{"id":95636,"date":"2014-09-03T08:30:55","date_gmt":"2014-09-03T12:30:55","guid":{"rendered":"https:\/\/today.uconn.edu\/?p=95636"},"modified":"2015-10-02T16:32:00","modified_gmt":"2015-10-02T20:32:00","slug":"uconn-researchers-nanoparticle-key-to-new-malaria-vaccine","status":"publish","type":"post","link":"https:\/\/today.uconn.edu\/2014\/09\/uconn-researchers-nanoparticle-key-to-new-malaria-vaccine\/","title":{"rendered":"UConn Researcher\u2019s Nanoparticle Key to New Malaria Vaccine"},"content":{"rendered":"
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\"A<\/a>
This self-assembling protein nanoparticle relies on rigid protein structures called ‘coiled coils’ (blue and green in the image) to create a stable framework upon which scientists can attach malaria parasite antigens. Early tests show that injecting the nanoparticles into the body as a vaccine initiates a strong immune system response that destroys a malarial parasite when it enters the body and before it has time to spread. (Image courtesy of Peter Burkhard)<\/figcaption><\/figure>\n<\/div>\n

A self-assembling nanoparticle designed by a UConn professor is the key component of a potent new malaria vaccine that is showing promise in early tests.<\/p>\n

For years, scientists trying to develop a malaria vaccine have been stymied by the malaria parasite\u2019s ability to transform itself and \u201chide\u201d in the liver and red blood cells of an infected person to avoid detection by the immune system.<\/p>\n

But a novel protein nanoparticle developed by Peter Burkhard, a professor in the Department of Molecular & Cell Biology, in collaboration with David Lanar, an infectious disease specialist with the Walter Reed Army Institute of Research<\/a>, has shown to be effective at getting the immune system to attack the most lethal species of malaria parasite, Plasmodium falciparum,<\/em> after it enters the body and before it has a chance to hide and aggressively spread.<\/p>\n

The key to the vaccine\u2019s success lies in the nanoparticle\u2019s perfect icosahedral symmetry (think of the pattern on a soccer ball) and ability to carry on its surface up to 60 copies of the parasite\u2019s protein. The proteins are arranged in a dense, carefully constructed cluster that the immune system perceives as a threat, prompting it to release large amounts of antibodies that can attack and kill the parasite.<\/p>\n

In tests with mice, the vaccine was 90-100 percent effective in eradicating the Plasmodium falciparum<\/em> parasite and maintaining long-term immunity over 15 months. That success rate is considerably higher than the reported success rate for RTS,S, the world\u2019s most advanced malaria vaccine candidate currently undergoing phase 3 clinical trials, which is the last stage of testing before licensing.<\/p>\n

\"Peter<\/a>
Peter Burkhard, professor of molecular and cell biology, with an image of the protein nanoparticle he designed. (Peter Morenus\/UConn Photo)<\/figcaption><\/figure>\n

\u201cBoth vaccines are similar, it\u2019s just that the density of the RTS,S protein displays is much lower than ours,\u201d says Burkhard. \u201cThe homogeneity of our vaccine is much higher, which produces a stronger immune system response. That is why we are confident that ours will be an improvement.<\/p>\n

\u201cEvery single protein chain that forms our particle displays one of the pathogen\u2019s protein molecules that are recognized by the immune system,\u201d adds Burkhard, an expert in structural biology affiliated with UConn\u2019s Institute of Materials Science. \u201cWith RTS,S, only about 14 percent of the vaccine\u2019s protein is from the malaria parasite. We are able to achieve our high density because of the design of the nanoparticle, which we control.\u201d<\/p>\n

The research was published in Malaria Journal<\/a><\/em> in 2013.<\/p>\n

The search for a malaria vaccine is one of the most important research projects in global public health. The disease is commonly transported through the bites of nighttime mosquitoes. Those infected suffer from severe fevers, chills, and a flu-like illness. In severe cases, malaria causes seizures, severe anemia, respiratory distress, and kidney failure. Each year, more than 200 million cases of malaria are reported worldwide. The World Health Organization estimated that 627,000 people died from malaria in 2012, many of them children living in sub-Saharan Africa.<\/p>\n

It took the researchers more than 10 years to finalize the precise assembly of the nanoparticle as the critical carrier of the vaccine and find the right parts of the malaria protein to trigger an effective immune response. The research was further complicated by the fact that the malaria parasite that impacts mice used in lab tests is structurally different from the one infecting humans.<\/p>\n

The scientists used a creative approach to get around the problem.<\/p>\n

\"Infectious<\/a>
Infectious disease specialist David Lanar of the Walter Reed Army Institute of Research, who is collaborating with UConn professor Peter Burkhard in pursuing a new malaria vaccine. (Photo courtesy of David Lanar)<\/figcaption><\/figure>\n

\u201cTesting the vaccine\u2019s efficacy was difficult because the parasite that causes malaria in humans only grows in humans,\u201d Lanar says. \u201cBut we developed a little trick. We took a mouse malaria parasite and put in its DNA a piece of DNA from the human malaria parasite that we wanted our vaccine to attack. That allowed us to conduct inexpensive mouse studies to test the vaccine before going to expensive human trials.\u201d<\/p>\n

The pair\u2019s research has been supported by a $2 million grant from the National Institutes of Health and $2 million from the U.S. Military Infectious Disease Research Program. A request for an additional $7 million in funding from the U.S. Army to conduct the next phase of vaccine development, including manufacturing and human trials, is pending.<\/p>\n

\u201cWe are on schedule to manufacture the vaccine for human use early next year,\u201d says Lanar. \u201cIt will take about six months to finish quality control and toxicology studies on the final product and get permission from the FDA to do human trials.\u201d<\/p>\n

Lanar says the team hopes to begin early testing in humans in 2016 and, if the results are promising, field trials in malaria endemic areas will follow in 2017. The required field trial testing could last five years or more before the vaccine is available for licensure and public use, Lanar says.<\/p>\n

Martin Edlund, CEO of Malaria No More, a New York-based nonprofit focused on fighting deaths from malaria, says, \u201cThis research presents a promising new approach to developing a malaria vaccine. Innovative work such as what\u2019s being done at the University of Connecticut puts us closer than we\u2019ve ever been to ending one of the world\u2019s oldest, costliest, and deadliest diseases.”<\/p>\n

A Switzerland-based company, Alpha-O-Peptides, founded by Burkhard, holds the patent on the self-assembling nanoparticle used in the malaria vaccine. Burkhard is also exploring other potential uses for the nanoparticle, including a vaccine that will fight animal flu and one that will help people with nicotine addiction. Professor Mazhar Khan from UConn\u2019s Department of Pathobiology is collaborating with Burkhard on the animal flu vaccine.<\/p>\n","protected":false},"excerpt":{"rendered":"

A nanoparticle designed by a UConn scientist is the key component of a promising new vaccine that could help address a global health problem.<\/p>\n","protected":false},"author":12,"featured_media":95152,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_crdt_document":"","wds_primary_category":0,"wds_primary_series":0,"wds_primary_attribution":0,"footnotes":""},"categories":[2226,88],"tags":[],"magazine-issues":[],"coauthors":[44],"class_list":["post-95636","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-clas","category-global-affairs"],"pp_statuses_selecting_workflow":false,"pp_workflow_action":"current","pp_status_selection":"publish","acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-05-03 08:07:02","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95636","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/comments?post=95636"}],"version-history":[{"count":6,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95636\/revisions"}],"predecessor-version":[{"id":104937,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/95636\/revisions\/104937"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media\/95152"}],"wp:attachment":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media?parent=95636"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/categories?post=95636"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/tags?post=95636"},{"taxonomy":"magazine-issue","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/magazine-issues?post=95636"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/coauthors?post=95636"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}