s successful, human clinical trials could begin relatively quickly, Dr. Xu says.

Reviewed: June 2020

Working together is always better—especially when it comes to curing infectious diseases. That’s why the National Primate Research Centers (NPRCs) across the country are collaborating to tackle the deadly Zika virus with a series of studies.

In one study, researchers at the California National Primate Research Center (CNPRC) discovered that Zika may still affect fetuses that show no signs of gross microcephaly (an abnormally small head), a common symptom of the disease. Four rhesus macaques were infected with Zika on days 41, 50, 64 and 90 of gestation, respectively. The macaque infected after 41 days experienced fetal death within a week, and the fetuses of the others showed brain calcifications and reduced brain cells—all without significantly reduced brain size.

An additional study at the CNPRC recently showed that infection of the fetuses of pregnant rhesus macaques produced brain lesions like those in human newborns with Zika. The models developed from these studies at the CNPRC can be used across study locations to examine more viruses and prevention methods.

During another study, Zika data from several of the NPRCs were compiled to show that the virus may cause a greater rate of miscarriage than previously thought in humans. Of nonhuman primates infected with Zika in early pregnancy, 26 percent experienced miscarriage or stillbirth even though they showed few signs of infection. Human studies have found that about five percent of women known to be infected with Zika do not carry to term or have stillbirths. This suggests that, in areas where Zika is prevalent, the number of virus-related miscarriages and stillbirths may be underestimated.

These studies show the benefits of taking a highly collaborative approach to research, which is a priority at the NPRCs. Through close communication and teamwork, our researchers are continuing to make breakthroughs to improve worldwide health.

Reviewed: June 2020

During an epidemic in 2014, the Ebola virus claimed more than 11,000 lives in West Africa. Now, a new outbreak of the deadly disease threatens residents in eastern Democratic Republic of the Congo. While there isn’t yet a cure for Ebola, scientists at Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute recently made two discoveries that could help us understand how the virus infects the body.

In the first study, Staff Scientist Olena Shtanko, PhD studied a cellular pathway called “autophagy,” which means “self-eating.” This pathway normally occurs inside the cell and destroys invading foreign material or recycles necessary nutrients. But Dr. Shtanko’s team, working with a live Ebola virus, discovered, to their surprise, that autophagy was also active near the surface of the cell.

The Ebola virus exploits autophagy to induce another process to gain entry to the cell. That process is macropinocytosis, a poorly understood mechanism during which the cell surface remodels to form membrane extensions around virions (virus particles), eventually closing to bring them into the interior of the cell. It is as if the cell reaches out and grabs the virus, bringing it inside its membrane, where virus proteins can begin to replicate.

“We were stunned to find that Ebola virus is using autophagy regulators right at the surface of the cell,” Shtanko stated. “Knowing that these mechanisms work together, we can start finding ways to regulate them.”

Shtanko believes that drugs targeting the interplay between the two processes could potentially be developed to treat Ebola and other health conditions not associated with viruses. The regulation of the autophagy proteins could be used to fight complex diseases where macropinocytosis is disrupted, such as cancer and Alzheimer’s.

Shtanko’s commitment to fighting Ebola has spanned multiple studies. Another team she worked with discovered the interaction between an Ebola virus protein and a protein in human cells. This interaction may be a key part of replication of the killer disease in human hosts.

During the study, researchers tested whether the interaction between an Ebola virus protein called VP 30 and a host (human) protein called RBBP6 influenced the life cycle of the virus. By removing RBBP6 or flooding the cell with it, the scientists found striking results.

When RBBP6n was removed, viral replication went up exponentially compared to when the protein was present. Shtanko said this interaction is significant because if scientists can figure out the process behind this replication, they can potentially manipulate it and stop the disease progression.

Both of these discoveries represent large leaps forward in understanding the Ebola virus and treating and preventing this deadly disease.

Young macaques form an important part of our work at the NPRCs, helping us discover new ways of treating deadly diseases like tuberculosis, HIV/AIDS, Zika and more. Two researchers at Southwest NPRC at Texas Biomed recently went the extra mile to ensure these baby monkeys had a place to call their own.

https://www.kens5.com/video/news/local/eradicating-tuberculosis-with-the-help-of-macaques/273-4c1dd11c-90e8-40bf-9f51-16157308fe1f

HIV-1, the virus that causes AIDS, remains a potent global threat, especially in sub-Saharan Africa and other low-income areas. And while new treatments over the past 40 years have greatly improved the prognosis for those infected, prevention of HIV-1 infection by vaccines or immunoglobulins is not yet established.

That may change with a finding at the Southwest National Primate Research Center (SNPRC) in San Antonio, Texas. A team led by Dr. Ruth Ruprecht has shown for the first time that an antibody called Immunoglobulin M (IgM) can be effective in preventing infection in the mucosa after exposure to the virus. This is significant because an estimated 90% of new HIV-1 cases are caused through exposure in the mucosal cavities such as the lining of the sexual organs or rectum.

Rhesus monkeys at the SNPRC on the campus of the Texas Biomedical Research Institute were treated with a man-made version of IgM. Thirty minutes later, the same animals were exposed to simian-human immunodeficiency virus, a hybrid virus containing elements of the monkey and human immunodeficiency virus. Four of the six animals treated this way were fully protected against the virus.

“IgM can grab multiple particles like HIV-1 and SHIV very quickly and does not let go,” said Dr. Ruprecht. “Our study reveals for the first time the protective potential of IgM. It basically opens up a new area of research – IgM can do more than it has been given credit for.”

IgM, which had been thought by most scientists to have too short-lived a protective effect, may now lead the way to an effective barrier against HIV-1 infection.