New possibilities against the HIV epidemic

Research identifies new antibodies with potent activity against virus and infected cells

The Human Immunodeficiency Virus type-1 (HIV-1) currently infects 37 million people worldwide, with an additional 2 million new infections each year. Following infection, the virus has a long period of latency, during which it multiplies without causing symptoms. HIV attacks the cells of the immune system, especially the cells called CD4+ T-lymphocytes, which are responsible for triggering the body’s response chain against infections. Thus, by suppressing the action of the immune system, the virus destroys the body’s ability to defend itself against other diseases, leading to the so-called Acquired Immunodeficiency Syndrome, or AIDS.
Even with the development of antiretroviral therapies that have improved quality of life and increased the life expectancy of patients with HIV/AIDS, it is widely accepted that the only way to effectively curb this devastating epidemic is through the development of an HIV-1 vaccine.

>Read more on the Brazilian Synchrotron Light Laboratory website

Image: Part of the structure of the CAP228-16H protein with the region of the V2 loop highlighted in yellow. (Full image here)

Targeting bacteria that cause meningitis and sepsis

The work provides molecular-level information about how the antibody confers broad immunity against a variable target and suggests strategies for further improvement of available vaccines.

Our central nervous systems (brain and spinal cord) are surrounded by three membranes called “meninges.” Meningitis is caused by the swelling of these membranes, resulting in headache, fever, and neck stiffness. Most cases of meningitis in the United States are the result of viral infections and are relatively mild. However, meningitis caused by bacterial infection, if left untreated, can be deadly or lead to serious complications, including hearing loss and neurologic damage.

The bacterium responsible for meningitis (Neisseria meningitidis) can also infect the bloodstream, causing another life-threatening condition known as sepsis. N. meningitidis is spread through close contact (coughing or kissing) or lengthy contact (e.g. in dorm rooms or military barracks). In this work, researchers were interested in understanding how humans develop immunity to bacterial meningitis and sepsis, collectively known as meningococcal disease, by vaccination with a new protein-based vaccine.

>Read more on the Advanced Light Source website

Image: The work provides molecular-level information about how the antibody confers broad immunity against a variable target and suggests strategies for further improvement of available vaccines.

Insights into an antibody directed against dengue virus

We are one step further to uncovering a new way to stave off dengue fever thanks to important work carried out at the I02 beamline at Diamond Light Source.

The study, recently published in Nature Immunology, describes how an antibody effectively targets the dengue virus.
Dengue virus affects hundreds of millions of people worldwide and is an untreatable infection. Secondary infections with dengue can lead to a life-threatening form of the disease due to a phenomenon called antibody-dependent enhancement (ADE). Additionally, efforts to develop a vaccine against the virus have been hindered by ADE.

A huge collaborative effort sought to investigate ADE in dengue, and two antibodies were characterised that bound to the envelope protein of the dengue virus. One of the antibodies was found to be a potent neutraliser of the virus, but importantly was unable to promote ADE.

>Read more on the Diamond Light Source website

Image: Fab binding in the context of the mature virion. e, Comparison of 2C8 Fab and 3H5 Fab docked onto a E dimer. 2C8 (green) and 3H5 (orange) Fabs were docked onto PDB ID 3J27 by aligning the EDIII potion of the structures. The Fabs are shown as surfaces and the E dimer is displayed in cartoon representation. A side view is of the E dimer on the viral surface is shown. The approximate location of the viral membrane is shown schematically.