Research at WRAIR not only looks at infectious diseases and their carriers, but also on methods and technologies used in such research, from new developments to advanced applications of old technologies.
Research at WRAIR not only looks at infectious diseases and their carriers, but also on methods and technologies used in such research, from new developments to advanced applications of old technologies.
“One of those is real-time polymerase chain reactions [PCRs], which is an old method our people have enabled, doing four or six reactions at a time rather than one at a time,” according to Col. Emil Lesho, founder and director of the Multidrug-resistant Organism Repository and Surveillance Network (MRSN). “We use advanced molecular techniques, taking small amounts of DNA and enhancing it through this reaction to advance understanding of what the bugs are doing, how they affect the health of the individual, and what we can do, including policy changes to prevent infections.
“Microbiology of the future will be more like an applied chemistry and physics lab. For example, we take a chunk of bacteria, blast it apart and get a quick identification – about 200 times faster than a culture. But that doesn’t tell you what it is susceptible to. We’re also using mass spectrometry, another old technique, in that effort.”
Malaria and the Mosquito – The Long Battle
Dr. David E. Lanar, chief of the Malaria Vaccine Branch’s Department of Molecular Engineering, noted thousands of years of evolution within immunologically competent individuals have allowed the malaria parasite to “evolve several exquisite mechanisms to evade detection” by both the human immune system and medical science.
“Once a malaria parasite enters a host, it can shed or change the proteins on its surface, making recognition or binding by antibodies difficult. Also, the parasite can actively penetrate liver cells or red blood cells where it will completely change into a new cell type and thus present a complete set of new surface proteins,” he explained. “Even more frustrating is that the pathogen’s proteins have evolved to only activate a minimal immune response if they are recognized when the parasite transitions between cells.”
Microbiology lab at the KEMRI/WRAIR trial site in Kisumu-Kombewa, Kenya. Early development and clinical testing of the malaria vaccine RTS,S was part of an ongoing collaboration between GlaxoSmithKline and WRAIR. Malaria very rapidly becomes resistant to new drugs, driving researchers’ efforts to develop new drugs and vaccines. WRAIR has been successful in developing and field testing antimalarial drugs such as halofantrine, mefloquine, and tafenoquine, which provide treatment alternatives for drug-resistant strains. Darby Communications photo by John-Michael Maas
That rapidly changing picture has made the development of an effective malaria vaccine a serious challenge for scientists.
“While there has recently been some success coming from the WRAIR and GSK [GlaxoSmithKline] collaboration to make the RTS,S vaccine, the result is still only a reduction of about 50 percent fewer clinical cases of malaria in children in endemic areas of Africa. The parasites continue to grow and spread throughout the human population, causing much morbidity and mortality,” Lanar added.
“The goal now is to improve on RTS,S. Fortunately, new knowledge of how to activate the immune system with new vaccine constructs may help us succeed in teaching the body how to turn these invaders away.”
Entomology Branch Director Cmdr. Daniel Szumlas (U.S. Navy) said the insectaries at WRAIR house thousands of species of disease-carrying insects from around the world, from sand flies to Anopheles malaria mosquitos to Aedes aegypti mosquitos that transmit yellow fever and dengue, making single-facility research possible in the United States.
“There are 17 different species of sand flies. Most sand flies don’t even occur in the U.S., but everywhere else in the world, they transmit leishmaniasis and other nasty things.”
“There are 17 different species of sand flies. Most sand flies don’t even occur in the U.S., but everywhere else in the world, they transmit leishmaniasis and other nasty things,” he said, adding lab research results must be verified in the field. “If you don’t have the important vectors out there, you get good [lab] information, but it might not work the same way against Aedes aegypti or Anopheles gambiae, which is why we have the overseas labs for field testing with not only the right vector but natural populations.
“Many people can test them in the lab with insectary-reared pests, but a lot of times they have been reared for so many years, they’re not wild type anymore and actually react very differently. So it always has to go from preliminary laboratory testing to the field. And we’re adding a step in there to better control the conditions.”
The Entomology Branch also supports other departments for drug development and the malaria vaccine challenge model, as well as regular basic vector and parasite biology studies to help with any of those.