The "Secret Weapon" of Virus-Neutralizing Antibodies

A new study in mice has explored why certain antibodies are highly effective in protecting the body against debilitating viruses like chikungunya.

The findings may help guide the engineering of therapeutic antibodies with greater potency against emerging viruses. Chikungunya is a mosquito-borne virus originating in Africa that has more recently spread into the Caribbean and South and Central America, causing more than 1.7 million cases – a rising incidence that has also been linked to climate change.

Although the infection is rarely fatal, symptoms can include fever, rash, muscle inflammation and debilitating multi-joint arthritis that can last from weeks to years. Currently, there are no licensed vaccines or therapies to combat the disease.

“Many emerging viruses have no treatments. Antibodies against a virus are attractive candidate therapies because of their specificity, generally excellent track record of safety (many antibodies are drugs), and established path for clinical and regulatory development. Notwithstanding these points, it is still critical to test which antibodies have the greatest potency in vivo (initially in animal models) and determine the correlates and basis for their protective activity.” -Michael Diamond, professor of medicine, molecular microbiology, pathology and immunology at Washington University School of Medicine in St Louis.

Despite multiple studies in mice and nonhuman primates – which highlight the protective effect of strongly neutralizing antibodies against chikungunya infection – scientists still seek to understand just how the immune system responds to confer protection. Here, Julie Fox and colleagues examined antibodies against chikungunya in a mouse model of chikungunya-induced arthritis.

They found that a certain portion of the antibodies – the Fc protein – played a major role in protection. Mice treated with activated Fc portions of the antibodies effectively cleared the virus and exhibited reduced joint swelling, compared to mice lacking activation of the Fc protein receptor.

“We have established the Fc region of the antibody (which mediates effector function) has a key role in clearing virus from infected cells. This will likely be important for many viruses that display their viral proteins on the surface of infected cells and can be targets of antibodies and their effector functions. This information also can help optimize the therapeutic activity of anti-CHIKV and other antibodies, as we define which immune cells and which functions contribute to protection. Antibodies then can be engineered with specific glycans or sequences to optimize these activities and potentially improve potency.”

Furthermore, Fox et al. discovered that the Fc-mediated control of chikungunya infection was associated with an accelerated influx of monocytes (a type of innate immune cell). In the absence of monocytes, antibodies against chikungunya failed to protect against the disease in mice, resulting in severe chikungunya-induced symptoms.

This article has been republished from materials provided by the journal Science Immunology. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Fox et al. (2019). Optimal therapeutic activity of monoclonal antibodies against chikungunya virus requires Fc-FcγR interaction on monocytes. Science Immunology.