A team led by scientists at The Scripps Research Institute (TSRI) has received a grant of more than $13 million from the National Institute of Allergy and Infectious Disease of the National Institutes of Health to study antibodies to the human immunodeficiency virus (HIV)-which will play an essential role in the creation of any effective vaccine against HIV.
Richard Wyatt, a TSRI professor of immunology and director of viral immunology for the International AIDS Vaccine Initiative’s Neutralizing Antibody Center at TSRI, will be the principal investigator for the five-year study.
“The long-term goal is to elicit broadly neutralizing antibodies against HIV,” says Wyatt. “This is a difficult task because of the variability of the virus.”
Researchers have worked toward an effective HIV vaccine since the virus was isolated in 1983, but this has been challenging because HIV’s unusual structure helps it evade the immune system and scientists’ attempts to harness the body’s defenses.
A small minority of infected people, however, do show an effective immune response to the virus. The B cells in their immune systems produce antibodies that can neutralize a wide range of HIV strains. Though this does not stop their infections from establishing in their own body, these broadly neutralizing antibodies (bNABs) do neutralize most circulating viruses and could help researchers design an effective vaccine.
This project, titled “High Resolution Analysis of Env-directed B Cells to Accelerate Vaccine Design,” will focus on generating antibodies to the virus and assessing their neutralizing capacity. Finding vaccine-elicited bNABS would be a positive step toward an effective HIV vaccine.
To be successful, Wyatt and his colleagues ultimately hope to find additional rare bNABs that can navigate some of HIV’s defensive obstacle course, determine how they do that and use that information to generate even more effective antibodies.
One of the biggest challenges for bNABs is to get past an outer layer of sugars, called glycans, which act as a “shield” to disguise the virus and block immune cells from attacking it, Wyatt says.
Another challenge is to take advantage of a stable site on the virus’s outer structure. HIV constantly mutates and changes shape, but there is one site where the virus stays the same in order to bind to a cell surface receptor protein, called CD4, present on some specialized human cells.
“The virus first has to bind to CD4, then it uses its other co-receptor to get its RNA-the genetic material-into the cell,” says Wyatt.
If Wyatt and his co-investigators can block the virus with a bNAB at that site, they could stop HIV from spreading its genetic material and establishing an infection.
To define the best means to elicit neutralizing antibodies following vaccination, Wyatt and his group are working with an international team. Co-investigators at the Karolinska Institutet in Stockholm will first immunize animals with viral surface proteins engineered in the Wyatt lab. These proteins resemble the virus, and they could prompt an immune response in the animal models. Next, the Karolinska group will analyze this immune response at the molecular level.
Wyatt’s team will then analyze the blood serum samples for the presence of neutralizing antibodies, with the ultimate goal of eliciting bNAbs.
If and when the serum analysis shows signs of elicitation of neutralizing antibodies, TSRI assistant professor Yuxing Li will lead an effort to isolate the antibodies and then use a technique called epitope mapping to see exactly how the antibodies interact with the virus. She will collaborate with researchers at TSRI and Colombia University to study the antibodies at an atomic level by using imaging techniques called electron microscopy and X-ray crystallography.
“Now is the time to really impact the field with the next generation of surface proteins, or immunogens, that induce a broadly effective immune response to HIV,” says Li.
With this information, researchers hope they will someday contribute to vaccines that stimulate a protective, virus-neutralizing response.
The number of the grant is 1P01AI104722.
Source: Scripps Research Institute
CDC Urges Vigilance: New Recommendations for Monitoring and Testing H5N1 Exposures
July 11th 2025With avian influenza A(H5N1) infections surfacing in both animals and humans, the CDC has issued updated guidance calling for aggressive monitoring and targeted testing to contain the virus and protect public health.
IP LifeLine: Layoffs and the Evolving Job Market Landscape for Infection Preventionists
July 11th 2025Infection preventionists, once hailed as indispensable during the pandemic, now face a sobering reality: budget pressures, hiring freezes, and layoffs are reshaping the field, leaving many IPs worried about their future and questioning their value within health care organizations.
A Helping Hand: Innovative Approaches to Expanding Hand Hygiene Programs in Acute Care Settings
July 9th 2025Who knew candy, UV lights, and a college kid in scrubs could double hand hygiene adherence? A Pennsylvania hospital’s creative shake-up of its infection prevention program shows that sometimes it takes more than soap to get hands clean—and keep them that way.