Hantavirus: First human antibody to effectively neutralize discovered

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An international research team has discovered the first human antibody capable of effectively neutralizing two types of hantavirus in animal models, according to a study published online March 16 in Science Translational Medicine. Based on their early results, the antibody appears to be a promising candidate for developing a “pan-hantavirus” therapy to protect against outbreaks caused by several known or emerging hantavirus types.

Hantavirus particles exhibit a characteristic square surface “web” composed of building blocks that contain the envelope glycoproteins Gn and Gc. These glycoproteins, the only targets of neutralizing antibodies, control the ability of the virus to penetrate cells. The figure shows a schematic representation of the glycoproteins and how they are organized within the virus particle (top, front view; bottom, side view). Key: Gn, green; Gn cover loop, purple; Gc domain I, red; Gc domain II, yellow; Gc domain III, blue; Gc fusion loops, orange. The approximate position of the viral membrane is indicated by a black line.
Image/photo courtesy USAMRIID

Collectively, hantaviruses cause approximately 50,000 serious and often fatal infections worldwide each year. While humans are usually infected through contact with rodents, viruses can also be transmitted through direct person-to-person contact. There are currently no approved treatments available to treat hantavirus infection.

Rodent-borne hantaviruses are grouped into two distinct viral families, commonly referred to as “Old World” and “New World” hantaviruses, and cause two types of disease. Hemorrhagic fever with renal syndrome (HFRS) is caused by Old World viruses found mainly in Europe and Asia, while New World viruses cause hantavirus cardiopulmonary syndrome (HCPS) and are found generally in North and South America.

In this article, scientists describe the isolation of several human monoclonal antibodies, or mAbs, from a patient in Sweden who survived infection with the Puumala virus, which causes HFSR in humans. Through initial screening in cell culture, the team identified several mAbs that effectively neutralized both Old World and New World hantaviruses.

Next, the researchers tested an mAb that looked particularly promising in two different animal models. They challenged hamsters and voles with Puumala virus (Old World) and Andes virus (New World), and found that this single antibody offered broad protection to both groups.

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“This is the first monoclonal antibody to demonstrate cross-protective efficacy against divergent Old and New World hantaviruses,” said Andrew S. Herbert, Ph.D., Immunology Branch Chief virus at the US Army Medical Research Institute of Infectious Diseases (USAMRIID). Herbert was co-lead author of the paper and led the Andes virus challenge studies at the Institute.

According to the authors, the hantavirus epidemics in Sweden, Argentina and the United States over the past two decades highlight the public health risks displayed by these viruses. The frequency of these epidemics and other emerging diseases is expected to increase along with the loss of animal habitat and climate change.

“The lack of FDA-approved or emergency-licensed vaccines and therapeutics represents a critical gap in our preparedness for a public health emergency caused by a large hantavirus outbreak,” they conclude.